Disentangling the biological pathways involved in early features of Alzheimer's disease in the Rotterdam Study

Alzheimer's & Dementia : the Journal of the Alzheimer's Association
Shahzad AhmadCornelia M van Duijn

Abstract

Exploring the role of Alzheimer's disease (AD) implicated pathways in the predementia phase may provide new insight for preventive and clinical trials targeting disease specific pathways. We constructed weighted Genetic risk scores, first based on 20 genome-wide significant AD risk variants and second clustering these variants within pathways. Risk scores were investigated for their association with AD, mild cognitive impairment, and brain magnetic resonance imaging phenotypes including white matter lesions, hippocampal volume, and brain volume. The risk score capturing endocytosis pathway was significantly associated with mild cognitive impairment (P = 1.44 × 10-4). Immune response (P = .016) and clathrin/AP2 adaptor complex pathway (P = 3.55 × 10-3) excluding apolipoprotein E also showed modest association with white matter lesions but did not sustain Bonferroni correction (P = 9.09 × 10-4). Our study suggests that the clinical spectrum of early AD pathology is explained by different biological pathways, in particular, the endocytosis, clathrin/AP2 adaptor complex, and immune response pathways, that are independent of apolipoprotein E (APOE).

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Citations

Mar 13, 2019·CNS Neuroscience & Therapeutics·Chang-Juan WeiXiao-Feng Ma
Jul 25, 2019·Human Molecular Genetics·John Hardy, Valentina Escott-Price
Dec 7, 2018·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Xiaoling ZhangLindsay A Farrer
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Apr 18, 2020·Aging Clinical and Experimental Research·Yunyun ZhangZhiming Yu
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Nov 21, 2020·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Lana FaniM Arfan Ikram
Nov 24, 2020·Neurobiology of Aging·Amy N MurrayThomas M Lancaster

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