Toggle Main Menu Toggle Search

Open Access padlockePrints

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 Kalaria

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


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


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share