APP

The APP gene provides instructions for making a protein called amyloid precursor protein. This protein is found in many tissues and organs, including the brain and spinal cord (central nervous system). Little is known about the function of amyloid precursor protein. Researchers speculate that it may bind to other proteins on the surface of cells or help cells attach to one another.

Amyloid precursor protein is cut by enzymes to create smaller fragments (peptides), some of which are released outside the cell. Two of these fragments are called soluble amyloid precursor protein (sAPP) and amyloid beta peptide. Recent evidence suggests that sAPP has growth-promoting properties and may play a role in the formation of nerve cells (neurons) in the brain both before and after birth. Other functions of sAPP and amyloid beta peptide are under investigation.

Alzheimer disease - caused by mutations in the APP gene

More than 25 different mutations in the APP gene can cause early-onset Alzheimer disease. These mutations are responsible for 10 percent to 15 percent of all early-onset cases of the disorder.

The most common APP mutation changes one of the protein building blocks (amino acids) in the amyloid precursor protein. This mutation replaces the amino acid valine with the amino acid isoleucine at protein position 717 (written as Val717Ile or V717I). Mutations in the APP gene can lead to an increased amount of the amyloid beta peptide or to the production of a slightly longer and stickier form of the peptide. When these protein fragments are released from the cell, they can accumulate in the brain and form clumps called amyloid plaques. These plaques are characteristic of Alzheimer disease. A buildup of toxic amyloid beta peptide and amyloid plaques may lead to the death of neurons and the progressive signs and symptoms of this disorder.

other disorders - caused by mutations in the APP gene

Certain mutations in the APP gene can also result in brain abnormalities other than Alzheimer disease. For example, a particular APP mutation causes a disorder called hereditary cerebral hemorrhage with amyloidosis-Dutch type. This disorder is characterized by recurring episodes of bleeding in the brain (hemorrhagic strokes) that lead to the deterioration of memory, concentration, and judgment. Most people with this disorder develop signs and symptoms in mid-adulthood. The mutation that causes this disorder replaces the amino acid glutamic acid with the amino acid glutamine at position 22 of amyloid precursor protein (written as Glu22Gln or E22Q). The E22Q mutation likely affects processing of this protein, leading to the formation of amyloid plaques in brain tissue and the walls of blood vessels that serve the brain.