Evidence map›Paper›PMID 41810694›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026

Zolpidem restores sleep and decreases amyloid in a mouse model.

Lu Yu, Shinya Yokomizo, Tri H Doan, Qiuchen Zhao, Akshatha Ganne, Meenakshisundaram Balasubramaniam, Ksenia V Kastanenka

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Lu YuDepartment of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Mass General Brigham and Harvard Medical School, Charlestown, Massachusetts, USA.
Shinya YokomizoDepartment of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Mass General Brigham and Harvard Medical School, Charlestown, Massachusetts, USA.ORCID 0000-0003-4096-9695
Tri H DoanDepartment of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Mass General Brigham and Harvard Medical School, Charlestown, Massachusetts, USA.
Qiuchen ZhaoDepartment of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Mass General Brigham and Harvard Medical School, Charlestown, Massachusetts, USA.
Akshatha GanneDepartment of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Meenakshisundaram BalasubramaniamDepartment of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Ksenia V KastanenkaDepartment of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Mass General Brigham and Harvard Medical School, Charlestown, Massachusetts, USA.ORCID 0000-0002-3727-0317

Funding

Elucidating circuit disruptions in Alzheimer's diseaseR01AG066171 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI KASTANENKA, KSENIA V. · 2020 to 2024
$2.9M
Affiliated Hospital of Xuzhou Medical University PYJH2024314BrightFocus FoundationChan Zuckerberg Initiative DAF FundCure Alzheimer's FundJapan Society for the Promotion of Science 202360054NIA NIH HHS R01 AG066171NIH HHS R01AG066171
6 · The paper itself

Abstract

introductionDeficits in non-rapid eye movement (NREM) sleep facilitate Alzheimer's disease (AD) progression. Enhancing gamma-aminobutyric acid-ergic (GABAergic) signaling can restore sleep. Unbiased computational analysis identified zolpidem as high-affinity GABA receptor modulator facilitating chloride transport that could slow AD.

methodsZolpidem's effects on sleep and Alzheimer's progression were evaluated in young APP/PS1 (amyloid precursor protein/presenilin 1) mice. Sleep was monitored with electroencephalography/electromyography (EEG/EMG) telemetry. Wide-field imaging with voltage-sensitive dyes (VSDs) was used to track sleep-dependent brain rhythms. Multiphoton microscopy allowed assessments of amyloid plaque load and basal neuronal calcium levels. Behavioral assays were used to measure memory and cognitive function.

resultsZolpidem restored NREM sleep and rescued sleep-dependent brain rhythm, slow oscillation. Zolpidem administration reduced cortical amyloid plaque burden, mitigated neuronal calcium overload, and enhanced sleep-dependent contextual recall without adverse effects on locomotion. DISCUSSION: Zolpidem effectively decreased amyloid in young APP/PS1 mice. This supports zolpidem's therapeutic promise as an intervention strategy at early stages of AD. HIGHLIGHTS: Zolpidem treatment improves non-rapid eye movement (NREM) sleep stability and reduces sleep fragmentation. Zolpidem restores slow oscillation in young APP/PS1 (amyloid precursor protein/presenilin 1) mice. Zolpidem treatment reduces amyloid plaque burden and calcium overload in neurons. Zolpidem-treated mice show improved sleep-dependent memory consolidation. Sleep rhythm enhancement shows promise for Alzheimer's therapy.

Indexed as

Alzheimer DiseasePlaque, AmyloidPyridinesSleepZolpidemAmyloid beta-Protein PrecursorAnimalsBrainDisease Models, AnimalElectroencephalographyMaleMiceMice, TransgenicPresenilin-1Amyloid beta-Protein PrecursorPresenilin-1PyridinesZolpidemAlzheimer's diseaseamyloid plaquesAPP/PS1 micecalcium homeostasisGABAA receptormemory consolidationneurodegenerationNREM sleepsleepslow oscillationzolpidem

Identifiers

PMID41810694
PMCPMC12976976

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.