Oligomeric Aβ in Alzheimer's Disease: Relationship to Plaque and Tangle Pathology, APOE Genotype and Cerebral Amyloid Angiopathy


Zoë van Helmond, MSc, Dementia Research Group, John James Laboratories, Frenchay Hospital, Bristol BS16 1LE, UK (E-mail: zoe.vanhelmond@bristol.ac.uk)


Despite accumulating evidence of a central role for oligomeric amyloid β (Aβ) in the pathogenesis of Alzheimer's Disease (AD), there is scant information on the relationship between the levels and distribution of oligomeric Aβ and those of other neurodegenerative abnormalities in AD. In the present study, we have found oligomeric Aβ to be associated with both diffuse and neuritic plaques (mostly co-localized with Aβ1–42) and with cerebrovascular deposits of Aβ in paraffin sections of formalin-fixed human brain tissue. The amount of oligomeric Aβ that was labeled in the sections correlated with total Aβ plaque load, but not phospho-tau load, cerebral amyloid angiopathy (CAA) severity or APOE genotype. Although soluble, oligomeric and insoluble Aβ 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 Aβ, oligomeric Aβ42, oligomeric Aβ40 and insoluble Aβ did not vary significantly with age. Oligomeric Aβ1–42 and insoluble Aβ levels were significantly higher in women. Overall, the level of insoluble Aβ, but neither oligomeric nor soluble Aβ, was associated with Braak stage, CAA severity and APOEε4 frequency, raising questions as to the role of soluble and oligomeric Aβ in the progression of AD.