Evidence map›Paper›PMID 38959435›Full record

ArticleNeurology2024

CSF Proteomics in Patients With Progressive Supranuclear Palsy.

Amy Wise, Jingyao Li, Mai Yamakawa, Joseph Loureiro, Brant Peterson, Kathleen Worringer, Rajeev Sivasankaran, Jose-Alberto Palma, Laura Mitic, Hilary W Heuer and 22 more

Registry-linked trialAbstract read

PubMed Full text at PMC Publisher

In one paragraph

Article in Neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02966145 (The Four-Repeat Tauopathy Neuroimaging Initiative), which is not on this map. Cited by 9 papers.

0numbers the graph read from it

0cells of the map it votes in

9citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02966145 completednot on this map

The Four-Repeat Tauopathy Neuroimaging Initiative

TypeobservationalSponsorUniversity of California, San FranciscoRan2016 to 2024Enrolled293ConditionsCorticobasal Degeneration (CBD), Corticobasal Syndrome (CBS), Cortical-basal Ganglionic Degeneration (CBGD), Progressive Supranuclear Palsy (PSP)ArmsObservational Study

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

The Possible Significance of Proteomics in Understanding Molecular Mechanisms of Progressive Supranuclear Palsy, Corticobasal Degeneration, Multiple System Atrophy, and Dementia with Lewy Bodies.Cells · 2026
Review
Rapidly progressive dysphagia and vertical supranuclear gaze palsy: a key diagnostic clue for progressive supranuclear palsy in Levodopa-Resistant parkinsonism.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
Article
Spilling the T: T cells in tauopathy mechanisms, disease progression, and therapeutic horizons.Molecular neurodegeneration advances · 2026
Review
Diagnostic utility of biomarkers in progressive supranuclear palsy: toward a biotyping framework.Journal of neurology · 2025
Review
Large-scale CSF proteome profiling identifies biomarkers for accurate diagnosis of frontotemporal dementia.Molecular neurodegeneration · 2025
Article
Midbrain cytotoxic T cells as a distinct neuropathological feature of progressive supranuclear palsy.Brain : a journal of neurology · 2025
Article
Interrogating the plasma proteome of repetitive head impact exposure and chronic traumatic encephalopathy.Molecular neurodegeneration · 2025
Article
Differentiating Progressive Supranuclear Palsy and Corticobasal Syndrome: Insights from Cerebrospinal Fluid Biomarkers-A Narrative Review.Medicina (Kaunas, Lithuania) · 2025
Review
Progression and natural history of Atypical Parkinsonism (ATPARK): Protocol for a longitudinal follow-up study from an underrepresented population.PloS one · 2025
Article

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

32 authors.

Amy WiseFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.

Jingyao LiFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.

Mai YamakawaFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.

Joseph LoureiroFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.

Brant PetersonFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.

Kathleen WorringerFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.

Rajeev SivasankaranFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.

Jose-Alberto PalmaFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.

Laura MiticFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.ORCID 0009-0005-5233-1674

Hilary W HeuerFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.ORCID 0000-0002-3776-1685

Argentina Lario-LagoFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.

Adam M StaffaroniFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.ORCID 0000-0002-3903-9805

Annie ClarkFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.

Jack TaylorFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.

Peter A LjubenkovFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.

Lawren VandevredeFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.ORCID 0000-0002-8304-6711

Lea T GrinbergFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.ORCID 0000-0002-6809-0618

Salvatore SpinaFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.ORCID 0000-0003-3570-9143

William W SeeleyFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.ORCID 0000-0003-1410-2027

Bruce L MillerFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.ORCID 0000-0002-2152-4220

Bradley F BoeveFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.ORCID 0000-0002-4153-8187

Bradford C DickersonFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.ORCID 0000-0002-5958-3445

Murray GrossmanFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.

Irene LitvanFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.ORCID 0000-0002-3485-3445

Alexander PantelyatFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.ORCID 0000-0002-6427-7485

Maria Carmela TartagliaFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.ORCID 0000-0002-5944-8497

Zihan ZhangFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.

