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 investigated if VGF is expressed in T-lymphocytes and if this correlates to pharmacological treatment in AD.

It is common knowledge that aging is associated with a decrease of development and function in neuronal and immune cells alike. Here we investigate whether a peripheral expression of VGF by CD3+ T cells is correlated with age. We asked, if there is a difference between the number of VGF-expressing T cells in patients with AD compared to aged healthy controls and upon treatment with rivastigmine.

We extracted peripheral blood mononuclear cells (PBMCs). In the first study we compared 42 healthy participants (aged 22 to 88) for their level of VGF. In the second study we compared VGF levels from 24 AD patients with 14 healthy controls.

We found an age-dependent increase in the number of VGF+ CD3+ T cells that correlated with HbA1c and the BMI. Blockade of VGF reduced proliferation and secretion of different cytokines and TNF by CD3+ T cells and PBMC´s. Rapamycin-mediated T cell blockade significantly reduced the frequency of VGF-expressing T cells.

We found an increased number of VGF-expressing T cells in patients with AD compared to healthy controls. Upon treatment with rivastigmine, T cell proliferation and VGF expression in AD patients decreased to the level found in controls.

The age- and AD patients-dependent increase in VGF-expression could serve as a mechanism that counterregulates the decrease in functionality of T-lymphocytes or deficits in case of AD.

We conclude that VGF contributes to survival and function of peripheral T cells. Our results suggest that VGF serves as a potential biomarker for early detection of AD and for monitoring a treatment with rivastigmine.