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

• Published in: Neuropathology and applied neurobiology Vol. 32; no. 2; pp. 103 - 118
• Main Authors: Lewis, H., Beher, D., Cookson, N., Oakley, A., Piggott, M., Morris, C. M., Jaros, E., Perry, R., Ince, P., Kenny, R. A., Ballard, C. G., Shearman, M. S., Kalaria, R. N.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2006; Blackwell Science
• Subjects: Aged; Aged, 80 and over; Aging; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; amyloid-β peptide; Apolipoproteins E - genetics; Biological and medical sciences; Brain - pathology; brain ageing; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; dementia; Dementia, Vascular - genetics; Dementia, Vascular - pathology; Female; Genotype; Human viral diseases; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Infectious diseases; Male; Medical sciences; Middle Aged; Neurology; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; vascular dementia; Viral diseases; Viral diseases of the nervous system; Nervous system diseases; Senescence; Vascular dementia; Peptides; Alzheimer disease; brain ageing; Ageing; amyloid-β peptide; Cerebral disorder; Anatomic pathology; β Amyloid protein; Central nervous system disease; dementia; Degenerative disease; Alzheimer's disease; Age
• ISSN: 0305-1846; 1365-2990
• DOI: 10.1111/j.1365-2990.2006.00696.x

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‐β (Aβ) peptides in post mortem brain samples from VaD, AD subjects and nondemented ageing controls. Total Aβ 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 Aβ(42) species were by far the predominant form of extractable peptide compared with Aβ(40) peptide in VaD brains. The strong signal intensity for the peak representing Aβ(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 Aβ(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 Aβ peptides in brains of VaD subjects and controls. Interestingly, VaD patients surviving beyond 80 years of age exhibited comparable Aβ(42) concentrations with those in AD in the temporal cortex. Our findings suggest that brain Aβ 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.