Evidence map›Paper›PMID 37491329›Full record

ArticleNeurology2023

Association of Novelty-Related Locus Coeruleus Function With Entorhinal Tau Deposition and Memory Decline in Preclinical Alzheimer Disease.

Prokopis C Prokopiou, Nina Engels-Domínguez, Aaron P Schultz, Jorge Sepulcre, Elouise A Koops, Kathryn V Papp, Gad A Marshall, Marc D Normandin, Georges El Fakhri, Dorene Rentz and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Sex and life experience shape locus coeruleus pretangle tau pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  5. Resistance and resilience to Alzheimer's disease in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
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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

13 authors at 1 institution in 2 countries.

Prokopis C ProkopiouFrom the Gordon Center for Medical Imaging (P.C.P., N.E.-D., J.S., E.A.K., M.D.N., G.E.F., K.A.J., H.I.L.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Faculty of Health (N.E.-D., H.I.L.J.), Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, The Netherlands; Department of Neurology (A.P.S., K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Massachusetts General Hospital, Harvard Medical School; The Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School; and Center for Alzheimer Research and Treatment (K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-5444-8359
Nina Engels-DomínguezFrom the Gordon Center for Medical Imaging (P.C.P., N.E.-D., J.S., E.A.K., M.D.N., G.E.F., K.A.J., H.I.L.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Faculty of Health (N.E.-D., H.I.L.J.), Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, The Netherlands; Department of Neurology (A.P.S., K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Massachusetts General Hospital, Harvard Medical School; The Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School; and Center for Alzheimer Research and Treatment (K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-1896-7960
Aaron P SchultzFrom the Gordon Center for Medical Imaging (P.C.P., N.E.-D., J.S., E.A.K., M.D.N., G.E.F., K.A.J., H.I.L.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Faculty of Health (N.E.-D., H.I.L.J.), Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, The Netherlands; Department of Neurology (A.P.S., K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Massachusetts General Hospital, Harvard Medical School; The Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School; and Center for Alzheimer Research and Treatment (K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Jorge SepulcreFrom the Gordon Center for Medical Imaging (P.C.P., N.E.-D., J.S., E.A.K., M.D.N., G.E.F., K.A.J., H.I.L.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Faculty of Health (N.E.-D., H.I.L.J.), Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, The Netherlands; Department of Neurology (A.P.S., K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Massachusetts General Hospital, Harvard Medical School; The Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School; and Center for Alzheimer Research and Treatment (K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-4199-2304
Elouise A KoopsFrom the Gordon Center for Medical Imaging (P.C.P., N.E.-D., J.S., E.A.K., M.D.N., G.E.F., K.A.J., H.I.L.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Faculty of Health (N.E.-D., H.I.L.J.), Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, The Netherlands; Department of Neurology (A.P.S., K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Massachusetts General Hospital, Harvard Medical School; The Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School; and Center for Alzheimer Research and Treatment (K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-4105-4254
Kathryn V PappFrom the Gordon Center for Medical Imaging (P.C.P., N.E.-D., J.S., E.A.K., M.D.N., G.E.F., K.A.J., H.I.L.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Faculty of Health (N.E.-D., H.I.L.J.), Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, The Netherlands; Department of Neurology (A.P.S., K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Massachusetts General Hospital, Harvard Medical School; The Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School; and Center for Alzheimer Research and Treatment (K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Gad A MarshallFrom the Gordon Center for Medical Imaging (P.C.P., N.E.-D., J.S., E.A.K., M.D.N., G.E.F., K.A.J., H.I.L.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Faculty of Health (N.E.-D., H.I.L.J.), Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, The Netherlands; Department of Neurology (A.P.S., K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Massachusetts General Hospital, Harvard Medical School; The Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School; and Center for Alzheimer Research and Treatment (K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Marc D NormandinFrom the Gordon Center for Medical Imaging (P.C.P., N.E.-D., J.S., E.A.K., M.D.N., G.E.F., K.A.J., H.I.L.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Faculty of Health (N.E.-D., H.I.L.J.), Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, The Netherlands; Department of Neurology (A.P.S., K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Massachusetts General Hospital, Harvard Medical School; The Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School; and Center for Alzheimer Research and Treatment (K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0001-9239-2600
Georges El FakhriFrom the Gordon Center for Medical Imaging (P.C.P., N.E.-D., J.S., E.A.K., M.D.N., G.E.F., K.A.J., H.I.L.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Faculty of Health (N.E.-D., H.I.L.J.), Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, The Netherlands; Department of Neurology (A.P.S., K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Massachusetts General Hospital, Harvard Medical School; The Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School; and Center for Alzheimer Research and Treatment (K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-9005-6993
Dorene RentzFrom the Gordon Center for Medical Imaging (P.C.P., N.E.-D., J.S., E.A.K., M.D.N., G.E.F., K.A.J., H.I.L.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Faculty of Health (N.E.-D., H.I.L.J.), Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, The Netherlands; Department of Neurology (A.P.S., K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Massachusetts General Hospital, Harvard Medical School; The Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School; and Center for Alzheimer Research and Treatment (K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-6318-9213
Reisa A SperlingFrom the Gordon Center for Medical Imaging (P.C.P., N.E.-D., J.S., E.A.K., M.D.N., G.E.F., K.A.J., H.I.L.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Faculty of Health (N.E.-D., H.I.L.J.), Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, The Netherlands; Department of Neurology (A.P.S., K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Massachusetts General Hospital, Harvard Medical School; The Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School; and Center for Alzheimer Research and Treatment (K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Keith A JohnsonFrom the Gordon Center for Medical Imaging (P.C.P., N.E.-D., J.S., E.A.K., M.D.N., G.E.F., K.A.J., H.I.L.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Faculty of Health (N.E.-D., H.I.L.J.), Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, The Netherlands; Department of Neurology (A.P.S., K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Massachusetts General Hospital, Harvard Medical School; The Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School; and Center for Alzheimer Research and Treatment (K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Heidi I L JacobsFrom the Gordon Center for Medical Imaging (P.C.P., N.E.-D., J.S., E.A.K., M.D.N., G.E.F., K.A.J., H.I.L.J.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Faculty of Health (N.E.-D., H.I.L.J.), Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, The Netherlands; Department of Neurology (A.P.S., K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Massachusetts General Hospital, Harvard Medical School; The Athinoula A. Martinos Center for Biomedical Imaging (A.P.S.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School; and Center for Alzheimer Research and Treatment (K.V.P., G.A.M., D.R., R.A.S., K.A.J.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. hjacobs@mgh.harvard.edu.ORCID 0000-0001-7620-3822
Brigham and Women's Hospital · US

