Evidence map›Paper›PMID 42223825›Full record

ArticleMolecular neurobiology2026

Single-Nucleus Profiling Reveals a BBB Senescence Unit Driving AD Pathology in Human Brain.

Yuanwei Zhang, Zhongman Jin, Ruizhen Rao, Linqiao Si, Zhiruo Zhang, Ruixia Ma, Yi Min, Junpu Mei, Zhen Yue, Xiaodong Fang and 1 more

Abstract read
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In one paragraph

Article in Molecular neurobiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

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0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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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.

Yuanwei Zhang *College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
Zhongman Jin *State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China.
Ruizhen RaoIDigital Biotechnology, Sanya, 572025, China.
Linqiao SiIDigital Biotechnology, Sanya, 572025, China.
Zhiruo ZhangIDigital Biotechnology, Sanya, 572025, China.
Ruixia MaIDigital Biotechnology, Sanya, 572025, China.
Yi MinSchool of Life and Health Sciences, Collaborative Innovation Center of Life and Health, Hainan Province Key Laboratory of One Health, Hainan University, Haikou, 570228, Hainan, China.
Junpu MeiIDigital Biotechnology, Sanya, 572025, China.
Zhen YueBGI Research, Sanya, 572025, China.
Xiaodong FangDepartment of Human Cell Biology and Genetics, School of Medicine, SUSTech Homeostatic Medicine Institute (SHMI), Southern University of Science and Technology, Shenzhen, 518055, China. fangxd3@sustech.edu.cn.
Hui WeiState Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China. weihuiray@126.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cellular senescence contributes to Alzheimer's disease (AD) and involves the neurovascular unit, but the molecular mechanisms of cellular senescence in AD pathogenesis remain incompletely understood. Here, we integrate single-nucleus RNA sequencing data from 75 human brain samples to identify a coordinated BBB senescence unit of astrocytes, pericytes, microglia and T cells. Molecular profiling shows inflammatory signaling with maladaptive repair responses in senescent cells. Intercellular communication analysis identifies the SPP1-CD44 axis as central to BBB senescence in AD, with up-regulated SPP1 in senescent microglia and increased CD44 receptor levels in senescent astrocytes, creating a self-sustaining inflammatory loop. Network analysis reveals SPP1 as a hub gene consistently correlated with all AD pathological scores. The clinical significance of SPP1 is further validated in cerebrospinal fluid proteomics data from AD patients. These findings demonstrate that cellular senescence is a crucial pathological process in AD and specifically impacts neurovascular unit via the establishment of a BBB senescence unit.

Indexed as

Alzheimer DiseaseBlood-Brain BarrierBrainCell NucleusCellular SenescenceAstrocytesGene Expression ProfilingHumansHyaluronan ReceptorsMicrogliaPericytesSignal TransductionSingle-Cell Gene Expression AnalysisHyaluronan ReceptorsAlzheimer’s diseaseBlood-brain barrierCellular senescenceNeurovascular unitSingle-nucleus transcriptomicsSPP1-CD44 signaling pathway

Identifiers

PMID42223825

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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.