The Role of T Cells in Alzheimer's Disease Pathogenesis.

ABSTRACT

Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with memory decline and cognitive impairment, which is related to hallmark protein aggregates, amyloid-ß (Аß) plaques and neurofibrillary tangles; the latter are accumulated with hyperphosphorylated Tau protein. Immune cells play an important role in AD pathogenesis. Although the role of T cells in AD remains controversial, studies have shown that T cell deficiency is associated with increased AD pathology. In contrast, transplantation of T cells reduces AD pathology. T cells can help B cells generate anti-Ðß antibody to neutralize the toxin of Ðß and hyperphosphorylated Tau. T cells also activate macrophages to phagocytose misfolded proteins including Ðß and Tau. Recent data have also shown that AD animals have a damaged thymic microenvironment, especially thymic epithelial cells (TECs), resulting in decreased T cell numbers, which contribute to AD pathology. Therefore, regulation of T cell regeneration, for example by rejuvenating the thymic microenvironment, has the potential to be used in the treatment of AD.