A Specific Enzyme-Linked Immunosorbent Assay for Measuring β-Amyloid Protein Oligomers in Human Plasma and Brain Tissue of Patients With Alzheimer Disease

Open Access
Publisher Website
Google Scholar
Abstract
Alzheimer disease (AD) is characterized by the progressive accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles. The protein subunit of the amyloid plaques, β-amyloid (Aβ), does not occur as a single molecular species; many different Aβ-containing peptides have been detected in human cerebrospinal fluid (CSF) and/or brain tissue.1,2 The most common Aβ isoform in vivo is Aβ1-40, ie, a peptide that begins at Asp1 and terminates at Val40 of the Aβ region of amyloid precursor protein (APP). Increased accumulation of Aβ1-42, a peptide that differs from Aβ1-40 by the inclusion of Ile41 and Ala42, is particularly associated with development of AD. The extra 2 hydrophobic amino acids of Aβ42 greatly enhance its aggregation propensity,3 leading to accelerated formation of small (low-n) Aβ oligomers (oAβ), larger intermediate assemblies like protofibrils, and eventually the typical approximately 8-nm amyloid fibrils found abundantly in neuritic plaques and amyloid-bearing microvessels. Small, soluble oligomers of Aβ have been linked to neuronal toxic effects and synaptic failure (for review, see the article by Walsh and Selkoe4). How the oligomeric assemblies reach a balance with monomeric Aβ and large protofibrils and fibrils in the human brain is under investigation.