APP and Alzheimer disease: While tau pathology, most notably tau phosphorylation, is viewed as a general hallmark of TBI, a key pathological feature that distinguishes TBI-induced AD from other neurodegenerative conditions is increased production of beta amyloid peptide (Aβ).3 Generation of Aβ results from the sequential cleavage of Amyloid Precursor Protein (APP) by β- and then γ-secretase, in a process known as amyloidogenic APP cleavage.