T Lymphocytes in the Pathogenesis and Progression of Alzheimer's Disease: Pursuing Direct Neuropathological Evidence.

Multiple studies have proposed important roles of T cells in the pathogenesis of Alzheimer's disease. Given the successful application of immune-based therapy for cancer and a variety of diseases, T cell-modifying therapy becomes an attractive way to develop new therapies for Alzheimer's disease and perhaps neurodegenerative diseases in general. However, most of these studies address peripheral T cell responses, while direct pathological evidence documenting T cell infiltration relative to Alzheimer's disease pathological markers (i.e., amyloid plaque and neurofibrillary tangle) is sparse and at best, very preliminary in both human subjects and relevant animal models. Here, we concisely summarize the available pathological data that directly corresponds to T cell infiltration, critically analyze the current knowledge gaps, and thoughtfully propose several key recommendations for future research.