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Introduction: The apolipoprotein E () ε4 allele is associated with high risk for Alzheimer's disease. It is unclear whether individual levels of the circulating apoE4 protein in ε4 carriers confer additional risk. Measuring apoE4 protein levels from dried blood spots (DBS) has the potential to provide information on genetic status as well as circulating levels and to include these measures in large survey settings.
Methods: We developed a multiplex immunoassay to detect apoE4 protein levels in DBS from 15,974 participants, aged 50+ from Wave 6 of the Survey of Health, Ageing and Retirement in Europe (SHARE).
Results: The apoE4 protein signal was presented in two separable distributions. One distribution corresponded to carriers of at least one copy of the ε4 allele. Fieldwork cofounders affected protein levels but did not explain individual differences.
Discussion: Future research should investigate how genotype and apoE4 level interact with lifestyle and other variables to impact cognitive aging.
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http://dx.doi.org/10.1002/dad2.12555 | DOI Listing |
Sci Signal
September 2025
Science Signaling, AAAS, Washington, DC 20005, USA. Email:
ε4 dysregulates systemic immunity, creating vulnerability for neurodegenerative disease.
View Article and Find Full Text PDFAlzheimers Dement
September 2025
Research Service, VA San Diego Healthcare System, San Diego, California, USA.
Introduction: Among individuals who are amyloid biomarker-positive or apolipoprotein E (APOE) ε4 carriers, arterial stiffness reflected by higher pulse wave velocity (PWV) has been associated with lower cognition cross-sectionally. Less is known about longitudinal associations.
Methods: The sample included 152 older adults without dementia.
Proc Natl Acad Sci U S A
September 2025
Department of Neuroscience, The Scripps Research Institute, San Diego, CA 92037.
Microglia regulate neuronal circuit plasticity. Disrupting their homeostatic function has detrimental effects on neuronal circuit health. Neuroinflammation contributes to the onset and progression of neurodegenerative diseases, including Alzheimer's disease (AD), with several microglial activation genes linked to increased risk for these conditions.
View Article and Find Full Text PDFJ Neurochem
September 2025
Division of Neurogeriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Elucidating the earliest biological mechanisms underlying Alzheimer's disease (AD) is critical for advancing early detection strategies. While amyloid-β (Aβ) and tau pathologies have been central to preclinical AD research, the roles of peripheral biological processes in disease initiation remain underexplored. We investigated patterns of F-MK6240 tau positron emission tomography (PET) and peripheral inflammation across stages defined by Aβ burden and neuronal injury in n = 132 (64.
View Article and Find Full Text PDFCNS Neurosci Ther
September 2025
Key Laboratory of Ministry of Education for Neurological Disorders, Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Background: The apolipoprotein E (ApoE) ε4 allele and type 2 diabetes mellitus (T2DM) are independent risk factors for Alzheimer's disease (AD), the most prevalent neurodegenerative disorder in the elderly. The T2DM patients carrying the ApoE ε4 allele exhibit heightened activation of platelet glycogen synthase kinase-3β (GSK-3β), a key downstream kinase in the insulin signaling pathway, along with more severe cognitive deficits. This observation suggests an intrinsic link between ApoE ε4, GSK-3β, and cognitive dysfunction.
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