Development of accurate biomarkers in the Alzheimer’s disease (AD) macaque model remains unattainable, in part because which aspects of macaque aging truly reflect comparable aspects of AD pathophysiology is unclear. To assess neuropathologic evidence underpinning biomarker development in macaques, we quantified ß-amyloid, pTau (AT8), neuroinflammatory marker and p16-expression in aging macaques (n=10) and AD patients (n=5). We assigned AD neuropathologic (ADNP) scores according to consensus guidelines. Further, we examined expression of pT217 and pT181 markers, acetylcholinesterase, tyrosine hydroxylase, SV2A and iron in macaque brain. Neuritic plaques containing altered expression of these markers occurred in elderly macaques and β-amyloid load, A scores and C scores approximated those in AD patients with lower ADNP scores. Amyloid load was assessed as sufficiently robust to be potentially detected by imaging in sufficiently aged animals. Braak scores in AD patients far exceeded those in macaques, whose Tau pathology was largely associated with amyloid plaques, and otherwise limited to pretangles in locus coeruleus and hippocampus. In comparison to AD patients, we suspect that Tau load in macaques falls below the limit of detection of existing Tau PET tracers. In frozen tissue, robust age-related expression of Tau-AT8, and weaker expression of Tau-pS217 was evident in neuronal bodies and processes of AD-vulnerable limbic and cortical areas that also expressed high levels of acetylcholinesterase and ß-amyloid, thus providing a neuroanatomical basis for susceptibility of these regions to AD pathology. Our data support use of the aging macaque as a powerful spontaneous model of events accompanying preclinical AD pathophysiology.