The role of variation at AβPP, PSEN1, PSEN2, and MAPT in late onset Alzheimer's disease.

Rare mutations in AβPP, PSEN1, and PSEN2 cause uncommon early onset forms of Alzheimer's disease (AD), and common variants in MAPT are associated with risk of other neurodegenerative disorders. We sought to establish whether common genetic variation in these genes confer risk to the common form of AD which occurs later in life (>65 years). We therefore tested single-nucleotide polymorphisms at these loci for association with late-onset AD (LOAD) in a large case-control sample consisting of 3,940 cases and 13,373 controls.

No evidence that extended tracts of homozygosity are associated with Alzheimer's disease.

We sought to investigate the contribution of extended runs of homozygosity in a genome-wide association dataset of 1,955 Alzheimer's disease cases and 955 elderly screened controls genotyped for 529,205 autosomal single nucleotide polymorphisms. Tracts of homozygosity may mark regions inherited from a common ancestor and could reflect disease loci if observed more frequently in cases than controls. We found no excess of homozygous tracts in Alzheimer's disease cases compared to controls and no individual run of homozygosity showed association to Alzheimer's disease.

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10(-5). We tested these variants for association in an independent sample (stage 2).

Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease.

We undertook a two-stage genome-wide association study (GWAS) of Alzheimer's disease (AD) involving over 16,000 individuals, the most powerful AD GWAS to date. In stage 1 (3,941 cases and 7,848 controls), we replicated the established association with the apolipoprotein E (APOE) locus (most significant SNP, rs2075650, P = 1.8 x 10(-157)) and observed genome-wide significant association with SNPs at two loci not previously associated with the disease: at the CLU (also known as APOJ) gene (rs11136000, P = 1.

Education, occupation and retirement age effects on the age of onset of Alzheimer's disease.

Objective: To determine the effects of early life education, mid life employment and later life retirement age on the age of onset (AOO) of Alzheimer's disease (AD).

Methods: Multiple regression analyses were carried out using data for 1320 probable AD cases, of which 382 were males with employment and retirement age data, using informant based information on education and employment.

Results: No relation was found between years of education, best qualification obtained, or employment variables in males and the AOO of AD.

A genome-wide association study for late-onset Alzheimer's disease using DNA pooling.

Background: Late-onset Alzheimer's disease (LOAD) is an age related neurodegenerative disease with a high prevalence that places major demands on healthcare resources in societies with increasingly aged populations. The only extensively replicable genetic risk factor for LOAD is the apolipoprotein E gene. In order to identify additional genetic risk loci we have conducted a genome-wide association (GWA) study in a large LOAD case - control sample, reducing costs through the use of DNA pooling.

Four components describe behavioral symptoms in 1,120 individuals with late-onset Alzheimer's disease.

Objectives: To investigate behavioral components of Alzheimer's disease (AD) and to analyze behavioral components in relation to disease severity, apolipoprotein E genotype (APOE), sex, years of education, age at onset, and cognitive impairment.

Design: Cross-sectional study.

Setting: Data were collected from community-dwelling individuals and those residing in nursing homes.