However, in contrast to Alzheimer's disease, levels of the antimicrobial peptide beta-amyloid are decreased and the levels of the neurotrophic/myelinotrophic soluble APP alpha are increased in autism, together with an increased activity of α-secretase. sAPPα induces an increase in glutamatergic and a decrease in GABA-ergic synapses creating and excitatory/inhibitory imbalance that has also been observed in autism.
The method is useful for identifying the defective APP-mRNA isoform in LND patients, and in neurodevelopmental and neurodegenerative disorders in which the APP gene is involved in the pathogenesis of diseases such as autism, fragile X syndrome, amyotrophic lateral sclerosis, and Alzheimer's disease, and may pave the way for new strategies applicable to rational antisense drugs design.
Amyloid precursor protein (APP) is involved in neuronal development and APP dysregulation has been implicated in the pathophysiology of other developmental disorders including fragile X syndrome and idiopathic autism.
My findings accounted for epigenetic mechanism in the regulation of alternative APP pre-mRNA splicing as well as for epigenetic control of genomic rearrangements of APP gene may provide therefore new directions not only for investigating the role of APP in neuropathology associated with HGprt-deficiency in LNS and LNVs patients but also for the research in neurodevelopmental and neurodegenerative disorders by which APP gene involved in the pathogenesis of the diseases such as autism, fragile X syndrome (FXS), and Alzheimer's disease (AD) with its diversity and complexity, especially for sporadic form of AD (SAD).
Large and rare copy number variants (CNVs) are known to confer risk in several related disorders including Alzheimer's disease (at APP), schizophrenia, epilepsy, mental retardation, and autism.
Elevated levels of secreted amyloid precursor protein-alpha (sAPPα), the product of α-secretase cleavage of APP, are found in the plasma of some individuals with autism.