Quantification of Alzheimer pathology in ageing and dementia:: age-related accumulation of amyloid-β(42) peptide in vascular dementia

Clinicopathological observations suggest there is considerable overlap between vascular dementia (VaD) and Alzheimer's disease (AD). We used immunochemical methods to compare quantities of amyloid-beta (A beta) peptides in post mortem brain samples from VaD, AD subjects and nondemented ageing controls. Total A beta peptides extracted from temporal and frontal cortices were quantified using a previously characterized sensitive homogenous time-resolved fluorescence (HTRF) assay. The HTRF assays and immunocapture mass spectrometric analyses revealed that the A beta(42) species were by far the predominant form of extractable peptide compared with A beta(40) peptide in VaD brains. The strong signal intensity for the peak representing A beta(4-42) peptide confirmed that these N-terminally truncated species are relatively abundant. Absolute quantification by HTRF assay showed that the mean amount of total A beta(42) recovered from VaD samples was approximately 50% of that in AD, and twice that in the age-matched controls. Linear correlation analysis further revealed an increased accumulation with age of both A beta peptides in brains of VaD subjects and controls. Interestingly, VaD patients surviving beyond 80 years of age exhibited comparable A beta(42) concentrations with those in AD in the temporal cortex. Our findings suggest that brain A beta accumulates increasingly with age in VaD subjects more so than in elderly without cerebrovascular disease and support the notion that they acquire Alzheimer-like pathology in older age.