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

Abstract

Although amyloid plaques composed of fibrillar amyloid-β (Aβ) 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 Aβ fibrils from brain tissue of nondemented elderly individuals with high amyloid loads differ from structures of Aβ fibrils from AD tissue. Two-dimensional solid-state NMR spectra of isotopically labeled Aβ 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-β (Aβ42) fibrils than for 40-residue amyloid-β (Aβ40) 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.

• Authors: Ujjayini Ghosh, Wai-Ming Yau, John Collinge, Robert Tycko
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 118 Issue 45 (11 09 2021) ISSN: 1091-6490 [Electronic] United States
• PMID: 34725161 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides

Topics

• Aged, 80 and over
• Alzheimer Disease (pathology)
• Amyloid beta-Peptides (chemistry)
• Case-Control Studies
• Female
• Frontal Lobe (pathology)
• Humans
• Magnetic Resonance Spectroscopy
• Male
• Plaque, Amyloid (chemistry, pathology)