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
RECRUITMENT COREU19AG010483 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FELDMAN, HOWARD · 2013 to 2020
$80.6M
Vascular factors, physical activity, and inflammation as modulators of neurodegenerative and cognitive trajectories (Project 2)P01AG036694 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Rachel Frances Buckley, Keith A. Johnson · 2010 to 2026
$50.2M
THE ROLE OF ADVANCED CAA IN ALZHEIMER'S DEMENTIAP50AG005134 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HYMAN, BRADLEY T. · 1985 to 2018
$42.1M
Unified Joint Statistical Reconstruction of PET & MRP41EB022544 · NIBIB · YALE UNIVERSITY · PI Kira Grogg · 2017 to 2026
$14.8M
Project 4P41EB015896 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI ROSEN, BRUCE R · 2012 to 2018
$9.8M
Evolution of memory-related fMRI activation over the course of MCI and ADR01AG027435 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI JOHNSON, KEITH A., SPERLING, REISA A. · 2006 to 2016
$8.6M
Vascular Dysfunction in Cerebral Amyloid AngiopathyR01AG026484 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI GREENBERG, STEVEN M · 2005 to 2019
$7.5M
Imaging CoreU01AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2008 to 2009
$6.1M
Tracking the origin of tau pathology: dovetailing (pre-)preclinical biomarker trajectoriesR01AG062559 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Heidi Irma Jacobs · 2019 to 2026
$4.8M
The wandering nerve: gateway to boost Alzheimer's disease related cognitive performanceR01AG068062 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI JACOBS, HEIDI IRMA · 2021 to 2025
$4.6M
Novel automated performance-based ADL outcomes for early AD clinical trialsR01AG053184 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI MARSHALL, GAD ASHER · 2018 to 2023
$4.5M
NCRR NIH HHS S10 RR019307NCRR NIH HHS S10 RR023043NCRR NIH HHS S10 RR023401NIA NIH HHS K23 AG053422NIA NIH HHS K24 AG035007NIA NIH HHS P50 AG005134NIA NIH HHS R01 AG026484NIA NIH HHS R01 AG027435NIA NIH HHS R01 AG034556NIA NIH HHS R01 AG037497NIA NIH HHS R01 AG053184NIA NIH HHS R01 AG061445NIA NIH HHS R01 AG061811NIA NIH HHS R01 AG067021NIA NIH HHS R01 AG071074NIA NIH HHS R21 AG038994NIA NIH HHS R21 AG064413NIA NIH HHS R21 AG070877NIA NIH HHS R42 AG069629NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG032438NIA NIH HHS U19 AG010483NIBIB NIH HHS P41 EB015896NIBIB NIH HHS R01 EB014894NIH HHS S10 OD010364NIH HHS S10 OD018035
6 · The paper itself

Abstract

BACKGROUND AND

objectivesThe predictable Braak staging scheme suggests that cortical tau progression may be related to synaptically connected neurons. Animal and human neuroimaging studies demonstrated that changes in neuronal activity contribute to tau spreading. Whether similar mechanisms explain tau progression from the locus coeruleus (LC), a tiny noradrenergic brainstem nucleus involved in novelty, learning, and memory and among the earliest regions to accumulate tau, has not yet been established. We aimed to investigate whether novelty-related LC activity was associated with the accumulation of cortical tau and its implications for cognitive decline.

methodsWe combined functional MRI data of a novel vs repeated face-name learning paradigm, [

resultsThe participants' average age at baseline was 69.67 ± 10.14 years. Fifty-one participants were female. Ninety-one participants were cognitively normal (CDR global = 0), and one participant had mild cognitive impairment (CDR global = 0.5) at baseline. Lower novelty-related LC activity was specifically related to greater tau deposition in the medial-lateral temporal cortex and steeper memory decline. LC activity during novelty vs repetition was not related to executive dysfunction or decline on the PACC5. The relationship between LC activity and memory decline was partially mediated by EC tau, particularly in individuals with elevated beta-amyloid deposition. DISCUSSION: Our results suggested that lower novelty-related LC activity is associated with the emergence of EC tau and that the downstream effects of this LC-EC pathway on memory decline also require the presence of elevated beta-amyloid. Longitudinal studies are required to investigate whether optimal LC activity has the potential to delay tau spread and memory decline, which may have implications for designing targeted interventions promoting resilience.

Indexed as

Alzheimer DiseaseCognitive DysfunctionAgedAmyloid beta-PeptidesAnimalsFemaleHumansLocus CoeruleusMaleMemory DisordersMiddle AgedPositron-Emission Tomographytau ProteinsAmyloid beta-Peptidestau Proteins

Identifiers

PMID37491329
PMCPMC10516269
OpenAlexW4385235555

What OpenQuestion holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.