There are two major pathological lesions in AD brain: intracellular inclusions of tau protein
in the form of neurofibrillary tangles, and extracellular plaque formation by accumulations
of amyloid beta peptide (Aβ) derived from the β-amyloid precursor protein (APP).
Accumulating Aβ, a proteolytic byproduct of amyloid precursor protein (APP) metabolism,
is an important aspect of AD pathology. APP is processed by two competing pathways, the
amyloidogenic pathway through β-secretase (BACE1) and γ-secretase, which produce β-
APPs and Aβ40/Aβ42 peptides, and the predominant non-amyloidogenic pathway via α-
secretase, which produces neuroprotective α-APPs and several non-amyloidogenic peptides
[138]. The sex-specific neuropathology in AD has been reported by neuroimaging and
postmortem human studies, such as men with AD have more pronounced pathology in the
right hemisphere, whereas women with AD often have more manifested pathology than
male AD patients [139; 140].