Characterization of the Pathological and Biochemical Markers that Correlate to the Clinical Features of Autism
Abstract
In this program project, 56 brains were examined, including 22 brains of subjects with idiopathic autism(unknown etiology), 12 brains of individuals with autism associated with chromosome15 duplication (dup15) and 22 brains of control subjects from 2 to 65 years of age. The study of a global pattern of brain developmental abnormalities integrates results of morphometric study of 17 brain structures in autistic and control subjects. Significant similarities of developmental alterations of neuronal proliferation, migration, and cytoarchitecture in idiopathic autism and autism caused by dup(15) indicate that, in part, developmental defects are caused by similar mechanisms regardless of the etiological factor. However, (a) the absence of cortical dysplasia, (b) presence of a several fold more frequent pathology in the dentate gyrus, (c) more intraneuronal A in neurons, (d) a very high prevalence of early onset of seizures in individuals with autism dup(15) compared to the idiopathic autism subjects indicate that the etiology has a specific contribution to structural, biochemical and functional changes in autism. Striking brain region specific delays of neuronal growth in children 3-8 years of age, indicate that autism is caused by failure of mechanisms controling neuron and brain growth. Regional dysregulation results in desynchronization of growth of interacting neurons, neuronal circuits, and neurotransmitter systems. Mapping of these abnormalities to structures with their known role in social behavior, communication, and stereotypic behavior results in identification of a structural component of functional deficits observed in clinical studies. Enhanced APP processing with - and -secretases, leading to enhanced accumulation ofA in neuronal cytoplasm observed in the majority of autistic subjects, including children, is an early sign of an altered non-amyloidogenic pathway of APP processing.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2011
- Accession Number
- ADA556211
Entities
People
- Jerzy Wegiel
- Ted Brown
Organizations
- Research Foundation For Mental Hygiene