Aß and tau prions feature in the neuropathogenesis of Down syndrome.
Proc Natl Acad Sci U S A
; 119(46): e2212954119, 2022 11 16.
Article
em En
| MEDLINE
| ID: mdl-36343257
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 Aß and intracellular neurofibrillary tangles composed of tau. Since AD is a double-prion disorder, we asked if both Aß 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 Aß 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 Aß and tau prions. In a cross-sectional analysis of DS donor age at death, we found that the levels of Aß and tau prions increased with age. In contrast to DS brains, the levels of Aß 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Príons
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Síndrome de Down
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Doença de Alzheimer
Tipo de estudo:
Observational_studies
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Prevalence_studies
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Risk_factors_studies
Limite:
Adult
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Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2022
Tipo de documento:
Article