Anne-Marie A WillsFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.ORCID 0000-0002-0901-4711

Jessica RexachFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.

Julio C RojasFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.

Adam L BoxerFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.

as the 4-Repeat Tauopathy Neuroimaging InitiativeFrom the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.

Funding

Research Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI MARILYN S. ALBERT · 2020 to 2026

$29.3M

Translational Epidemiology - Training for Research on Aging and Chronic diseaseT32AG049663 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Elizabeth Rose Mayeda, Mark J Pletcher · 2016 to 2026

$5.8M

BIOMARKER DISCOVERY AND VALIDATION IN PSPU01NS102035 · NINDS · JOHNS HOPKINS UNIVERSITY · PI PANTELYAT, ALEXANDER Y. · 2018 to 2022

$4.5M

Single cell and tissue level functional genomic analysis of astrocyte-related mechanisms in tauopathyK08NS105916 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REXACH, JESSICA E · 2019 to 2023

$1.1M

Multi-modal magnetic resonance imaging in progressive supranuclear palsy (PSP)K23AG059891 · NIA · JOHNS HOPKINS UNIVERSITY · PI PANTELYAT, ALEXANDER Y. · 2018 to 2022

$968k

Optimizing Clinical Trial Endpoints in Frontotemporal DementiaK23AG061253 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STAFFARONI, ADAM MARK · 2019 to 2023

$946k

NIA NIH HHS K23 AG059891NIA NIH HHS K23 AG061253NIA NIH HHS P30 AG066507NIA NIH HHS T32 AG049663NINDS NIH HHS K08 NS105916NINDS NIH HHS U01 NS102035

6 · The paper itself

Abstract

BACKGROUND AND

objectivesIdentification of fluid biomarkers for progressive supranuclear palsy (PSP) is critical to enhance therapeutic development. We implemented unbiased DNA aptamer (SOMAmer) proteomics to identify novel CSF PSP biomarkers.

methodsThis is a cross-sectional study in original (18 clinically diagnosed PSP-Richardson syndrome [PSP-RS], 28 cognitively healthy controls]), validation (23 PSP-RS, 26 healthy controls), and neuropathology-confirmed (21 PSP, 52 non-PSP frontotemporal lobar degeneration) cohorts. Participants were recruited through the University of California, San Francisco, and the 4-Repeat Neuroimaging Initiative. The original and neuropathology cohorts were analyzed with the SomaScan platform version 3.0 (5026-plex) and the validation cohort with version 4.1 (7595-plex). Clinical severity was measured with the PSP Rating Scale (PSPRS). CSF proteomic data were analyzed to identify differentially expressed targets, implicated biological pathways using enrichment and weighted consensus gene coexpression analyses, diagnostic value of top targets with receiver-operating characteristic curves, and associations with disease severity with linear regressions.

resultsA total of 136 participants were included (median age 70.6 ± 8 years, 68 [50%] women). One hundred fifty-five of 5,026 (3.1%), 959 of 7,595 (12.6%), and 321 of 5,026 (6.3%) SOMAmers were differentially expressed in PSP compared with controls in original, validation, and neuropathology-confirmed cohorts, with most of the SOMAmers showing reduced signal (83.1%, 95.1%, and 73.2%, respectively). Three coexpression modules were associated with PSP across cohorts: (1) synaptic function/JAK-STAT (β = -0.044, corrected DISCUSSION: Axon guidance pathway proteins and several other molecular pathways are downregulated in PSP, compared with controls. Proteins in these pathways may be useful targets for biomarker or therapeutic development.

Indexed as

BiomarkersProteomicsSupranuclear Palsy, ProgressiveAgedAged, 80 and overCohort StudiesCross-Sectional StudiesFemaleHumansMaleMiddle AgedBiomarkers

Identifiers

PMID38959435

DOI10.1212/WNL.0000000000209585

PMCPMC11226322

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NCT02966145ClinicalTrials.gov

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