Relationship between genetic risk factors and markers for Alzheimer's disease pathology.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neuritic plaques (main constituent: β-amyloid [Aβ]) and neurofibrillary tangles (hyperphosphorylated tau protein) in the brain. Abnormalities in Aβ and tau can be measured upon neuropathological examination, in cerebrospinal fluid or by PET. Etiologically, a growing body of evidence suggests that susceptibility to AD is genetically controlled. However, the precise nature of the underlying risk genes and their relation to AD biomarkers remains largely elusive. To this end, we performed a qualitative review of 17 studies (covering 47 polymorphisms in 26 genes) and investigated the potential relation between the most compelling AD risk genes and markers for Aβ and tau in cerebrospinal fluid, PET imaging and neuropathological examination. Of all covered genes, only APOE and PICALM showed consistent effects on Aβ but not on tau, while no obvious effects were observed for CLU, CR1, ACE, SORL and MAPT.
School for Mental Health & Neuroscience, Alzheimer Centrum Limburg, Department of Psychiatry & Neuropsychology, Maastricht University, Maastricht, The Netherlands. lyzel.elias@maastrichtuniversity.nl
Lyzel S
LS
Elias-Sonnenschein
Lars
L
Bertram
Pieter Jelle
PJ
Visser
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D051152:Clusterin / Q000235:genetics / Q000378:metabolism; D055106:Genome-Wide Association Study; D006801:Humans; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D017463:Receptors, Complement 3b / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D001057:Apolipoproteins E; C101410:BIN1 protein, human; C495242:CLU protein, human; C509991:CR1 protein, human; D051152:Clusterin; D034041:Monomeric Clathrin Assembly Proteins; D009687:Nuclear Proteins; C439003:PICALM protein, human; D017463:Receptors, Complement 3b; D025521:Tumor Suppressor Proteins