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Reduced Blood Levels of Reelin as a Vulnerability Factor in Pathophysiology of Autistic Disorder
Open accessAbstract
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.
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Metadata
- Authors
- Fatemi, S. H., Stary, J. M., & Egan, E. A.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Fatemi, S. Hossein
- ORCID
- Fatemi, S. Hossein
- Venue
- Cellular and Molecular Neurobiology
- Published
- 2002-04
- Volume
- 22
- Issue
- 2
- Pages
- 139-152
- ISSN
- 0272-4340 (ISSN-L)
- 1573-6830
- PMC
- PMC11533798
- OpenAlex
- W1503707236
- Cited by
- 122
- References
- 38
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 1 · 2021: 5 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 5 · 2015: 10 · 2014: 6 · 2013: 7 · 2012: 7
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Cellular and Molecular Neurobiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
- Keywords
- reelin, autism spectrum disorder, first-degree relatives, vulnerability factors, cerebellum, albumin, ceruloplasmin, neurodevelopmental disorders
- MeSH terms
- Reelin Protein, Adult, Age Factors, Autistic Disorder, Cerebellum, Child, Child, Preschool, DNA Mutational Analysis, Female, Genetic Testing, Humans, Male, Middle Aged, Molecular Weight, Nerve Tissue Proteins, Polymorphism, Genetic, Serine Endopeptidases, Sex Factors, Cell Adhesion Molecules, Neuronal, Extracellular Matrix Proteins, Twin Studies as Topic, Genetic Predisposition to Disease, Protein Isoforms
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