Novel Contribution of Secreted Amyloid- β Precursor Protein to White Matter Brain Enlargement in Autism Spectrum Disorder

Conclusion Brain overgrowth is a consistent endophenotype in 20% of individuals with autism. MRI volumetric studies showed overgrowth for both gray and white matter for young children (ages 2–6) with autism, coincidental to presentation of autistic symptoms. The trajectory of brain growth slows in adolescence and may show decreased growth at older ages. Enlargement of brain matter in autism may be due to a combination of elevated metabolic processes, migrational abnormality, and/or neuroinflammation. Recognizing potential contribution of the non-amyloidogenic pathway of βAPP processing to brain enlargement in autism enables novel adaptation of long-known AD pathway analyses to autism. Increased sAPPα and the ADAM family α-secretases may directly increase oligodendrocyte myelination or the neuroinflammatory response that promotes axonal sprouting of neurons and astrocyte activation. Consequently sAPPα and the ADAM family α-secretases, activated ERK receptor signaling, can activate P13K/AKt/mTOR. Resulting activation of Rho GTPases would favor OPC stimulation, thus enhancing myelination by activation of cofilin. Identification of new roles for AD pathways in autism may lead to new treatments for this enigmatic disorder. Author Contributions All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication. Funding We thank grant supports from the National Institute o...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research