Background: Alzheimer's disease (AD) is the most common form of dementia and neuropathologically characterized by the presence of neurofibrillary tangles and the deposition of β-amyloid (Aβ) in neuritic plagues. So far three genes have been identified that, when mutated, cause early onset AD: Amyloid precursor protein (APP), Presenilin-1 (PS1), and Presenilin-2 (PS2). Nicastrin is a transmembrane glycoprotein whose mutation causes a type of familial Alzheimer's disease (FAD). This protein forms gamma-secretase complex with PS1, PS2, APH-1, PEN-2 and catenins, which is involved in proteolytically processing APP to the short AD-associated peptide β-amyloid. Another well-known substrate of gamma-secretase is Notch. It has been shown that mouse Nicastrin deficiency causes neurodegeneration recently.
Date:
2014-07
Relation:
Alzheimer's and Dementia. 2014 Jul;10(4, Suppl.):P786.
