Expression of an alternatively spliced variant of SORL1 in neuronal dendrites is decreased in patients with Alzheimer's disease

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DOI

  • Giulia Monti
  • Mads Kjolby
  • Anne Mette G Jensen
  • Mariet Allen, Mayo Clinic
  • ,
  • Juliane Reiche, Institute of General Practice and Family Medicine, Jena University Hospital, University of Jena, Jena, Germany.
  • ,
  • Peter L Møller
  • Raquel Comaposada-Baró, Aarhus Universitet
  • ,
  • Bartlomiej E Zolkowski, Aarhus Universitet
  • ,
  • Cármen Vieira
  • ,
  • Margarita Melnikova Jørgensen
  • Ida E Holm
  • ,
  • Paul N Valdmanis, Univ Washington, University of Washington, University of Washington Seattle, University of Washington Tacoma, Dept Biol Oceanog
  • ,
  • Niels Wellner
  • ,
  • Christian B Vægter
  • Sarah J Lincoln, Mayo Clinic
  • ,
  • Anders Nykjær
  • Nilüfer Ertekin-Taner, Mayo Clinic
  • ,
  • Jessica E Young, Univ Washington, University of Washington, University of Washington Seattle, University of Washington Tacoma, Dept Biol Oceanog
  • ,
  • Mette Nyegaard
  • Olav M Andersen

SORL1 is strongly associated with both sporadic and familial forms of Alzheimer's disease (AD), but a lack of information about alternatively spliced transcripts currently limits our understanding of the role of SORL1 in AD. Here, we describe a SORL1 transcript (SORL1-38b) characterized by inclusion of a novel exon (E38b) that encodes a truncated protein. We identified E38b-containing transcripts in several brain regions, with the highest expression in the cerebellum and showed that SORL1-38b is largely located in neuronal dendrites, which is in contrast to the somatic distribution of transcripts encoding the full-length SORLA protein (SORL1-fl). SORL1-38b transcript levels were significantly reduced in AD cerebellum in three independent cohorts of postmortem brains, whereas no changes were observed for SORL1-fl. A trend of lower 38b transcript level in cerebellum was found for individuals carrying the risk variant at rs2282649 (known as SNP24), although not reaching statistical significance. These findings suggest synaptic functions for SORL1-38b in the brain, uncovering novel aspects of SORL1 that can be further explored in AD research.

OriginalsprogEngelsk
Artikelnummer43
TidsskriftActa Neuropathologica Communications
Vol/bind9
ISSN2051-5960
DOI
StatusUdgivet - mar. 2021

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