Evidence map›Paper›PMID 41163175›Full record

ArticleMolecular neurodegeneration2025

Interplay between astrocyte reactivity and APOE ε4 status is associated with accelerated pTau-related tau pathology in Alzheimer's disease.

Xiaoxie Mao, Yan Wang, Ying Luan, Ying Wang, Jie Wang, Wenlin Dai, Yihui Guan, Qi Huang, Roger N Gunn, Rik Ossenkoppele and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular neurodegeneration, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. Review
  3. Metabotropic glutamate receptor 5 is associated with plasma GFAP dependent on age.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  4. Review
  5. Impaired glymphatic function is associated with synaptic loss in cognitive impairment.European journal of nuclear medicine and molecular imaging · 2026
    Article
  6. Article
  7. Article
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.

Xiaoxie Mao *Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China.
Yan Wang *Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China.
Ying Luan *Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China.
Ying Wang *Department of Gerontology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China.
Jie WangDepartment of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China.
Wenlin DaiCenter for Applied Statistics, Institute of Statistics and Big Data, Renmin University of China, Beijing, China.
Yihui GuanDepartment of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China.
Qi HuangDepartment of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China.
Roger N GunnDepartment of Brain Sciences, Imperial College London, London, UK.
Rik OssenkoppeleClinical Memory Research Unit, Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden.
Binyin LiDepartment of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. libinyin@126.com.
Zijing LiCenter for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, 361102, China. zijing.li@xmu.edu.cn.
Qihao GuoDepartment of Gerontology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China. qhguo@sjtu.edu.cn.
Fang XieDepartment of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China. Fangxie@fudan.edu.cn.ORCID http://orcid.org/0000-0003-2667-281X
Alzheimer’s Disease Neuroimaging Initiative

Funding

STI2030-Major Projects 2022ZD0213800the National Science Foundation of China 81801752, 82171473, 82201583, and 82071962the startup fund of Huashan Hospital, Fudan University 2017QD081
6 · The paper itself

Abstract

backgroundVarious plasma phosphorylated tau species have been shown to be associated with amyloid-β (Aβ) PET and Tau PET in Alzheimer’s disease (AD), but whether APOE ε4 affects the interaction between glial fibrillary acidic protein (GFAP) and phosphorylated tau (pTau), and whether a three-way interaction exists among APOE ε4, GFAP, and pTau that influences AD progression remain unclear.

methodsThe study included 563 participants from the Chinese Preclinical Alzheimer’s Disease Study (CPAS) and 243 from Alzheimer’s Disease Neuroimaging Initiative (ADNI), all of whom underwent Aβ PET, magnetic resonance imaging (MRI), neuropsychological assessments, and plasma biomarker analyses (GFAP, pTau181, pTau231, pTau217), with subsets undergoing Tau PET. The longitudinal data of 101 participants from ADNI were additionally included. We employed linear regression models with interaction terms to examine how APOE ε4 status and plasma GFAP levels modulate the relationships between plasma pTau biomarkers and AD pathology cross-sectionally and longitudinally.

resultsPlasma GFAP and pTau biomarkers (pTau181, pTau231, pTau217) are significantly elevated in Aβ-positive individuals, with stronger Aβ–pTau associations observed in APOE ε4 carriers (CPAS: β = 0.26, p = 0.003 for pTau231; ADNI: β = 0.45, p < 0.001 for pTau181). Across two cohorts, plasma GFAP levels significantly strengthened the associations between pTau biomarkers and Tau PET. Furthermore, subsequent analyses revealed that this modulatory effect of GFAP on the links between pTau and PET-derived pathological changes was more pronounced in APOE ε4 non-carriers, whereas in APOE ε4 carriers, a significant interaction between GFAP and pTau was only observed in specific Braak stage-specific regions within the CPAS cohort. In longitudinal analyses, we also observed stronger pTau181-associated longitudinal tau accumulation in individuals with high GFAP levels (Braak III-IV).

conclusionWe demonstrate that APOE ε4 status critically modulates the relationship between pTau and Aβ pathology, whereas plasma GFAP primarily influences pTau–tau pathology associations, particularly in individuals without APOE ε4 allele. These findings underscore the role of reactive astrogliosis in tau propagation and support the utility of plasma biomarkers for AD diagnosis and prognosis.

Indexed as

Alzheimer DiseaseApolipoprotein E4Astrocytestau ProteinsAgedAged, 80 and overAmyloid beta-PeptidesBiomarkersCross-Sectional StudiesDisease ProgressionFemaleGlial Fibrillary Acidic ProteinHumansLongitudinal StudiesMalePhosphorylationAmyloid beta-PeptidesApolipoprotein E4BiomarkersGlial Fibrillary Acidic Proteintau ProteinsAlzheimer’s diseaseAPOE ε4Glial fibrillary acidic proteinPhosphorylated tauTau PET

Identifiers

PMID41163175
PMCPMC12573940

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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 OpenQuestion graph.