The two pathological hallmarks of AD are extracellular plaques and intracellular tangles. Plaques are formed mostly from the deposition of amyloid beta (Ab) a peptide derived from amyloid precursor protein (APP). The metabolic processing of APP that results in Ab formation requires two enzymatic cleavage events, a b-secretase cleavage by the aspartyl protease beta-site APP-cleaving enzyme (BACE) and a g-secretase cleavage dependent on presenilin. Single beta-amyloid peptides, after misfolding, can aggregate and form fibrils and successively plaques. Filamentous neurofibrillary tangles (NTF) are formed from paired helical filaments composed of hyperphosphorylated tau protein, a microtubule-associated protein.