Evidence map›Paper›PMID 41804725›Full record

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

Sex and life experience shape locus coeruleus pretangle tau pathology.

Zia Hasan, Sarah E Torraville, Tamunotonye Omoluabi, Aida Maziar, Onyedikachi N Belolise, Lauren A MacGowan, Cassandra M Flynn, Camila Reinhardt, Susan G Walling, Touati Benoukraf and 1 more

Abstract read
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

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

11 authors.

Zia HasanBiomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
Sarah E TorravilleBiomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
Tamunotonye OmoluabiBiomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
Aida MaziarBiomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
Onyedikachi N BeloliseBiomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
Lauren A MacGowanBiomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
Cassandra M FlynnBiomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
Camila ReinhardtBiomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
Susan G WallingDepartment of Psychology, Faculty of Science, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
Touati BenoukrafBiomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
Qi YuanBiomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.ORCID 0000-0002-9837-8495

Funding

Alzheimer Society of Canada New Investigator Grant #20-04Canadian Institutes of Health Research Project Grant #PJT-169197
6 · The paper itself

Abstract

introductionAlzheimer's disease features early a pathology in the locus coeruleus (LC), yet how sex and life experience shape LC vulnerability remains poorly understood.

methodsWe expressed pseudophosphorylated human tau (htauE14) in LC neurons of TH-Cre rats and exposed both sexes to early- or late-life enrichment or stress. Behavioral, histological, protein, and hippocampal single-nucleus RNA sequencing (snRNA-seq) analyses were performed.

resultsLC-targeted htauE14 impaired learning and increased anxiety-like behavior. Early enrichment reduced htauE14 spread and LC microglia activation, elevated hippocampal brain-derived neurotrophic factor (BDNF), and improved olfactory learning in males. Late enrichment alleviated anxiety and enhanced spatial memory, whereas late stress exacerbated LC degeneration. Hippocampal snRNA-seq revealed sex- and cell type-specific transcriptional responses, with htauE14 preferentially engaging metabolic and synaptic pathways in females, effects amplified by early stress but stabilized by early enrichment. Late-life experiences primarily recruited homeostatic regulatory programs. DISCUSSION: Sex and developmental history critically shape early LC tau-related vulnerability.

Indexed as

Alzheimer DiseaseLocus CoeruleusTauopathiestau ProteinsAnimalsFemaleHippocampusHumansMaleNeuronsRatsRats, TransgenicSex CharacteristicsStress, Psychologicaltau ProteinsBDNFenrichmenthippocampuslocus coeruleuspretangle tausexstresstranscriptomic

Identifiers

PMID41804725
PMCPMC12973150

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.