Effects of Alzheimer's Disease-Associated Risk Loci on Amyloid-beta Accumulation in the Brain of Idiopathic Normal Pressure Hydrocephalus Patients

摘要

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a dementing condition featuring characteristic symptoms, ventriculomegaly, and normal or slightly elevated cerebrospinal fluid pressure. In Alzheimer's disease (AD) patients, diffuse aggregates of amyloid-beta (A beta) and neurofibrillary hyperphosphorylated tau are detected in the neocortex of the brain, while similar accumulation of A beta is also detected in iNPH. Recent genome-wide association studies have identified several novel risk loci for AD, potentially affecting A beta-related cellular processes. Apart from the apolipoprotein E epsilon 4 allele (APOE4), the risk effect of single loci is low, emphasizing the importance of the polygenic risk score approach when assessing the combined effects.