Patterns and severity of vascular amyloid in Alzheimer ’s disease associated with duplications and missense mutations in APP gene, Down syndrome and sporadic Alzheimer’s disease

In this study, we have compared the severity of amyloid plaque formation and cerebral amyloid angiopathy (CAA), and the subtype pattern of CAA pathology itself, betweenAPP genetic causes of AD (APPdup,APP mutations), older individuals with Down syndrome (DS) showing the pathology of Alzheimer ’s disease (AD) and individuals with sporadic (early and late onset) AD (sEOAD and sLOAD, respectively). The aim of this was to elucidate important group differences and to provide mechanistic insights related to clinical and neuropathological phenotypes. Since lipid and cholesterol metabolism is implicated in AD as well as vascular disease, we additionally aimed to explore the role ofAPOE genotype in CAA severity and subtypes. Plaque formation was greater in DS and missenseAPP mutations than inAPPdup, sEOAD and sLOAD cases. Conversely, CAA was more severe inAPPdup and missenseAPP mutations, and in DS, compared to sEOAD and sLOAD. When stratified by CAA subtype from 1 to 4, there were no differences in plaque scores between the groups, though in patients withAPPdup,APP mutations and sEOAD, types 2 and 3 CAA were more common than type 1. Conversely, in DS, sLOAD and controls, type 1 CAA was more common than types 2 and 3.APOEε4 allele frequency was greater in sEOAD and sLOAD compared toAPPdup, missenseAPP mutations, DS and controls, and varied between each of the CAA phenotypes withAPOEε4 homozygosity being more commonly associated with type 3 CAA than types 1 and 2 CAA in sLOAD and s...
Source: Acta Neuropathologica - Category: Neurology Source Type: research