Authors
Shao Wang, Shengzhen Zou, Alzheimer's Disease Neuroimaging Initiative
Published in
Journal of Alzheimer's disease : JAD. Pages 13872877261477047. Aug 14, 2026. Epub Aug 14, 2026.
Abstract
BackgroundAlthough both apolipoprotein E (APOE) ε4 and glial cell line-derived neurotrophic factor (GDNF) are implicated in the pathogenesis of Alzheimer's disease (AD), it remains unclear whether they interact to affect cognitive decline among older adults without dementia.ObjectiveThis study aimed to examine the interactive effects of APOE ε4 and GDNF on longitudinal cognitive decline.MethodsA total of 543 individuals (mean age 73 [±7] years; 43% female) with cognitively unimpaired (CU) or mild cognitive impairment (MCI) were included from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Linear mixed-effects models were used to examine the contributions of cerebrospinal fluid (CSF) GDNF levels and APOE ε4 status to longitudinal changes in cognitive measures, including the Mini-Mental State Examination (MMSE), the Clinical Dementia Rating - Sum of Boxes (CDR-SB), the 13-item Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog-13), and the Rey Auditory Verbal Learning Test (RAVLT) total score.ResultsWe found that the 3-way interaction (APOE ε4 × GDNF × time) was significant for MMSE, CDR-SB, and ADAS-Cog-13, and of marginal significance for RAVLT total score, after adjusting for age, sex, and education. Specifically, individuals who were APOE ε4 carriers with low CSF GDNF levels showed the fastest rate of cognitive decline among the four groups (Low/APOE4-, High/APOE4-, Low/APOE4+, and High/APOE4+).ConclusionsAPOE ε4 appears to interact with CSF GDNF levels to affect longitudinal cognitive decline among older adults without dementia.
PMID:
42599691
Bibliographic data and abstract were imported from PubMed on 15 Aug 2026.
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