Alzheimer’s disease is a progressive age-associated neurodegenerative disease, characterised by the presence of two key neuropathological hallmarks; amyloid-β plaques and neurofibrillary tangles. Understanding how amyloid-β behaves “in vivo” prior to symptomatic onset is an important question that has previously only been inferred by peripheral measurements (CSF, PET). Here we use human brain slice cultures to model aspects of amyloid-β AD pathology, by both assessing how endogenous properties and pathology relate to patient characteristics, and by induced perturbations using pharmacological treatment.“Healthy” peri-tumour access tissue from surgical resections for brain tumour removal were sectioned and cultured for up to 7 days in vitro (DIV). Basal production of amyloid-β and tau protein was assessed in comparison to patient characteristics. Slices were treated with amyloid-pathway modulators to see the impact on endogenous protein production (amyloid-β and tau). Slices were histologically screened for endogenous tau and amyloid-β pathology.Amyloid-β40 released into media decreased with age of patient. Tau release was increased in temporal brain tissue compared to frontal brain tissue. BACE1 inhibitor and Phosphoramidon application bi-directionally manipulated levels of amyloid-β40 and 42 levels in culture medium. Endogenous AD-associated pathology was also visible in a subset of patients for at least 7 DIV, associated with age of patient.This system provides a unique opportunity to study AD in a developmentally mature and functional human system with endogenous protein expression and pathology. Amyloid-β production was shown to be manipulable, suggesting this method can be used for further therapeutic testing.