The impact of PICALM genetic variations on reserve capacity of posterior cingulate in AD continuum.
Phosphatidylinositolbinding clathrin assembly protein (PICALM) gene is one novel genetic player associated with late-onset Alzheimer's disease (LOAD), based on recent genome wide association studies (GWAS). However, how it affects AD occurrence is still unknown. Brain reserve hypothesis highlights the tolerant capacities of brain as a passive means to fight against neurodegenerations. Here, we took the baseline volume and/or thickness of LOAD-associated brain regions as proxies of brain reserve capacities and investigated whether PICALM genetic variations can influence the baseline reserve capacities and the longitudinal atrophy rate of these specific regions using data from Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. In mixed population, we found that brain region significantly affected by PICALM genetic variations was majorly restricted to posterior cingulate. In sub-population analysis, we found that one PICALM variation (C allele of rs642949) was associated with larger baseline thickness of posterior cingulate in health. We found seven variations in health and two variations (rs543293 and rs592297) in individuals with mild cognitive impairment were associated with slower atrophy rate of posterior cingulate. Our study provided preliminary evidences supporting that PICALM variations render protections by facilitating reserve capacities of posterior cingulate in non-demented elderly.
Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
Wei
W
Xu
Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China.
Hui-Fu
HF
Wang
College of Medicine and Pharmaceutics, Ocean University of China, China.
Lin
L
Tan
Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
Meng-Shan
MS
Tan
Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
Chen-Chen
CC
Tan
Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China.
Xi-Chen
XC
Zhu
Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
Dan
D
Miao
Department of Radiology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
Wan-Jiang
WJ
Yu
Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Teng
T
Jiang
Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.|Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China.|College of Medicine and Pharmaceutics, Ocean University of China, China.
Lan
L
Tan
Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
Jin-Tai
JT
Yu
D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D058245:Cognitive Reserve; D018450:Disease Progression; D014644:Genetic Variation; D006179:Gyrus Cinguli / Q000502:physiology*; D006801:Humans; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics*
D034041:Monomeric Clathrin Assembly Proteins; C439003:PICALM protein, human