Structural differences in amyloid-ß fibrils from brains of nondemented elderly individuals and Alzheimer's disease patients.

ABSTRACT

Although amyloid plaques composed of fibrillar amyloid-ß (Aß) assemblies are a diagnostic hallmark of Alzheimer's disease (AD), quantities of amyloid similar to those in AD patients are observed in brain tissue of some nondemented elderly individuals. The relationship between amyloid deposition and neurodegeneration in AD has, therefore, been unclear. Here, we use solid-state NMR to investigate whether molecular structures of Aß fibrils from brain tissue of nondemented elderly individuals with high amyloid loads differ from structures of Aß fibrils from AD tissue. Two-dimensional solid-state NMR spectra of isotopically labeled Aß fibrils, prepared by seeded growth from frontal lobe tissue extracts, are similar in the two cases but with statistically significant differences in intensity distributions of cross-peak signals. Differences in solid-state NMR data are greater for 42-residue amyloid-ß (Aß42) fibrils than for 40-residue amyloid-ß (Aß40) fibrils. These data suggest that similar sets of fibril polymorphs develop in nondemented elderly individuals and AD patients but with different relative populations on average.