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Record W4409130990 · doi:10.1371/journal.pone.0320561

Depression as a risk factor for Alzheimer’s disease: A human post-mortem study

2025· article· en· W4409130990 on OpenAlexafffundabout
Mizuki Morisaki, Farnoosh Rezaali, Laurie C. Lau, Delphine Boche, Golam M. Khandaker, Gustavo Turecki, Lindsey I. Sinclair

Bibliographic record

VenuePLoS ONE · 2025
Typearticle
Languageen
FieldNeuroscience
TopicTryptophan and brain disorders
Canadian institutionsMcGill UniversityDouglas Mental Health University InstituteBell (Canada)
FundersElizabeth Blackwell Institute for Health Research, University of BristolAlzheimer's SocietyAlzheimer SocietyWellcome Trust
KeywordsNeuroinflammationDepression (economics)DementiaMedicineAlzheimer's diseaseInterleukin 6Internal medicineDiseasePathologyPsychologyEndocrinologyCytokine

Abstract

fetched live from OpenAlex

Depression is associated with persistent low mood. In mid to late life, it has been identified as a risk factor for Alzheimer's disease (AD) with evidence that depression might be an early manifestation of AD. Although the underlying mechanisms by which depression enhances AD development remain unknown, there are several features commonly seen in both diseases such as the presence of neuroinflammation. In this study, we aimed to identify whether neuroinflammation is increased in depression as observed in the early stages of AD by examining post-mortem human brain tissue. Post-mortem human brain tissue from 54 cases with depression and 37 controls without depression were retrieved from the Douglas Bell Canada Brain Bank. Sixteen early-stage AD cases defined as a Braak stage III-IV and 15 controls were sourced from the South West Dementia Brain Bank. Frozen tissue from the dorsal prefrontal cortex was obtained for all cases in order to measure inflammatory proteins (IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and TNF-α) and endothelial markers (ICAM-1, VCAM) using ELISA and MesoScale Multiplex Assays. In the depression group, increase of IL-6 and IL-10, and decrease of IL-1β were observed compared to controls, with no changes detected for the other cytokines and the endothelial markers. In early-stage AD cases, only increased ICAM-1 expression was found compared to controls, indicating endothelial activation as an early feature of AD. None of the cytokines measured showed alteration of their expression in early-stage AD cases. Depression, but not AD, was associated with evidence of neuroinflammation. Depression may increase AD risk through different mechanism(s) than inflammation.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.083
GPT teacher head0.320
Teacher spread0.237 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations5
Published2025
Admission routes3
Has abstractyes

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Same venuePLoS ONESame topicTryptophan and brain disordersFrench-language works237,207