Evidence map›Paper›PMID 34500400›Full record

ReviewSleep medicine reviews2021

Tau-driven degeneration of sleep- and wake-regulating neurons in Alzheimer's disease.

Caroline H Lew, Cathrine Petersen, Thomas C Neylan, Lea T Grinberg

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

Review in Sleep medicine reviews, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

55 citing papers in PubMed, 80 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. A gradual and sustainable approach to diagnosing sleep and circadian disturbances in dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  8. Characterizing circadian rest-activity rhythm patterns across Alzheimer's disease continuum in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  9. Article
  10. 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
  11. 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
  12. Article
  13. Article
  14. Transcranial near-infrared therapy restores synaptic resilience by reshaping signaling landscapes in sleep-deprived tauopathy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. 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

4 authors at 2 institutions in 2 countries.

Caroline H LewMemory and Aging Center, Weill Institute for Neurosciences, Dept. of Neurology, University of California San Francisco, CA, USA.
Cathrine PetersenMemory and Aging Center, Weill Institute for Neurosciences, Dept. of Neurology, University of California San Francisco, CA, USA; Neuroscience Graduate Program, University of California, San Francisco, CA, USA.
Thomas C NeylanMemory and Aging Center, Weill Institute for Neurosciences, Dept. of Neurology, University of California San Francisco, CA, USA; Dept. of Psychiatry, University of California, San Francisco, CA, USA.
Lea T GrinbergMemory and Aging Center, Weill Institute for Neurosciences, Dept. of Neurology, University of California San Francisco, CA, USA; Global Health Institute, University of California, San Francisco, CA, USA; Department of Pathology, University of California, San Francisco, CA, USA; Department of Pathology, University of Sao Paulo Medical School, Sao Paulo, Brazil. Electronic address: lea.grinberg@ucsf.edu.
University of California, San Francisco · USUniversidade de São Paulo · BR

Funding

Early Onset AD Consortium - the LEAD Study (LEADS)U01AG057195 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI APOSTOLOVA, LIANA G, CARRILLO, MARIA C · 2018 to 2023
$70.3M
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
NIA NIH HHS K24 AG053435NIA NIH HHS R01 AG060477NIA NIH HHS R01 AG064314NIA NIH HHS U01 AG057195
6 · The paper itself

Abstract

Disturbances of the sleep/wake cycle in Alzheimer's disease (AD) are common, frequently precede cognitive decline, and tend to worsen with disease progression. Sleep is critical to the maintenance of homeostatic and circadian function, and chronic sleep disturbances have significant cognitive and physical health consequences that likely exacerbate disease severity. Sleep-wake cycles are regulated by neuromodulatory centers located in the brainstem, the hypothalamus, and the basal forebrain, many of which are vulnerable to the accumulation of abnormal protein deposits associated with neurodegenerative conditions. In AD, while sleep disturbances are commonly attributed to the accumulation of amyloid beta, patients often first experience sleep issues prior to the appearance of amyloid beta plaques, on a timeline that more closely corresponds to the first appearance of abnormal tau neurofibrillary tangles in sleep/wake regulating areas of the brainstem. Sleep disturbances also occur in pure tauopathies, providing further support that tau is a major contributor. Here, we provide an overview of the neuroanatomy of sleep/wake centers discovered in animal models, and review the evidence that tau-driven neuropathology is a primary driver of sleep disturbance in AD.

Indexed as

Alzheimer DiseaseTauopathiesAmyloid beta-PeptidesAnimalsHumansNeuronsSleepAmyloid beta-PeptidesAlzheimer's diseaseHumanNeuropathologyProgressive supranuclear palsySleep-promotingTauopathiesWake-promoting

Identifiers

PMID34500400
PMCPMC8862638
OpenAlexW3196018552

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.