Effect of Gpnmb gene on memory deficits in 9 month-old 5xFAD mice

The onset and progression of Alzheimer's disease (AD) correlate with neuroinflammatory processes, and inflammatory microglia (MG) are associated with AD-like pathology in a transgenic mouse model. GPNMB was identified as a marker for one subtype (type 1) of rat primary MG (Kawahara et al., GLIA, 2016). However, the function of GPNMB+ type 1 MG in AD brain are largely unknown. We recently reported that memory deficits in 9 month-old APP23 mice, one of the amyloid precursor protein transgenic mice, was reduced in Gpnmb gene heterozygosity (APP23;Gpnmb+/-, 92ndAnnual meeting of the Japanese Pharmacological Society, 2-O-04, 2019). In the present study, we investigated whether Gpnmb gene heterozygosity could affect on memory deficits in 9-month old 5xFAD mice, other AD model mice. We used 5xFAD mice backcrossed to C57BL/6J mice at least for ten generation. Spatial learning and memory was evaluated by Morris Water Maze test. We observed that the number of Nissl-positive neurons in subiculum of 5xFAD mice were lower than those in their wild type littermates. We observed that AD-related memory deficits in 9 month-old 5xFAD mice were decreased in Gpnmb gene heterozygosity (5xFAD;Gpnmb+/-). These finding suggest that GPNMB-positive type 1 MG may be related to memory deficits in AD.