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

• Published in: Cellular and molecular neurobiology Vol. 22; no. 2; pp. 139 - 152
• Main Authors: Fatemi, S Hossein, Stary, Joel M, Egan, Elizabeth Ann
• Format: Journal Article
• Language: English
• Published: United States 01-04-2002
• Subjects: Adult; Age Factors; Autistic Disorder - blood; Autistic Disorder - genetics; Autistic Disorder - psychology; Cell Adhesion Molecules, Neuronal - blood; Cell Adhesion Molecules, Neuronal - deficiency; Cell Adhesion Molecules, Neuronal - genetics; Cerebellum - metabolism; Cerebellum - pathology; Cerebellum - physiopathology; Child; Child, Preschool; DNA Mutational Analysis; Extracellular Matrix Proteins - blood; Extracellular Matrix Proteins - deficiency; Extracellular Matrix Proteins - genetics; Female; Genetic Predisposition to Disease - genetics; Genetic Testing; Humans; Male; Middle Aged; Molecular Weight; Nerve Tissue Proteins; Polymorphism, Genetic - genetics; Protein Isoforms - genetics; Serine Endopeptidases; Sex Factors; Twin Studies as Topic
• ISSN: 0272-4340
• DOI: 10.1023/A:1019857620251

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.