Serial propagation of distinct strains of Aβ prions from Alzheimer’s disease patients
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...
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ftcdlib:oai:escholarship.org:ark:/13030/qt5hs7p6b1 2023-09-05T13:16:46+02:00 Serial propagation of distinct strains of Aβ prions from Alzheimer’s disease patients Watts, Joel C Condello, Carlo Stöhr, Jan Oehler, Abby Lee, Joanne DeArmond, Stephen J Lannfelt, Lars Ingelsson, Martin Giles, Kurt Prusiner, Stanley B 10323 - 10328 2014-07-15 https://escholarship.org/uc/item/5hs7p6b1 unknown eScholarship, University of California qt5hs7p6b1 https://escholarship.org/uc/item/5hs7p6b1 public Proceedings of the National Academy of Sciences of the United States of America, vol 111, iss 28 Neurodegenerative Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) Dementia Neurosciences Alzheimer's Disease Brain Disorders Aging Acquired Cognitive Impairment Aetiology 2.1 Biological and endogenous factors Neurological Alzheimer Disease Amyloid beta-Peptides Animals Brain Humans Mice Transgenic Prions neurodegeneration bioluminescence imaging seeding proteinopathies article 2014 ftcdlib 2023-08-21T18:05:50Z 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 investigate whether distinct strains of Aβ 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 Aβ isoforms and the morphology of cerebrovascular Aβ deposition. Unlike Swedish AD- or sporadic AD-inoculated animals, Arctic AD-inoculated mice, like Arctic AD patients, displayed a prominent Aβ38-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 Aβ strains are serially transmissible. We conclude that at least two distinct strains of Aβ 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. Article in Journal/Newspaper Arctic University of California: eScholarship Arctic |
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Open Polar |
collection |
University of California: eScholarship |
op_collection_id |
ftcdlib |
language |
unknown |
topic |
Neurodegenerative Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) Dementia Neurosciences Alzheimer's Disease Brain Disorders Aging Acquired Cognitive Impairment Aetiology 2.1 Biological and endogenous factors Neurological Alzheimer Disease Amyloid beta-Peptides Animals Brain Humans Mice Transgenic Prions neurodegeneration bioluminescence imaging seeding proteinopathies |
spellingShingle |
Neurodegenerative Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) Dementia Neurosciences Alzheimer's Disease Brain Disorders Aging Acquired Cognitive Impairment Aetiology 2.1 Biological and endogenous factors Neurological Alzheimer Disease Amyloid beta-Peptides Animals Brain Humans Mice Transgenic Prions neurodegeneration bioluminescence imaging seeding proteinopathies Watts, Joel C Condello, Carlo Stöhr, Jan Oehler, Abby Lee, Joanne DeArmond, Stephen J Lannfelt, Lars Ingelsson, Martin Giles, Kurt Prusiner, Stanley B Serial propagation of distinct strains of Aβ prions from Alzheimer’s disease patients |
topic_facet |
Neurodegenerative Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) Dementia Neurosciences Alzheimer's Disease Brain Disorders Aging Acquired Cognitive Impairment Aetiology 2.1 Biological and endogenous factors Neurological Alzheimer Disease Amyloid beta-Peptides Animals Brain Humans Mice Transgenic Prions neurodegeneration bioluminescence imaging seeding proteinopathies |
description |
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 investigate whether distinct strains of Aβ 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 Aβ isoforms and the morphology of cerebrovascular Aβ deposition. Unlike Swedish AD- or sporadic AD-inoculated animals, Arctic AD-inoculated mice, like Arctic AD patients, displayed a prominent Aβ38-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 Aβ strains are serially transmissible. We conclude that at least two distinct strains of Aβ 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. |
format |
Article in Journal/Newspaper |
author |
Watts, Joel C Condello, Carlo Stöhr, Jan Oehler, Abby Lee, Joanne DeArmond, Stephen J Lannfelt, Lars Ingelsson, Martin Giles, Kurt Prusiner, Stanley B |
author_facet |
Watts, Joel C Condello, Carlo Stöhr, Jan Oehler, Abby Lee, Joanne DeArmond, Stephen J Lannfelt, Lars Ingelsson, Martin Giles, Kurt Prusiner, Stanley B |
author_sort |
Watts, Joel C |
title |
Serial propagation of distinct strains of Aβ prions from Alzheimer’s disease patients |
title_short |
Serial propagation of distinct strains of Aβ prions from Alzheimer’s disease patients |
title_full |
Serial propagation of distinct strains of Aβ prions from Alzheimer’s disease patients |
title_fullStr |
Serial propagation of distinct strains of Aβ prions from Alzheimer’s disease patients |
title_full_unstemmed |
Serial propagation of distinct strains of Aβ prions from Alzheimer’s disease patients |
title_sort |
serial propagation of distinct strains of aβ prions from alzheimer’s disease patients |
publisher |
eScholarship, University of California |
publishDate |
2014 |
url |
https://escholarship.org/uc/item/5hs7p6b1 |
op_coverage |
10323 - 10328 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Proceedings of the National Academy of Sciences of the United States of America, vol 111, iss 28 |
op_relation |
qt5hs7p6b1 https://escholarship.org/uc/item/5hs7p6b1 |
op_rights |
public |
_version_ |
1776198232559321088 |