uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
A beta and tau prion-like activities decline with longevity in the Alzheimer's disease human brain
Univ Calif San Francisco, UCSF Weill Inst Neurosci, Inst Neurodegenerat Dis, San Francisco, CA 94158 USA;Daiichi Sankyo Co Ltd, Tokyo 1408710, Japan.
Univ Calif San Francisco, UCSF Weill Inst Neurosci, Inst Neurodegenerat Dis, San Francisco, CA 94158 USA;Univ Calif San Francisco, UCSF Weill Inst Neurosci, Dept Neurol, San Francisco, CA 94158 USA.
Univ Calif San Francisco, UCSF Weill Inst Neurosci, Inst Neurodegenerat Dis, San Francisco, CA 94158 USA;Univ Calif San Francisco, UCSF Weill Inst Neurosci, Dept Neurol, San Francisco, CA 94158 USA;AC Immune SA, EPFL Innovat Pk,Bldg B, CH-1015 Lausanne, Switzerland.
Univ Calif San Francisco, UCSF Weill Inst Neurosci, Inst Neurodegenerat Dis, San Francisco, CA 94158 USA.ORCID iD: 0000-0003-4205-0754
Show others and affiliations
2019 (English)In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 11, no 490, article id eaat8462Article in journal (Refereed) Published
Abstract [en]

The hallmarks of Alzheimer's disease (AD) are the accumulation of A beta plaques and neurofibrillary tangles composed of hyperphosphorylated tau. We developed sensitive cellular assays using human embryonic kidney-293T cells to quantify intracellular self-propagating conformers of A beta in brain samples from patients with AD or other neurodegenerative diseases. Postmortem brain tissue from patients with AD had measurable amounts of pathological A beta conformers. Individuals over 80 years of age had the lowest amounts of prion-like A beta and phosphorylated tau. Unexpectedly, the longevity-dependent decrease in self-propagating tau conformers occurred in spite of increasing amounts of total insoluble tau. When corrected for the abundance of insoluble tau, the ability of postmortem AD brain homogenates to induce misfolded tau in the cellular assays showed an exponential decrease with longevity, with a half-life of about one decade over the age range of 37 to 99 years. Thus, our findings demonstrate an inverse correlation between longevity in patients with AD and the abundance of pathological tau conformers. Our cellular assays can be applied to patient selection for clinical studies and the development of new drugs and diagnostics for AD.

Place, publisher, year, edition, pages
AMER ASSOC ADVANCEMENT SCIENCE , 2019. Vol. 11, no 490, article id eaat8462
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-383844DOI: 10.1126/scitranslmed.aat8462ISI: 000466449900004PubMedID: 31043574OAI: oai:DiVA.org:uu-383844DiVA, id: diva2:1318019
Funder
Knut and Alice Wallenberg FoundationStockholm County CouncilAvailable from: 2019-05-24 Created: 2019-05-24 Last updated: 2019-05-24Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records BETA

Ingelsson, MartinLannfelt, Lars

Search in DiVA

By author/editor
Yue, WeizhouIngelsson, MartinLannfelt, Lars
By organisation
Geriatrics
In the same journal
Science Translational Medicine
Neurosciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 248 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf