Evidence map›Paper›PMID 34130857›Full record

ArticleBiological psychiatry2022

Chronic Intermittent Hypoxia Enhances Pathological Tau Seeding, Propagation, and Accumulation and Exacerbates Alzheimer-like Memory and Synaptic Plasticity Deficits and Molecular Signatures.

Syed Faraz Kazim, Abhijeet Sharma, Sivaprakasam R Saroja, Joon Ho Seo, Chloe S Larson, Aarthi Ramakrishnan, Minghui Wang, Robert D Blitzer, Li Shen, Catherine J Peña and 5 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Biological psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 2 pooled it
3.6field-weighted citation impact, top 6% 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, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.

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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

15 authors at 3 institutions in 1 country.

Syed Faraz KazimDepartment of Neurology, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Abhijeet SharmaDepartment of Neurology, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Sivaprakasam R SarojaDepartment of Neurology, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Joon Ho SeoDepartment of Neurology, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Chloe S LarsonDepartment of Neurology, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Aarthi RamakrishnanNash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Minghui WangMount Sinai Center for Transformative Disease Modeling, Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, New York.
Robert D BlitzerDepartment of Psychiatry, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Li ShenNash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Catherine J PeñaNash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
John F CraryNash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Pathology, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, New York; Neuropathology Brain Bank & Research CoRE, Icahn School of Medicine at Mount Sinai, New York, New York.
Larissa A ShimodaDepartment of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Bin ZhangMount Sinai Center for Transformative Disease Modeling, Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, New York.
Eric J NestlerNash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Ana C PereiraDepartment of Neurology, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: ana.pereira@mssm.edu.
Allen Institute for Brain Science · USIcahn School of Medicine at Mount Sinai · USJohns Hopkins University · US

Funding

Transcription Factors in Stimulant and Opioid ActionP01DA047233 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Paul J. Kenny · 2019 to 2026
$16.5M
Using neuroeconomics to disentangle the transcriptional mechanisms underlying resilience versus susceptibility to stressR01MH051399 · NIMH · YALE UNIVERSITY · PI NESTLER, ERIC J. · 1994 to 2023
$10.2M
Mechanisms of Susceptibility of Excitatory Neurons to Tau Pathology and Neurodegeneration in Alzheimer's diseaseR01AG063819 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI PEREIRA, ANA C. · 2020 to 2024
$3.9M
Mechanisms of Obstructive Sleep Apnea in Tau Pathophysiology, Risk and Progression of Alzheimer's DiseaseR01AG064020 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI PEREIRA, ANA C. · 2019 to 2023
$2.9M
Enhancing Glutamate Transport in Age-related Cognitive Decline and Alzheimer's DiseaseK76AG054772 · NIA · ROCKEFELLER UNIVERSITY · PI PEREIRA, ANA C. · 2016 to 2020
$820k
NIA NIH HHS K76 AG054772NIA NIH HHS R01 AG063819NIA NIH HHS R01 AG064020NIDA NIH HHS P01 DA047233NIMH NIH HHS R01 MH051399
6 · The paper itself

Abstract

backgroundObstructive sleep apnea, characterized by sleep fragmentation and chronic intermittent hypoxia (CIH), is a risk factor for Alzheimer's disease (AD) progression. Recent epidemiological studies point to CIH as the best predictor of developing cognitive decline and AD in older adults with obstructive sleep apnea. However, the precise underlying mechanisms remain unknown. This study was undertaken to evaluate the effect of CIH on pathological human tau seeding, propagation, and accumulation; cognition; synaptic plasticity; neuronal network excitability; and gene expression profiles in a P301S human mutant tau mouse model of AD and related tauopathies.

methodsWe exposed 4- to 4.5-month-old male P301S and wild-type mice to an 8-week CIH protocol (6-min cycle: 21% O

resultsCIH significantly enhanced pathological human tau seeding and spread across connected brain circuitry in P301S mice; it also increased phosphorylated tau load. CIH also exacerbated memory and synaptic plasticity deficits in P301S mice. However, CIH had no effect on seizure susceptibility and network hyperexcitability in these mice. Finally, CIH exacerbated AD-related pathogenic molecular signaling in P301S mice.

conclusionsCIH-induced increase in pathologic human tau seeding and spread and exacerbation of other AD-related impairments provide new insights into the role of CIH and obstructive sleep apnea in AD pathogenesis.

Indexed as

Alzheimer DiseaseTauopathiesAnimalsDisease Models, AnimalHypoxiaMaleMiceMice, Inbred C57BLMice, TransgenicNeuronal PlasticityAlzheimer’s diseaseChronic intermittent hypoxiaCognitionMolecular signaturesSynaptic plasticityTau

Identifiers

PMID34130857
PMCPMC8895475
OpenAlexW3138163199

What OpenQuestion holds

Textmetadata
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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.