Components of the innate immune system such as microglia have been well studied in Alzheimer's disease (AD), but the role of lymphocytes and cells of the adaptive immune system is less well understood. In the Proceedings of the National Academy of Sciences, Blurton-Jones and colleagues develop an AD-prone mouse model deficient in lymphocytes (T cells, B cells and natural killer (NK) cells) to determine the role of the adaptive immune system in the progression of AD. These 'Rag-5xfAD' mice show greater accumulation of amyloid Ab plaques in the brain and enhanced signs of microglia activation—both signatures of AD progression. The accumulation of Ab in Rag-5xfAD mice seems to be due to an impairment in Ab phagocytosis rather than greater Ab production. Nonspecific immunoglobulins associated with microglia in lymphoreplete mice or in Rag-5xfAD that received bulk immunoglobulins seem to trigger Ab phagocytosis and clearance. These data suggest that lymphocytes can slow AD by 'dialog' with microglia and thereby facilitate Ab clearance.

Proc. Natl. Acad. Sci. USA (16 February 2016) doi:10.1073/pnas.1525466113