Evidence map›Paper›PMID 38858068›Full record

ArticleeNeuro2024

Sleep Disruption Precedes Forebrain Synaptic Tau Burden and Contributes to Cognitive Decline in a Sex-Dependent Manner in the P301S Tau Transgenic Mouse Model.

Shenée C Martin, Kathryn K Joyce, Julia S Lord, Kathryn M Harper, Viktoriya D Nikolova, Todd J Cohen, Sheryl S Moy, Graham H Diering

Abstract read
In one paragraph

Article in eNeuro, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
–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

16 citing papers in PubMed, 1 synthesis or guideline pooled it.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Shenée C MartinDepartments of Cell Biology and Physiology, Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
Kathryn K JoyceDepartments of Cell Biology and Physiology, Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.ORCID https://orcid.org/0009-0002-9227-1037
Julia S LordDepartments of Cell Biology and Physiology, Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
Kathryn M HarperPsychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
Viktoriya D NikolovaPsychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.ORCID https://orcid.org/0000-0003-0404-8602
Todd J CohenNeurology, Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.ORCID https://orcid.org/0000-0002-4099-0278
Sheryl S MoyPsychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
Graham H DieringDepartments of Cell Biology and Physiology, Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 graham_diering@med.unc.edu.ORCID https://orcid.org/0000-0001-6113-6946

Funding

Preclinical CoreP50HD103573 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI GABRIEL S DICHTER · 2020 to 2026
$9.7M
Sleep-dependent synaptic homeostasis in Alzheimer's diseaseRF1AG068063 · NIA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COHEN, TODD JONATHAN, DIERING, GRAHAM HUGH · 2021 to 2021
$2.1M
Sleep-dependent synaptic homeostasis in Alzheimer's diseaseR01AG068063 · NIA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COHEN, TODD JONATHAN, DIERING, GRAHAM HUGH · 2024 to 2025
$1.4M
Sleep-dependent synaptic homeostasis in Alzheimer's diseaseR56AG068063 · NIA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COHEN, TODD JONATHAN, DIERING, GRAHAM HUGH · 2020 to 2020
$657k
Sleep disruption in the progression and treatment of Alzheimer's diseaseF31AG074649 · NIA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MARTIN, SHENEE · 2021 to 2022
$73k
NIA NIH HHS F31 AG074649NIA NIH HHS R01 AG068063NIA NIH HHS R56 AG068063NIA NIH HHS RF1 AG068063NICHD NIH HHS P50 HD103573
6 · The paper itself

Abstract

Sleep disruption and impaired synaptic processes are common features in neurodegenerative diseases, including Alzheimer's disease (AD). Hyperphosphorylated Tau is known to accumulate at neuronal synapses in AD, contributing to synapse dysfunction. However, it remains unclear how sleep disruption and synapse pathology interact to contribute to cognitive decline. Here, we examined sex-specific onset and consequences of sleep loss in AD/tauopathy model PS19 mice. Using a piezoelectric home-cage monitoring system, we showed PS19 mice exhibited early-onset and progressive hyperarousal, a selective dark-phase sleep disruption, apparent at 3 months in females and 6 months in males. Using the Morris water maze test, we report that chronic sleep disruption (CSD) accelerated the onset of decline of hippocampal spatial memory in PS19 males only. Hyperarousal occurs well in advance of robust forebrain synaptic Tau burden that becomes apparent at 6-9 months. To determine whether a causal link exists between sleep disruption and synaptic Tau hyperphosphorylation, we examined the correlation between sleep behavior and synaptic Tau, or exposed mice to acute or chronic sleep disruption at 6 months. While we confirm that sleep disruption is a driver of Tau hyperphosphorylation in neurons of the locus ceruleus, we were unable to show any causal link between sleep loss and Tau burden in forebrain synapses. Despite the finding that hyperarousal appears earlier in females, female cognition was resilient to the effects of sleep disruption. We conclude sleep disruption interacts with the synaptic Tau burden to accelerate the onset of cognitive decline with greater vulnerability in males.

Indexed as

Cognitive DysfunctionDisease Models, AnimalMice, TransgenicProsencephalonSynapsestau ProteinsAlzheimer DiseaseAnimalsFemaleMaleMiceMice, Inbred C57BLSex CharacteristicsSleep Wake DisordersTauopathiesMapt protein, mousetau ProteinsAlzheimer's diseasebiological sexsleepsleep disruptionsynapseTau

Identifiers

PMID38858068
PMCPMC11209651

What OpenQuestion holds

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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.