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  • Liu, HeCase Western Reserve Univ, OH 44106 USA (författare)

Distinct conformers of amyloid beta accumulate in the neocortex of patients with rapidly progressive Alzheimers disease

  • Artikel/kapitelEngelska2021

Förlag, utgivningsår, omfång ...

  • Elsevier,2021
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:liu-181691
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-181691URI
  • https://doi.org/10.1016/j.jbc.2021.101267DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Funding Agencies|Alberta Innovates Bio Solutions [FP00209618]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1RF1AG061797, AG066512, AG060882]; Swedish Research CouncilSwedish Research CouncilEuropean Commission [2019-04405, 2016-00748]; Swedish Alzheimer Foundation; Swedish Brain Foundation; Torsten Soderberg Foundation
  • Amyloid beta (A beta) deposition in the neocortex is a major hallmark of Alzheimers disease (AD), but the extent of deposition does not readily explain phenotypic diversity and rate of disease progression. The prion strain-like model of disease heterogeneity suggests the existence of different conformers of A beta. We explored this paradigm using conformation-dependent immunoassay (CDI) for A beta and conformation-sensitive luminescent conjugated oligothiophenes (LCOs) in AD cases with variable progression rates. Mapping the A beta conformations in the frontal, occipital, and temporal regions in 20 AD patients with CDI revealed extensive interindividual and anatomical diversity in the structural organization of A beta with the most significant differences in the temporal cortex of rapidly progressive AD. The fluorescence emission spectra collected in situ from A beta plaques in the same regions demonstrated considerable diversity of spectral characteristics of two LCOs-quatroformylthiophene acetic acid and heptaformylthiophene acetic acid. Heptaformylthiophene acetic acid detected a wider range of A beta deposits, and both LCOs revealed distinct spectral attributes of diffuse and cored plaques in the temporal cortex of rapidly and slowly progressive AD and less frequent and discernible differences in the frontal and occipital cortex. These and CDI findings indicate a major conformational diversity of A beta accumulating in the neocortex, with the most notable differences in temporal cortex of cases with shorter disease duration, and implicate distinct A beta conformers (strains) in the rapid progression of AD.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Kim, ChaeCase Western Reserve Univ, OH 44106 USA (författare)
  • Haldiman, TracyCase Western Reserve Univ, OH 44106 USA (författare)
  • Sigurdson, Christina J.Univ Calif San Diego, CA 92093 USA; Univ Calif San Diego, CA 92093 USA (författare)
  • Nyström, SofieLinköpings universitet,Kemi,Tekniska fakulteten(Swepub:liu)sofny42 (författare)
  • Nilsson, PeterLinköpings universitet,Kemi,Tekniska fakulteten(Swepub:liu)petni61 (författare)
  • Cohen, Mark L.Case Western Reserve Univ, OH 44106 USA; Case Western Reserve Univ, OH USA (författare)
  • Wisniewski, ThomasNYU, NY USA; NYU, NY USA (författare)
  • Hammarström, PerLinköpings universitet,Kemi,Tekniska fakulteten(Swepub:liu)perha81 (författare)
  • Safar, Jiri G.Case Western Reserve Univ, OH 44106 USA; Case Western Reserve Univ, OH 44106 USA (författare)
  • Case Western Reserve Univ, OH 44106 USAUniv Calif San Diego, CA 92093 USA; Univ Calif San Diego, CA 92093 USA (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of Biological Chemistry: Elsevier297:50021-92581083-351X

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