Evidence map›Paper›PMID 31416793›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2019

Profound degeneration of wake-promoting neurons in Alzheimer's disease.

Jun Oh, Rana A Eser, Alexander J Ehrenberg, Dulce Morales, Cathrine Petersen, Jessica Kudlacek, Sara R Dunlop, Panos Theofilas, Elisa D P F Resende, Celica Cosme and 9 more

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

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed, 1 pooled it
7.7field-weighted citation impact, top 2% 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

89 citing papers in PubMed, 1 synthesis or guideline pooled it, 134 citations in OpenAlex.

  1. Tracking electrophysiological signatures of Alzheimer's disease: a systematic review of multimodal studies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Pooled it
  2. Trial
  3. Trial
  4. Article
  5. Article
  6. Article
  7. Review
  8. Sleep fragmentation correlates with amyloid beta deposition at brain autopsy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  9. Hypothalamic MCH neurons links tau pathology to sleep disruption.bioRxiv : the preprint server for biology · 2026
    Article
  10. Stress, stress systems, and Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  11. Night-to-night rapid eye movement sleep variability: A relevant marker of early amyloid-β deposition.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Observational
  12. 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
  13. Article
  14. 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
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

29 more citing papers are in PubMed but not listed here.

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

19 authors at 5 institutions in 4 countries.

Jun OhMemory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Rana A EserMemory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Alexander J EhrenbergMemory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA; Department of Integrative Biology, University of California, Berkeley, Berkeley, CA, USA.
Dulce MoralesMemory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Cathrine PetersenMemory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Jessica KudlacekMemory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Sara R DunlopMemory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, Northwestern University, Chicago, IL, USA.
Panos TheofilasMemory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Elisa D P F ResendeMemory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Global Brain Health Institute, University of California, San Francisco, San Francisco, CA, USA.
Celica CosmeMemory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Eduardo J L AlhoDepartment of Neurology, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Salvatore SpinaMemory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Christine M WalshMemory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Bruce L MillerMemory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Global Brain Health Institute, University of California, San Francisco, San Francisco, CA, USA.
William W SeeleyMemory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Jackson C BittencourtDepartment of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil; Center for Neuroscience and Behavior, Institute of Psychology, University of Sao Paulo, Sao Paulo, Brazil.
Thomas C NeylanDepartment of Psychiatry, University of California, San Francisco, San Francisco, CA, USA.
Helmut HeinsenDepartment of Pathology, University of Sao Paulo Medical School, Sao Paulo, Brazil; Department of Psychiatry, University of Wuerzburg, Wuerzburg, Germany.
Lea T GrinbergMemory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Global Brain Health Institute, University of California, San Francisco, San Francisco, CA, USA; Department of Pathology, University of Sao Paulo Medical School, Sao Paulo, Brazil; Department of Pathology, University of California, San Francisco, San Francisco, CA, USA. Electronic address: lea.grinberg@ucsf.edu.
University of California, San Francisco · USUniversidade de São Paulo · BRGlobal Brain Health Institute · USUniversity of California, Berkeley · USInstitute of Biomedical Science · GB

Funding

TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
Research Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Serggio Carlo Lanata · 2019 to 2026
$36.9M
PrPSc SPECIFIC INTERACTION WITH NOVEL PrP-Fc FUSION PROTEINSP50AG023501 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MILLER, BRUCE L · 2004 to 2018
$27.1M
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
Linking Sleep Dysfunction to Tau-related Degeneration across AD ProgressionR01AG064314 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRINBERG, LEA TENENHOLZ, NEYLAN, THOMAS C · 2019 to 2023
$4.0M
Neuropathological changes underlying clinical heterogeneity in Alzheimer diseaseK24AG053435 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRINBERG, LEA TENENHOLZ · 2016 to 2025
$1.8M
Neuropathological basis of brain network dysfunctionK08AG052648 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SPINA, SALVATORE · 2016 to 2020
$852k
NIA NIH HHS K08 AG052648NIA NIH HHS K24 AG053435NIA NIH HHS P01 AG019724NIA NIH HHS P30 AG062422NIA NIH HHS P50 AG023501NIA NIH HHS R01 AG060477NIA NIH HHS R01 AG064314
6 · The paper itself

Abstract

introductionSleep-wake disturbances are a common and early feature in Alzheimer's disease (AD). The impact of early tau pathology in wake-promoting neurons (WPNs) remains unclear.

methodsWe performed stereology in postmortem brains from AD individuals and healthy controls to identify quantitative differences in morphological metrics in WPNs. Progressive supranuclear palsy (PSP) and corticobasal degeneration were included as disease-specific controls.

resultsThe three nuclei studied accumulate considerable amounts of tau inclusions and showed a decrease in neurotransmitter-synthetizing neurons in AD, PSP, and corticobasal degeneration. However, substantial neuronal loss was exclusively found in AD. DISCUSSION: WPNs are extremely vulnerable to AD but not to 4 repeat tauopathies. Considering that WPNs are involved early in AD, such degeneration should be included in the models explaining sleep-wake disturbances in AD and considered when designing a clinical intervention. Sparing of WPNs in PSP, a condition featuring hyperinsomnia, suggest that interventions to suppress the arousal system may benefit patients with PSP.

Indexed as

AgedAlzheimer DiseaseAutopsyBrainFemaleHumansMaleMiddle AgedNeuronsSleep Wake DisordersSupranuclear Palsy, ProgressiveTauopathiesAlzheimer's diseaseAutopsyCorticobasal degenerationHistamineHumanLocus coeruleusOrexinProgressive supranuclear palsySleepTauopathiesUnbiased stereologyWakefulnessWake-promoting

Identifiers

PMID31416793
PMCPMC6801040
OpenAlexW2968114260

What OpenQuestion holds

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Registered trials

None linked

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.