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Serial propagation of distinct strains of A? prions from Alzheimer's disease patients.

ABSTRACT: An increasing number of studies argues that self-propagating protein conformations (i.e., prions) feature in the pathogenesis of several common neurodegenerative diseases. Mounting evidence contends that aggregates of the amyloid-? (A?) peptide become self-propagating in Alzheimer's disease (AD) patients. An important characteristic of prions is their ability to replicate distinct strains, the biological information for which is enciphered within different conformations of protein aggregates. To investigate whether distinct strains of A? prions can be discerned in AD patients, we performed transmission studies in susceptible transgenic mice using brain homogenates from sporadic or heritable (Arctic and Swedish) AD cases. Mice inoculated with the Arctic AD sample exhibited a pathology that could be distinguished from mice inoculated with the Swedish or sporadic AD samples, which was judged by differential accumulation of A? isoforms and the morphology of cerebrovascular A? deposition. Unlike Swedish AD- or sporadic AD-inoculated animals, Arctic AD-inoculated mice, like Arctic AD patients, displayed a prominent A?38-containing cerebral amyloid angiopathy. The divergent transmission behavior of the Arctic AD sample compared with the Swedish and sporadic AD samples was maintained during second passage in mice, showing that A? strains are serially transmissible. We conclude that at least two distinct strains of A? prions can be discerned in the brains of AD patients and that strain fidelity was preserved on serial passage in mice. Our results provide a potential explanation for the clinical and pathological heterogeneity observed in AD patients.

SUBMITTER: Watts JC

PROVIDER: S-EPMC4104857 | biostudies-other | 2014 Jul

REPOSITORIES: biostudies-other

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Serial propagation of distinct strains of Aβ prions from Alzheimer's disease patients.

Watts Joel C JC Condello Carlo C Stöhr Jan J Oehler Abby A Lee Joanne J DeArmond Stephen J SJ Lannfelt Lars L Ingelsson Martin M Giles Kurt K Prusiner Stanley B SB

Proceedings of the National Academy of Sciences of the United States of America 20140630 28

An increasing number of studies argues that self-propagating protein conformations (i.e., prions) feature in the pathogenesis of several common neurodegenerative diseases. Mounting evidence contends that aggregates of the amyloid-β (Aβ) peptide become self-propagating in Alzheimer's disease (AD) patients. An important characteristic of prions is their ability to replicate distinct strains, the biological information for which is enciphered within different conformations of protein aggregates. To ...[more]

PMID: 24982139

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Dataset Information

Serial propagation of distinct strains of A? prions from Alzheimer's disease patients.

Publications

Serial propagation of distinct strains of Aβ prions from Alzheimer's disease patients.

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