Amyloid precursor protein

Amyloid precursor protein (APP) is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons. Its primary function is not known, though it has been implicated as a regulator of synapse formation, neural plasticity, and iron export. APP is best known as the precursor molecule whose proteolysis generates beta amyloid (Aβ), a 39- to 42-amino acid peptide whose amyloid fibrillar form is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients.

Structure

The amyloid precursor protein is a type I transmembrane glycoprotein. It is concentrated in the synapses of neurons and its role is not completely understood. The human APP gene is located on chromosome 21 and includes 18 exons spanning 290 kilobases. The gene encodes several isoforms of APP, ranging from 365 to 770 amino acids in length.

Function

The function of APP is not fully understood. Some evidence suggests that APP functions in neuronal development, specifically in neurite growth and in synapse formation. Other evidence suggests that APP may be involved in cell signaling. APP has also been implicated in the maintenance of iron homeostasis.

Role in disease

APP is cleaved by a series of enzymes, the beta-secretase and gamma-secretase, to generate beta amyloid (Aβ), a 39- to 42-amino acid peptide whose amyloid fibrillar form is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients. The accumulation of these plaques is thought to play a role in the pathogenesis of Alzheimer's disease.

See also

• Alzheimer's disease
• Beta amyloid
• Beta-secretase
• Gamma-secretase
• Amyloid plaques