Aβ and tau prions feature in the neuropathogenesis of Down syndrome
Abstract
Down syndrome (DS) is caused by the triplication of chromosome 21 and is the most common chromosomal disorder in humans. Those individuals with DS who live beyond age 40 y develop a progressive dementia that is similar to Alzheimer’s disease (AD). Both DS and AD brains exhibit numerous extracellular amyloid plaques composed of Aβ and intracellular neurofibrillary tangles composed of tau. Since AD is a double-prion disorder, we asked if both Aβ and tau prions feature in DS. Frozen brains from people with DS, familial AD (fAD), sporadic AD (sAD), and age-matched controls were procured from brain biorepositories. We selectively precipitated Aβ and tau prions from DS brain homogenates and measured the number of prions using cellular bioassays. In brain extracts from 28 deceased donors with DS, ranging in age from 19 to 65 y, we found nearly all DS brains had readily measurable levels of Aβ and tau prions. In a cross-sectional analysis of DS donor age at death, we found that the levels of Aβ and tau prions increased with age. In contrast to DS brains, the levels of Aβ and tau prions in the brains of 37 fAD and sAD donors decreased as a function of age at death. Whether DS is an ideal model for assessing the efficacy of putative AD therapeutics remains to be determined.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 07, 2022
- Source ID
- 10.1073/pnas.2212954119
Entities
People
- Alison M. Maxwell
- Atsushi Aoyagi
- Carlo Condello
- Caroline Graff
- Christopher Keene
- Daniel P. Perl
- Elizabeth Head
- Erika Castillo
- Lars Lannfelt
- Martin Ingelsson
- Stanley B. Prusiner
- Thomas D. Bird
- William Seeley
Organizations
- Daiichi Sankyo
- Defense Health Agency
- F. Edward Hébert School of Medicine
- Karolinska Institutet
- Karolinska University Hospital
- National Institute on Aging
- National Institutes of Health
- University Health Network
- University of California
- University of California, San Francisco
- University of Toronto
- University of Washington
- Uppsala University