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ArticleNeurology2024

Fluid Biomarkers in Individuals at Risk for Genetic Prion Disease up to Disease Conversion.

Sonia M Vallabh, Meredith A Mortberg, Shona W Allen, Ashley C Kupferschmid, Pia Kivisakk, Bruno L Hammerschlag, Anna Bolling, Bianca A Trombetta, Kelli Devitte-McKee, Abaigeal M Ford and 7 more

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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 NCT05124392 (OBSERVE), which is not on this map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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.

NCT05124392 recruitingnot on this map

OBSERVE: Biomarkers in Individuals at Risk for Prion Disease

Typeobservational_patient_registrySponsorMassachusetts General HospitalRan2017 to 2027Enrolled150ConditionsCJD (Creutzfeldt Jakob Disease), Prion Diseases, GSS, FFI
3 · Its place in the literature

Who cites it

11 citing papers in PubMed.

  1. Mortality of Individuals WithNeurology. Genetics · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Sonia M VallabhFrom the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.ORCID 0000-0003-3824-2702
Meredith A MortbergFrom the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.
Shona W AllenFrom the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.
Ashley C KupferschmidFrom the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.
Pia KivisakkFrom the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.
Bruno L HammerschlagFrom the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.
Anna BollingFrom the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.
Bianca A TrombettaFrom the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.
Kelli Devitte-McKeeFrom the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.
Abaigeal M FordFrom the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.
Lauren E SatherFrom the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.
Griffin DuffyFrom the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.
Ashley RiveraFrom the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.
Jessica GerberFrom the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.
Alison J McManusFrom the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.
Eric V MinikelFrom the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.ORCID 0000-0003-2206-1608
Steven E ArnoldFrom the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.ORCID 0000-0002-9487-415X

Funding

Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Christine S Ritchie · 2019 to 2026
$36.5M
NIA NIH HHS P30 AG062421
6 · The paper itself

Abstract

objectivesTo longitudinally characterize disease-relevant CSF and plasma biomarkers in individuals at risk for genetic prion disease up to disease conversion.

methodsThis single-center longitudinal cohort study has followed known carriers of

resultsAmong 41 carriers and 21 controls enrolled, 28 (68%) and 15 (71%) were female, and mean ages were 47.5 and 46.1. At baseline, all individuals were asymptomatic. We observed RT-QuIC seeding activity in the CSF of 3 asymptomatic E200K carriers who subsequently converted to symptomatic and died of prion disease. 1 P102L carrier remained RT-QuIC negative through symptom conversion. No other individuals developed symptoms. The prodromal window from detection of RT-QuIC positivity to disease onset was 1 year long in an E200K individual homozygous (V/V) at PRNP codon 129 and 2.5 and 3.1 years in 2 codon 129 heterozygotes (M/V). Changes in neurodegenerative and neuroinflammatory markers were variably observed prior to onset, with increases observed for plasma NfL in 4/4 converters, and plasma GFAP, CSF NfL, CSF T-tau, and CSF beta-synuclein each in 2/4 converters, although values relative to age and fold changes relative to individual baseline were not remarkable for any of these markers. CSF PrP was longitudinally stable with mean coefficient of variation 9.0% across all individuals over up to 6 years, including data from converting individuals at RT-QuIC-positive timepoints. DISCUSSION: CSF prion seeding activity may represent the earliest detectable prodromal sign in E200K carriers. Neuronal damage and neuroinflammation markers show limited sensitivity in the prodromal phase. CSF PrP levels remain stable even in the presence of RT-QuIC seeding activity. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT05124392 posted 2017-12-01, updated 2023-01-27.

Indexed as

BiomarkersPrion DiseasesPrion ProteinsAdultalpha-SynucleinDisease ProgressionFemaleGlial Fibrillary Acidic ProteinHeterozygoteHumansLongitudinal StudiesMaleMiddle AgedNeurofilament Proteinstau Proteinsalpha-SynucleinBiomarkersGFAP protein, humanGlial Fibrillary Acidic Proteinneurofilament protein LNeurofilament ProteinsPrion ProteinsPRNP protein, humantau Proteins

Identifiers

PMID38896810
PMCPMC11226308

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