Evidence map›Paper›PMID 42594145›Full record

ArticlePloS one2026

Unraveling the molecular Nexus of Alzheimer's Disease and HIV encephalitis: The role of cellular senescence and transcriptional regulation.

Hao Zhang, WenJun Chen, ShuYou Yuan, ShaoXiang Ding, HongXia Bao, Bo Cai, JunKai Sun, Wei Lu, HaoGang Zhu, GuoXun Shi

Abstract read
In one paragraph

Article in PloS one, 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
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0citing papers in PubMed
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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

10 authors.

Hao ZhangGeriatrics Center, Wuxi Second Geriatric Hospital, Wuxi, Jiangsu Province, China.
WenJun ChenNeurology Department, Wuxi Second Geriatric Hospital, Wuxi, Jiangsu Province, China.
ShuYou YuanLaboratory Department, Wuxi Second Geriatric Hospital, Wuxi, Jiangsu Province, China.
ShaoXiang DingGeriatrics Center, Wuxi Second Geriatric Hospital, Wuxi, Jiangsu Province, China.
HongXia BaoGeriatrics Center, Wuxi Second Geriatric Hospital, Wuxi, Jiangsu Province, China.
Bo CaiPathology department, Wuxi Second Geriatric Hospital, Wuxi, Jiangsu Province, China.
JunKai SunDepartment of Interventional Radiology, Wuxi No. 5 People's Hospital, Wuxi, Jiangsu Province, China.
Wei LuGeriatrics Center, Wuxi Second Geriatric Hospital, Wuxi, Jiangsu Province, China.ORCID https://orcid.org/0009-0008-6566-5368
HaoGang ZhuGeriatrics Center, Wuxi Second Geriatric Hospital, Wuxi, Jiangsu Province, China.
GuoXun ShiRheumatology Department, Wuxi Second People's Hospital, Wuxi, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alzheimer's disease (AD) and HIV-associated neurocognitive disorder (HAND) share progressive cognitive decline. Their common molecular mechanisms remain poorly understood. Current therapeutic approaches lack effective biomarkers for early diagnosis and intervention. We integrated transcriptomic profiles from multiple independent cohorts across brain tissues and blood. We systematically evaluated diagnostic performance using machine learning algorithms including Random Forest, Support Vector Machine, and XGBoost. Notably, FOXO3 emerged as the top cross-disease biomarker. FOXO3 achieved diagnostic accuracy in AD temporal cortex (area under the curve [AUC] = 0.922, 95% CI: 0.885-0.959). FOXO3 showed diagnostic performance in HAND frontal cortex (AUC = 0.771, 95% CI: 0.724-0.818). FOXO3 expression positively correlated with APP (R = 0.558). FOXO3 expression negatively correlated with MAPT (R = -0.690) and SORL1 (R = -0.856). ACE showed strong positive correlation with FOXO3 (R = 0.685), suggesting vascular involvement. STAT3 and ZNF341 were identified from 21 transcription factor candidates. STAT3 ranked first in HAND integrated cohort (n = 107, AUC = 0.759). STAT3 may function as an inflammatory mediator through JAK-STAT signaling. ZNF341 showed strongest transcriptional association with disease status (β = 5.09 in AD, β = 4.85 in HAND). The two-gene panel (FOXO3-ZNF341) achieved diagnostic accuracy in blood samples (AUC = 0.764, n = 329). This performance approaches clinical utility thresholds. Blood-based detection offers non-invasive diagnostic potential. Saturation analysis identified three molecules as optimal panel size. Marginal AUC gains declined below 0.02 beyond this threshold. FOXO3, STAT3, and ZNF341 showed stable selection frequency (97%, 65%, and 100%, respectively). PI3K-Akt and FoxO signaling pathways were enriched, which are known to regulate apoptosis and cell survival. Taken together, these computational findings indicate FOXO3 transcriptional regulatory activity in neurodegeneration. The three-molecule panel represents candidate blood-based diagnostic biomarkers. These candidate biomarkers warrant further investigation in independent clinical cohorts.

Indexed as

Alzheimer DiseaseCellular SenescenceBiomarkersFemaleForkhead Box Protein O3Gene Expression ProfilingGene Expression RegulationHumansMaleSTAT3 Transcription FactorTranscription, GeneticBiomarkersForkhead Box Protein O3FOXO3 protein, humanSTAT3 Transcription Factor

Identifiers

PMID42594145
PMCPMC13472368

What Socratic holds

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Registered trials

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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 Socratic graph.