Reduced blood levels of reelin as a vulnerability factor in pathophysiology of autistic disorder

S. Hossein Fatemi, Joel M. Stary, Elizabeth Ann Egan

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99 Scopus citations

Abstract

1. Autism is a severe neurodevelopmental disorder with potential genetic and environmental etiologies. Recent genetic linkage reports and biochemical analysis of postmortem autistic cerebellum point to Reelin, an important secretory extracellular protein, as being involved in the pathology of autism. 2. We hypothesized that blood levels of Reelin and its isoforms would be altered in autistic twins, and their first degree relatives versus normal controls. 3. We measured blood levels of unprocessed Reelin (410 kDa) and its proteolytic cleavage products (Reelins 330 and 180 kDa) as well as albumin and ceruloplasmin in 28 autistic individuals, their parents (13 fathers, 13 mothers), 6 normal siblings, and 8 normal controls using SDS-PAGE and western blotting. 4. Results indicated significant reductions in 410 kDa Reelin species in autistic twins (-70%, p < 0.01), their fathers (-62%, p < 0.01), their mothers (-72%, p < 0.01), and their phenotypically normal siblings (-70%, p < 0.01) versus controls. Reelin 330 kDa values did not vary significantly from controls. Reelin 180 kDa values for parents (fathers -32% p < 0.05 vs. controls, mothers -34%) declined when compared to controls. In contrast autistic Reelin 180 kDa increased, albeit nonsignificantly versus controls. Albumin and ceruloplasmin values for autistics and their first degree relatives did not vary significantly from controls. There were no significant meaningful correlations between Reelin, albumin and ceruloplasmin levels, age, sex, ADI scores, or age of onset. 5. These results suggest that Reelin 410 deficiency may be a vulnerability factor in the pathology of autism.

Original languageEnglish (US)
Pages (from-to)139-152
Number of pages14
JournalCellular and Molecular Neurobiology
Volume22
Issue number2
DOIs
StatePublished - Apr 2002

Bibliographical note

Funding Information:
We are grateful to Minnesota Medical Foundation, Kunin Fund of St. Paul Foundation, Stanley and NARSAD Foundations for provision of funds to carry out this project. We are grateful to Dr Andre M. Goffinett for his generous gift of anti-Reelin antibody. We acknowledge the generous gift of sera provided by autistic individuals and their families through the AGRE consortium. We are thankful to Ms Janet Holland for dedicated secretarial assistance.

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

Keywords

  • Autism
  • Blood
  • Reelin
  • Schizophrenia
  • Twins
  • Western blotting

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