Evidence map›Paper›PMID 36642985›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2023

Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART.

Alexander J Ehrenberg, Michael A Kelberman, Kathy Y Liu, Martin J Dahl, David Weinshenker, Neus Falgàs, Shubir Dutt, Mara Mather, Mareike Ludwig, Matthew J Betts and 31 more

Open access · hybridAbstract readConsensus Statement
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
10.3field-weighted citation impact, top 1% 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

49 citing papers in PubMed, 61 citations in OpenAlex.

  1. Review
  2. Neuromodulatory subcortical systems in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  3. Article
  4. Article
  5. Stress, stress systems, and Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  6. Correlation between in vivoAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  7. Review
  8. Article
  9. Wake-promoting neuromodulators in Alzheimer's disease: Implications for sleep and brain clearance.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  10. Sex differences in neuromodulatory subcortical systems and their implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  11. The neuromodulatory fragility hypothesis of Alzheimer's disease pathogenesis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Locus coeruleus-related insula activation supports implicit learning.bioRxiv : the preprint server for biology · 2025
    Article
  20. Alpha rhythm and Alzheimer's disease: Has Hans Berger's dream come true?Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology · 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

41 authors at 20 institutions in 10 countries.

Alexander J EhrenbergMemory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
Michael A KelbermanDepartment of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
Kathy Y LiuDivision of Psychiatry, University College London, London, UK.
Martin J DahlLeonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.
David WeinshenkerDepartment of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
Neus FalgàsAlzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Shubir DuttLeonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.
Mara MatherLeonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.
Mareike LudwigInstitute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University, Magdeburg, Germany.
Matthew J BettsInstitute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University, Magdeburg, Germany.
Joseph R WinerDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
Stefan TeipelDeutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Rostock/Greifswald, Rostock, Germany.
Alexandra J WeigandSan Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, California, USA.
Oxana EschenkoDepartment of Computational Neuroscience, Max Planck Institute for Biological Cybernetics, Tuebingen, Germany.
Dorothea HämmererInstitute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University, Magdeburg, Germany.
Marina LeimanInstitute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University, Magdeburg, Germany.
Scott E CountsDepartment of Translational Neuroscience, Michigan State University, Grand Rapids, Michigan, USA.
James M ShineBrain and Mind Center, The University of Sydney, Sydney, Australia.
Ian H RobertsonGlobal Brain Health Institute, Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
Allan I LeveyGoizueta Alzheimer's Disease Research Center, Emory University, Atlanta, Georgia, USA.
Elisa LanciniInstitute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University, Magdeburg, Germany.
Gowoon SonMemory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
Christoph SchneiderGordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Maxime Van EgrooGordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Claudio LiguoriDepartment of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
Qin WangDepartment of Neuroscience and Regenerative Medicine, Medical College of Georgia, Agusta University, Agusta, Georgia, USA.
Elena M VazeyDepartment of Biology, University of Massachusetts Amherst, Amherst, Massachusetts, USA.
Federico Rodriguez-PorcelDepartment of Neurology, Medical University of South Carolina, Charleston, South Carolina, USA.
Lena HaagInstitute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University, Magdeburg, Germany.
Mark W BondiDepartment of Psychiatry, University of California, San Diego, La Jolla, California, USA.
Sven VannesteGlobal Brain Health Institute, Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
Whitney M FreezeDepartment of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
Yeo-Jin YiInstitute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University, Magdeburg, Germany.
Mihovil MaldinovDepartment of Psychiatry and Psychotherapy, University of Rostock, Rostock, Germany.
Jennifer GatchelDivision of Geriatric Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.
Abhijit SatpatiMemory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
Claudio BabiloniDepartment of Physiology and Pharmacology "V. Erspamer,", Sapienza University of Rome, Rome, Italy.
William S KremenCenter for Behavior Genetics of Aging, University of California, San Diego, La Jolla, California, USA.
Robert HowardDivision of Psychiatry, University College London, London, UK.
Heidi I L JacobsGordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Lea T GrinbergMemory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
German Center for Neurodegenerative Diseases · DEEmory University · USOtto-von-Guericke University Magdeburg · DEUniversity College London · GBUniversity of California San Diego · USUniversity of California, San Francisco · USGordon Center for Medical Imaging · USHarvard University · USTrinity College Dublin · IEUniversity of Southern California · USAugusta University · USMaastricht University · NLMax Planck Institute for Biological Cybernetics · DEMax Planck Institute for Human Development · DEMedical University of South Carolina · USMichigan State University · USSapienza University of Rome · ITStanford University · USThe University of Sydney · AUUniversitat de Barcelona · ES

