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Secretion of VGF is increased in cerebrospinal fluid and blood in neurodegenerative disorders like Alzheimer's disease (AD) and VGF is a potential biomarker for these disorders. We have shown that VGF is expressed in peripheral T cells and is correlated with T cell survival and cytokine secretion. The frequency of VGF+CD3+ T cells increases with normal aging. We found an increased number of VGF-expressing T cells in patients with AD compared to aged healthy controls, which was associated with enhanced HbA1c levels in blood. Upon treatment with rivastigmine, T cell proliferation and VGF expression in AD patients decreased to the level found in controls. Moreover, rapamycin treatment in vitro reduced the number of VGF+CD3+ cells in AD patients to control levels.

VGF is a protein expressed by neurons and processed into several peptides. It plays a role in energy homeostasis and promotes growth and survival. Recently, VGF mRNA was detected in peripheral leukocytes. Since it is known that aging is associated with a decrease in the development and function of neuronal as well as immune cells, we addressed the question whether a peripheral expression of VGF by CD3+ T cells and CD56+ NK cells is correlated with age. Therefore, the frequency of VGF+CD3+ and VGF+CD56+ cells was determined in mentally healthy volunteers aged between 22 and 88. We found an age-dependent increase in the number of VGF+CD3+ T cells that correlated with HbA1c and the body mass index (BMI). VGF-expression by NK cells was age-independent. Blockade of VGF reduced proliferation and secretion of cytokines such as IL-2, IL-17A, IL-1β, IL-10 and TNF by CD3+ T cells and PBMCs. Rapamycin-mediated T cell blockade significantly reduced the frequency of VGF-expressing T cells. We conclude that VGF contributes to survival and function of peripheral T cells. The age-dependent increase in VGF-expression could serve as mechanism that counterregulates the decrease in functionality of T lymphocytes.