APOE and A beta PP Gene Variation in Cortical and Cerebrovascular Amyloid-beta Pathology and Alzheimer's Disease: A Population-Based Analysis

作者：Peuralinna Terhi; Tanskanen Maarit; Makela Mira; Polvikoski Tuomo; Paetau Anders; Kalimo Hannu; Sulkava Raimo; Hardy John; Lai Shiao Lin; Arepalli Sampath; Hernandez Dena; Traynor Bryan J; Singleton Andrew; Tienari Pentti J; Myllykangas Liisa^*

来源：Journal of Alzheimer's Disease, 2011, 26(2): 377-385.

DOI：10.3233/JAD-2011-102049

• Alzheimer's disease
• amyloid-beta deposition
• A beta PP
• APOE
• cerebral amyloid angiopathy
• neuropathology

Cortical and cerebrovascular amyloid-beta (A beta) deposition is a hallmark of Alzheimer's disease (AD), but also occurs in elderly people not affected by dementia. The apolipoprotein E (APOE) epsilon 4 is a major genetic modulator of A beta deposition and AD risk. Variants of the amyloid-beta protein precursor (A beta PP) gene have been reported to contribute to AD and cerebral amyloid angiopathy (CAA). We analyzed the role of APOE and A beta PP variants in cortical and cerebrovascular A beta deposition, and neuropathologically verified AD (based on modified NIA-RI criteria) in a population-based autopsy sample of Finns aged >= 85 years (Vantaa85 + Study; n = 282). Our updated analysis of APOE showed strong associations of the epsilon 4 allele with cortical (p = 4.91x10(-17)) and cerebrovascular (p = 9.87x10(-11)) A beta deposition as well as with NIA-RI AD (p = 1.62x10(-8)). We also analyzed 60 single nucleotide polymorphisms (SNPs) at the A beta PP locus. In single SNP or haplotype analyses there were no statistically significant A beta PP locus associations with cortical or cerebrovascular A beta deposition or with NIA-RI AD. We sequenced the promoter of the A beta PP gene in 40 subjects with very high A beta deposition, but none of these subjects had any of the previously reported or novel AD-associated mutations. These results suggest that cortical and cerebrovascular A beta depositions are useful quantitative traits for genetic studies, as highlighted by the strong associations with the APOE epsilon 4 variant. Promoter mutations or common allelic variation in the A beta PP gene do not have a major contribution to cortical or cerebrovascular A beta deposition, or very late-onset AD in this Finnish population based study.

• 出版日期2011