Bioinformatic Analysis of Alzheimer’s Disease Using Functional Protein Sequences

Over the past 25 years, it has become clear that the proteins forming the deposits are central to the disease process. Amyloid-ß and tau make up the plaques and tangles of Alzheimer’s disease(AD), where these normally soluble proteins assemble into amyloid-like filaments(Michel and Maria, 2006). Recently Ballatore et al. (2007) summarized the most recent advances in the mechanisms of tau-mediated neurodegeneration to forge an integrated concept of those tau-linked disease processes that drive the onset and progression of AD and related tauopathies. New evidence indicates that tau may mediate neurotoxicity by altering the organization and dynamics of the actin cytoskeleton (Gallo, 2007). Amyloid formation is a nucleation-dependent process that is accelerated dramatically in vivo and in vitro upon addition of appropriate fibril seeds (Alexander et al., 2006) AD is a progressive neurodegenerative disorder characterized by amyloid plaques composed of aggregated amyloid beta plaques, neurofibrillary tangles (NFT) composed of hyperphosphorylated tau and synaptic defects resulting in neuritic dystrophy and neuronal death (Hutton and McGowan, 2004). A growing body of evidence implicates cholesterol and cholesterol-rich membrane microdomains in amyloidogenic processing of amyloid precursor protein (APP). Chemg et al., (2007) reviewed the recent findings regarding the association of BACE1, ã-secretase and APP in lipid rafts, and discuss potential therapeutic strategies for AD that are based on knowledge gleaned from the membrane environment that fosters APP processing.