Evidence map›Paper›PMID 41996134›Full record

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

Elevated plasma klotho levels attenuate Alzheimer's disease pathologies and cognitive decline in APOE ε4 carriers.

Jie Yang, Jinghua Wang, Wenhui Chai, Laihong Zhang, Anqi Li, Guoyu Lan, Mingxing Jiang, Xiang Fan, Hongjie Yang, Jun Li and 13 more

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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.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

23 authors.

Jie YangDepartment of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Jinghua WangDepartment of Neurology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.
Wenhui ChaiChangji Hui Autonomous Prefecture People's Hospital, Changji, China.
Laihong ZhangInstitute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, China.
Anqi LiInstitute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, China.
Guoyu LanInstitute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, China.
Mingxing JiangInstitute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, China.
Xiang FanDepartment of Medical Imaging, Peking University Shenzhen Hospital, Shenzhen, China.
Hongjie YangDepartment of Nuclear Medicine, Peking University Shenzhen Hospital, Shenzhen, China.
Jun LiDepartment of Nuclear Medicine, Peking University Shenzhen Hospital, Shenzhen, China.
Yalin ZhuInstitute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, China.
Yue CaiInstitute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, China.
Pan SunInstitute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, China.
Zhengbo HeInstitute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, China.
Xin ZhouInstitute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, China.
Zhen LiuInstitute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, China.
Qingyong WangDepartment of Neurology, Shenzhen Guangming District People's Hospital, Shenzhen, China.
Xuhui ChenDepartment of Neurology, Peking University Shenzhen Hospital, Shenzhen, China.
Guanxun ChengDepartment of Medical Imaging, Peking University Shenzhen Hospital, Shenzhen, China.
Lu WangDepartment of Nuclear Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Mengjie DongDepartment of Nuclear Medicine, Peking University Shenzhen Hospital, Shenzhen, China.ORCID 0000-0002-1306-1959
Ying HanDepartment of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.ORCID 0000-0003-0377-7424
Tengfei GuoInstitute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, China.ORCID 0000-0003-2982-0865

Funding

Guangdong Basic and Applied Basic Science Foundation 2023B1515020113Initiative Funding of Hainan University KYQD-ZR-21057Lingang Laboratory ADB510200National Natural Science Foundation of China 82327809National Natural Science Foundation of China 82422027National Natural Science Foundation of China U24A20340Shenzhen Bay Laboratory S241101004Shenzhen Science and Technology Program RCYX20221008092935096STI2030-Major Projects 2022ZD0211800the Sino-German Cooperation M-0759
6 · The paper itself

Abstract

introductionKlotho is a longevity-associated protein with established neuroprotective properties. However, it is unclear how plasma klotho levels relate to Alzheimer's disease (AD) pathologies and cognitive performance.

methodsIn this study, we examined the associations between plasma klotho levels and plasma biomarkers, as well as amyloid beta (Aβ) positron emission tomography (PET), tau PET, neurodegeneration, and cognition, in 354 older adults. Stratified association, interaction, and mediation analyses were conducted to elucidate apolipoprotein E (APOE) ε4-dependent relationships and potential underlying pathways.

resultsHigher plasma klotho levels were associated with lower AD-related biomarkers and cognitive decline in APOE ε4 carriers. Plasma klotho and APOE ε4 exhibited significant or marginal interactions with less abnormal changes in plasma phosphorylated tau217, glial fibrillary acidic protein, neurofilament light chain, Aβ PET, and cognition. These AD-related biomarkers mediated the protective effect of plasma klotho on cognitive function in APOE ε4 carriers. DISCUSSION: This study suggests that plasma klotho is an APOE ε4-dependent protective factor, which may attenuate AD-related pathology and improve cognitive performance.

Indexed as

Alzheimer DiseaseApolipoprotein E4Cognitive DysfunctionGlucuronidaseAgedAged, 80 and overAmyloid beta-PeptidesBiomarkersBrainFemaleHeterozygoteHumansKlotho ProteinsMalePositron-Emission Tomographytau ProteinsAmyloid beta-PeptidesApolipoprotein E4BiomarkersGlucuronidaseKlotho ProteinsKL protein, humantau ProteinsAlzheimer's diseaseapolipoprotein E ε4 carriercognitive declineplasma klotho

Identifiers

PMID41996134
PMCPMC13089206

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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.