Alzheimer’s disease (AD) is characterized by the degeneration of brain networks involved in cognitive function. AD mouse models are used to study disease pathogenesis, but no single model fully captures the pathological changes in AD patients. Thus, extensive validation of AD therapeutic targets in multiple animal models is required before advancing to clinical research. Huang et al. determined that the absence of the G protein–coupled receptor 3 (GPR3), a protein present in the brain, alleviated the cognitive deficits and reduced amyloid pathology in four different disease-relevant mouse models of AD. Furthermore, the abundance of GPR3 was increased in postmortem brain tissue from a subset of AD patients. This study indicates that GPR3 is a potential AD therapeutic target.
Y. Huang, A. Skwarek-Maruszewska, K. Horré, E. Vandewyer, L. Wolfs, A. Snellinx, T. Saito, E. Radaelli, N. Corthout, J. Colombelli, A. C. Lo, L. Van Aerschot, Z. Callaerts-Vegh, D. Trabzuni, K. Bossers, J. Verhaagen, M. Ryten, S. Munck, R. D’Hooge, D. F. Swaab, J. Hardy, T. C. Saido, B. De Strooper, A. Thathiah, Loss of GPR3 reduces the amyloid plaque burden and improves memory in Alzheimer’s disease mouse models. Sci. Transl. Med. 7, 309ra164 (2015). [Abstract]