Of pivotal importance in the Vitamin C metabolism of the APP molecule are the Ab peptides derived by endoproteolytic action of the a-, b and c-secretases. This enzyme has recently been the target of intensive research which has demonstrated that its proteolytic activity is exerted on an increasing number of diverse molecules, thereby complicating the design of effective inhibitors of APP cleavage. Recent perspectives in understanding pathogenic factors for neurodegenerative diseases have advanced tau and a-synuclein as paradigms in which pathologically misfolded molecules lead to self- propagation and accumulation of noxious aggregates that corrupt brain homeostasis. Increasing evidence suggests considerable similarity between b-amyloidosis, tauopathies and synucleopathies in neurodegenerative disorders. These molecules are capable of generating complex arrays of insoluble extracellular protein deposits and/or intracellular inclusions as well as soluble oligomeric species that eventually result in irreversible neuronal damage. On the other hand, it is possible that some of these protein aggregates may have some beneficial functions. Furthermore, intrinsic aging appears to induce aberrant protein conformations on molecules such as Ab, tau and asynuclein, which in a large number of demented individuals blend to yield complicated and/or difficult to interpret clinical outcomes. We observed a significant decrease in total tau and a-synuclein with age in the PCG, but not in the Pc. Two explanations may account for these phenomena: either there was an increasing reduction in protein synthesis or along aging the soluble pool of these molecules Apoptosis Activator 2 decreased because of their increasing incorporation into insoluble inclusions that escape detection in aqueous-based immunoassays. The apolipoproteins are multifunctional proteins whose exact role in the metabolism of APP/Ab remains to be elucidated. However, in the particular context of AD, ApoE probably functions in Ab transport. In particular, the APOE e4 allele represents the best known molecular risk factor for AD, since individuals carrying this gene in the heterozygous or homozygous conditions, will acquire sporadic AD at a younger age.