Identification of biomarkers and molecular mechanisms implicated in genetic variations underlying Alzheimer’s disease pathogenesis

Abstract

Identification of biomarkers and molecular mechanisms implicated in genetic variations underlying Alzheimer’s disease pathogenesis Hai Duc Nguyen a,*, Giang Huong Vu b, Woong-Ki Kim c a Division of Microbiology, Tulane National Primate Research Center, Tulane University, Covington, LA, USA b Hong Bang Health Center, Hai Phong, Viet Nam c Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, USA A R T I C L E I N F O Handling Editor: Prof A Angelo Azzi Keywords: GWAS Alzheimer’s disease Biomarkers Molecular mechanisms A B S T R A C T We analyzed data from human genome-wide association studies (GWASs) to identify genetic variants and biological pathways linked to Alzheimer’s disease (AD). Ten AD biomarkers (APOE, NECTIN2, APOC1, APOC1P1, TOMM40, RNU4-67P, KRAS, Y_RNA, THORLNC, LINC01956) were found across studies, including six central genetic variants (MAPT (rs242557-A), GRIN2B (rs74442473-G), APOE (rs438811-T), ANK3 (rs438811-T), BIN1 (rs744373-G), and BDNF (rs7481773-A)). ANK3 (rs438811-T) and GRIN2B (rs74442473-G) were essential hub biomarkers for amyloid plaques, while MAPT (rs242557-A) and BIN1 (rs744373-G) were crucial for neurofibrillary tangles (NFTs). Higher-risk AD biomarkers were associated with increased protein-lipid complex formation, while lower-risk AD biomarkers were correlated with improved synaptic function. Six essential miRNAs (hsa-miR-124–3p, 15a-5p, 16–5p, 204–5p, 520g-3p, 520h) and three transcription factors (ZMAT4, ZBED6, FOXG1) emerged as possible candidates to reveal the genetic differences that lead to amyloid plaques, NFTs, and ultimately AD. These findings serve as a basis for potential AD treatments and offer new avenues for therapeutic approaches to directly target the genetic variations and processes associated with the disease.