Aβ and tau prions feature in the neuropathogenesis of Down syndrome
| Autor: | Carlo Condello, Alison M. Maxwell, Erika Castillo, Atsushi Aoyagi, Caroline Graff, Martin Ingelsson, Lars Lannfelt, Thomas D. Bird, C. Dirk Keene, William W. Seeley, Daniel P. Perl, Elizabeth Head, Stanley B. Prusiner |
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| Rok vydání: | 2022 |
| Předmět: |
Adult
Aging Prions Down syndrome Intellectual and Developmental Disabilities (IDD) tau Proteins Neurodegenerative A beta Alzheimer's Disease Congenital Rare Diseases Alzheimer Disease Acquired Cognitive Impairment 2.1 Biological and endogenous factors Humans cellular bioassays tau Aetiology Aβ Multidisciplinary Amyloid beta-Peptides Neurosciences Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) Brain Brain Disorders Cross-Sectional Studies Neurological Flavin-Adenine Dinucleotide Dementia Down Syndrome |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America, vol 119, iss 46 |
| ISSN: | 1091-6490 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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