The Lemere Lab’s research combines neuropathological, immunological, molecular and cellular, biochemical, PET imaging, and behavioral methods. Our early work focused on the mechanism of Aβ generation and its temporal cerebral deposition into amyloid-β (Aβ) plaques and blood vessels in Alzheimer’s disease (AD), Down syndrome (DS) and models thereof, including non-human primates and transgenic mouse models. That work led to preclinical testing of both active and passive Aβ vaccines in AD mouse models and non-human primates, resulting in plaque-lowering and cognitive stabilization. Currently, we are testing the efficacy of a passive vaccine targeting pathological pyroglutamate-3 Aβ in AD mouse models, and recently incorporated focused ultrasound to enhance delivery of the antibodies into brain. Our work has also demonstrated an important role for inflammation during Alzheimer’s pathogenesis in AD and DS human brain, as well as brains of non-human primates and AD mouse models, by examining the temporal accrual of amyloid-associated inflammatory proteins in relation to Aβ deposition, gliosis and neuritic changes. This work led to us to focus directly on the impact of the complement system on brain aging and neurodegeneration using knockout mouse models and more recently, to develop inducible conditional complement knockout mice. We are also investigating how AD risk-associated variants in Complement Receptor 1 (CR1) in humans affect Aβ clearance. In collaboration with BWH Radiology, we have incorporated microPET imaging of neuroinflammation into our preclinical mouse studies. In addition, we are studying the effects of deep space galactic cosmic rays on brain aging and the risk of Alzheimer’s disease in wildtype and AD mice in preparation for the first manned mission to Mars in 2030. Current and past funding sources include: NIH/NIA, NASA, the Alzheimer’s Association, the Cure Alzheimer’s Fund, the Focused Ultrasound Foundation, the BrightFocus Foundation, an anonymous foundation, and philanthropic gifts.