User:Arcticcatzl/sandbox

Disease Associations

A number of genetic, cell biology, biochemical and animal studies support the concept that Aß plays a central role in the development of Alzheimer’s disease pathology. Brain Aß is elevated in patients with sporadic Alzheimer’s disease. Aß is the main constituent of brain parenchymal and vascular amyloid, it contributes to cerebrovascular lesions and is neurotoxic. It is unresolved how Aß accumulates in the central nervous system and subsequently initiates the disease of cells. Significant efforts have been focused on the mechanisms responsible for Aß production, including the proteolytic enzymes alpha- and ß-secretases which generate Aß from its precursor protein, APP (amyloid precursor protein). Aß circulates in plasma, cerebrospinal fluid (CSF) and brain interstitial fluid (ISF) mainly as soluble Aß40    Senile plaques contain both Aß40 and Aß42, while vascular amyloid is predominantly the shorter Aß40. Several sequences of Aß were found in both lesions. Generation of Aß in the CNS may take place in the neuronal axonal membranes after APP-mediated axonal transport of ß-secretase and presenilin-1.