Chronic neuroinflammation contributes detrimentally to the pathology of Alzheimer's disease (AD), wherein synaptic transmission is diminished, leading to severe cognitive decline. Microglia immune cells drive a number of neuroinflammatory responses, such as release of pro-inflammatory mediators and clearance of beneficial targets (such as pathogens), via phagocytosis. In AD, build-up of excessive amyloid-beta (Aβ) may impact the ability of microglia to efficiently clear such beneficial targets. Previous work has shown that the microglial nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1), a driver of pro-inflammatory cellular functions, may also be involved in phagocytic regulation. Inhibition of PARP-1 has been shown to have no impact on beneficial phagocytosis of Aβ targets in conditions representing health. However, whether this beneficial phagocytosis is maintained in the context of amyloidopathy (to mimic one component of AD pathology), has not been examined. PARP-1 has also been shown to act in concert with Ca2+ permeable TRPM2 (Transient Receptor Potential Melastatin 2) channels. In this study, we investigate whether amyloidopathy influences microglial phagocytosis of fluorescently labeled Aβ (FAM-Aβ) and if so, the extent to which the pro-inflammatory PARP-1/TRPM2 signalling pathway is involved. This data shows that PARP-1 and TRPM2 do not have a role in the uptake of Aβ in homeostatic conditions. Further, although amyloidopathy compromises the ability of microglia to engulf Aβ, inhibition of PARP-1 or TRPM2 does not further compromise Aβ clearance by microglia. Thus, a therapeutic targeting the inhibition of PARP-1/TRPM2 in homeostatic conditions should not have any negative effects such as decreased Aβ phagocytosis.