APP

Role in the organism:

The APP gene encodes a widely present protein located on the cell surface. The gamma secretase protein complex consisting of Presenilin 1 and 2 proteins (see PSEN1 gene on chromosome 14 and PSEN2 gene on chromosome 1) cleaves this protein. The consequence of this is the release of an intracellular protein fragment that can react with nuclear proteins and a histone-modifying enzyme. The normal function of the APP gene product may therefore be the regulation of gene expression.

Role in the disorder (state):

Another fragment of the processed APP protein is the beta-amyloid protein. It is released from the cell surface and can react with receptors on other cells. Accumulation of beta-amyloid plaques in the brain and beta-amyloid fibrils within neurons is a major feature of Alzheimer's disease, a progressive neurodegenerative disease of aging. Mutations in the APP gene can predispose individuals to the onset of Alzheimer's disease by promoting beta-amyloid plaque aggregation in these abnormal structures. Mutations in the PSEN1 and PSEN2 genes are also one of the possible causes of this disease. Similar plaques accumulate in elderly patients with Down syndrome, probably reflecting increased doses of this gene product in the brain.