Oligomeric Abeta in Alzheimer's disease: relationship to plaque and tangle pathology, APOE genotype and cerebral amyloid angiopathy.
Despite accumulating evidence of a central role for oligomeric amyloid beta (Abeta) in the pathogenesis of Alzheimer's Disease (AD), there is scant information on the relationship between the levels and distribution of oligomeric Abeta and those of other neurodegenerative abnormalities in AD. In the present study, we have found oligomeric Abeta to be associated with both diffuse and neuritic plaques (mostly co-localized with Abeta(1-42)) and with cerebrovascular deposits of Abeta in paraffin sections of formalin-fixed human brain tissue. The amount of oligomeric Abeta that was labeled in the sections correlated with total Abeta plaque load, but not phospho-tau load, cerebral amyloid angiopathy (CAA) severity or APOE genotype. Although soluble, oligomeric and insoluble Abeta levels were all significantly increased in AD brain homogenates, case-to-case variation and overlap between AD and controls were considerable. Over the age-range studied (43-98 years), the levels of soluble Abeta, oligomeric Abeta(42), oligomeric Abeta(40) and insoluble Abeta did not vary significantly with age. Oligomeric Abeta(1-42) and insoluble Abeta levels were significantly higher in women. Overall, the level of insoluble Abeta, but neither oligomeric nor soluble Abeta, was associated with Braak stage, CAA severity and APOEepsilon4 frequency, raising questions as to the role of soluble and oligomeric Abeta in the progression of AD.
van Helmond
Zoë
Z
Dementia Research Group, Institute of Clinical Neurosciences, Clinical Science at North Bristol, University of Bristol, Bristol, UK. zoe.vanhelmond@bristol.ac.uk
Miners
James S
JS
Kehoe
Patrick G
PG
Love
Seth
S
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D016657:Cerebral Amyloid Angiopathy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D012737:Sex Factors; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; C054369:MAPT protein, human; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins