The amyloid precursor protein of Alzheimer disease in human brain and blood

Studies of the metabolism and function of the amyloid precursor protein (AP P) and its proteolytic fragment AP in cultured cells, transgenic mice, and post-mortem brain tissue have advanced our understanding of Alzheimer disea se (AD), However, the molecular pathogenesis of the disease is still not cl ear, and we are a long way from finding a cure for the disease, Studies car ried out on human platelets and leukocytes have also helped shed light on A PP and AP metabolism and function. Platelet and leukocyte APP isoforms are processed using mechanisms similar to those in neuronal cells to generate A P and soluble forms of APP The activation of platelets and leukocytes leads to the secretion of APP and AP, resulting in higher levels of these protei ns in serum, APP and AP in the circulation may be involved in the regulatio n of platelet function and in the modulation of immune responses, Because h uman platelets and lymphocytes produce all forms of APP and secrete amyloid ogenic AP peptides, these tissues may be useful in monitoring responses to therapeutic interventions directed at APP metabolism, Although not of neuro nal origin, further studies on the more accessible ex vivo tissues, includi ng platelets and leukocytes and other blood components, may reveal potentia l peripheral markers for AD and will further our understanding of the molec ular pathogenesis of AD.