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

Lookup NU author(s): Natalie Cookson, Arthur Oakley, Dr Margaret Piggott, Dr Christopher Morris, Dr Evelyn Jaros, Emeritus Professor Robert Perry, Professor Rose Anne Kenny, Dr Clive Ballard, Professor Raj KalariaORCiD

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Abstract

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.

Publication metadata

Author(s): Lewis H, Beher D, Cookson N, Oakley A, Piggott M, Morris CM, Jaros E, Perry R, Ince P, Kenny RA, Ballard CG, Shearman MS, Kalaria RN

Publication type: Article

Publication status: Published

Journal: Neuropathology and Applied Neurobiology

Year: 2006

Volume: 32

Issue: 2

Pages: 103-118

ISSN (print): 0305-1846

ISSN (electronic): 1365-2990

Publisher: Wiley-Blackwell Publishing Ltd.

URL: http://dx.doi.org/10.1111/j.1365-2990.2006.00696.x

DOI: 10.1111/j.1365-2990.2006.00696.x

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