Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 118, Issue 45, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2111863118
Keywords
amyloid structure; Alzheimer's disease; solid-state NMR
Categories
Funding
- Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH
- UK Medical Research Council
- National Institute of Health Research University College London Hospital/UCL Biomedical Research Centre
- NIH [P30AG010161, R01AG15819]
- Reta Lila Weston Trust for Medical Research
- Progressive Supranuclear Palsy [Europe] Association
- MRC
Ask authors/readers for more resources
This study investigated the molecular structures of Aβ fibrils in brain tissue of nondemented elderly individuals and AD patients using solid-state NMR, revealing that similar sets of fibril polymorphs develop in both groups but with different relative populations on average. The differences in solid-state NMR data were more significant for Aβ42 fibrils compared to Aβ40 fibrils.
Although amyloid plaques composed of fibrillar amyloid-beta (A beta) 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 A beta fibrils from brain tissue of nondemented elderly individuals with high amyloid loads differ from structures of A beta fibrils from AD tissue. Twodimensional solid-state NMR spectra of isotopically labeled A beta 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-beta (A beta 42) fibrils than for 40-residue amyloid-beta (A beta 40) 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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available