Funding

TREAT AD Structural Biology CoreU54AG065187 · NIA · EMORY UNIVERSITY · PI ALLAN I LEVEY · 2019 to 2026
$69.7M
UCSD Shiley-Marcos Alzheimer's Disease Research Center P30P30AG062429 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JAMES B BREWER · 2019 to 2026
$34.9M
The Goizueta Alzheimer's Disease Research CenterP30AG066511 · NIA · EMORY UNIVERSITY · PI ALLAN I LEVEY · 2020 to 2026
$29.0M
Stanford Alzheimer's Disease Research CenterAdmin Supp: Developing iPSC models for AD and PDP30AG066515 · NIA · STANFORD UNIVERSITY · PI Lisa Goldman Rosas · 2020 to 2026
$29.0M
The VETSA Longitudinal Twin Study of Cognition and Aging (VETSA 4)R01AG050595 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ELMAN, JEREMY A, FRANZ, CAROL ELAINE · 2015 to 2024
$28.0M
Research Education ComponentP30AG072931 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Henry L Paulson · 2021 to 2026
$26.5M
South Texas Alzheimer's Disease Research CenterP30AG066546 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Sudha Seshadri · 2021 to 2026
$24.0M
Supplement to AMP-AD Brain Proteomic Network Enhancement, Validation and Translation into CSF BiomarkersU01AG061357 · NIA · EMORY UNIVERSITY · PI LEVEY, ALLAN I, SEYFRIED, NICHOLAS THOMAS · 2018 to 2022
$9.1M
The VETSA Longitudinal MRI Twin Study of Aging (VETSA MRI 4)R01AG076838 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ANDERS M DALE, Jeremy A Elman · 2022 to 2026
$8.7M
Clinical Features and Neuropathological Basis of Sleep Wake Behavior in Alzheimer's and PSPR01AG060477 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Lea Tenenholz Grinberg, Thomas C Neylan · 2019 to 2026
$8.2M
The Impact of Emotional Regulation on Cognition in AgingR01AG025340 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MATHER, MARA · 2004 to 2021
$7.9M
Tracking the origin of tau pathology: dovetailing (pre-)preclinical biomarker trajectoriesR01AG062559 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Heidi Irma Jacobs · 2019 to 2026
$4.8M
Medical Research Council MR/S021418/1NIAAA NIH HHS U01 AA025481NIA NIH HHS F31 AG069502NIA NIH HHS F32 AG074625NIA NIH HHS K23 AG058805NIA NIH HHS K24 AG053435NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG066511NIA NIH HHS P30 AG066515NIA NIH HHS P30 AG066546NIA NIH HHS P30 AG072931NIA NIH HHS R01 AG025340NIA NIH HHS R01 AG050595NIA NIH HHS R01 AG060477NIA NIH HHS R01 AG060731NIA NIH HHS R01 AG062559NIA NIH HHS R01 AG062581NIA NIH HHS R01 AG064314NIA NIH HHS R01 AG064664NIA NIH HHS R01 AG068062NIA NIH HHS R01 AG070826NIA NIH HHS R01 AG076838NIA NIH HHS R01 AG078191NIA NIH HHS R21 AG074220NIA NIH HHS RF1 AG056573NIA NIH HHS RF1 AG056815NIA NIH HHS RF1 AG061175NIA NIH HHS RF1 AG067729NIA NIH HHS U01 AG061357NIA NIH HHS U54 AG065187NIGMS NIH HHS T32 GM139780
6 · The paper itself

Abstract

The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau-associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD. Experimental studies even suggest that AD-associated NSS degeneration drives brain neuroinflammatory status and contributes to disease progression, including the exacerbation of cortical lesions. Given the important pathophysiologic and etiologic roles that involve the NSS in early AD stages, there is an urgent need to expand our understanding of the mechanisms underlying NSS vulnerability and more precisely detail the clinical progression of NSS changes in AD. Here, the NSS Professional Interest Area of the International Society to Advance Alzheimer's Research and Treatment highlights knowledge gaps about NSS within AD and provides recommendations for priorities specific to clinical research, biomarker development, modeling, and intervention. HIGHLIGHTS: Neuromodulatory nuclei degenerate in early Alzheimer's disease pathological stages. Alzheimer's pathophysiology is exacerbated by neuromodulatory nuclei degeneration. Neuromodulatory nuclei degeneration drives neuropsychiatric symptoms in dementia. Biomarkers of neuromodulatory integrity would be value-creating for dementia care. Neuromodulatory nuclei present strategic prospects for disease-modifying therapies.

Indexed as

Alzheimer DiseaseBiomarkersBrainDisease ProgressionHumansBiomarkers

Identifiers

PMID36642985
PMCPMC10182252
OpenAlexW4316371712

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Registered trials

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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.