Skip to main content
eScholarship
Open Access Publications from the University of California

UCSF

UC San Francisco Previously Published Works bannerUCSF

Aβ and tau prion-like activities decline with longevity in the Alzheimer's disease human brain.

  • Author(s): Aoyagi, Atsushi
  • Condello, Carlo
  • Stöhr, Jan
  • Yue, Weizhou
  • Rivera, Brianna M
  • Lee, Joanne C
  • Woerman, Amanda L
  • Halliday, Glenda
  • van Duinen, Sjoerd
  • Ingelsson, Martin
  • Lannfelt, Lars
  • Graff, Caroline
  • Bird, Thomas D
  • Keene, C Dirk
  • Seeley, William W
  • DeGrado, William F
  • Prusiner, Stanley B
  • et al.

Published Web Location

https://stm.sciencemag.org/content/11/490/eaat8462
No data is associated with this publication.
Abstract

The hallmarks of Alzheimer's disease (AD) are the accumulation of Aβ plaques and neurofibrillary tangles composed of hyperphosphorylated tau. We developed sensitive cellular assays using human embryonic kidney-293T cells to quantify intracellular self-propagating conformers of Aβ in brain samples from patients with AD or other neurodegenerative diseases. Postmortem brain tissue from patients with AD had measurable amounts of pathological Aβ conformers. Individuals over 80 years of age had the lowest amounts of prion-like Aβ and phosphorylated tau. Unexpectedly, the longevity-dependent decrease in self-propagating tau conformers occurred in spite of increasing amounts of total insoluble tau. When corrected for the abundance of insoluble tau, the ability of postmortem AD brain homogenates to induce misfolded tau in the cellular assays showed an exponential decrease with longevity, with a half-life of about one decade over the age range of 37 to 99 years. Thus, our findings demonstrate an inverse correlation between longevity in patients with AD and the abundance of pathological tau conformers. Our cellular assays can be applied to patient selection for clinical studies and the development of new drugs and diagnostics for AD.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Item not freely available? Link broken?
Report a problem accessing this item