Live cell imaging of single neurotrophin receptor molecules on human neuron in Alzheimer's disease

Abstract

The changes in the receptor dynamics such as the surface movement of the receptor molecules on the plasma membrane are essential to receptor function. However, whether the receptor dynamics are affected by disease conditions is unknown. Neurotrophin receptors such as TrkA and p75NTR play a critical role in neuronal survival and their functions are highly affected in Alzheimers disease (AD). Using live-cell single-molecule imaging of neurotrophin receptors we examined the surface trafficking of TrKA and p75NTR molecules on human induced pluripotent stem cells (hiPSCs) derived live neurons from presenilin 1 (PSEN1) mutant AD patients and healthy subjects. Here we report that surface trafficking of p75NTR molecules on neurites is faster than that of TrkA molecules in healthy controls. The surface dynamics of TrkA molecules were elevated in AD patients compared to healthy individuals. In contrast, the surface movement of p75NTR was significantly smaller in AD patients compared to healthy individuals. Interestingly, amyloid beta1-42 (A{beta}1-42) administration increased the surface trafficking of both TrkA and p75NTR in healthy hiPSCs neurons. These findings provides the first evidence that the surface diffusion of TrkA and p75NTR molecules are altered in patients suffering from AD. Our data also suggest that A{beta}1-42 may responsible for the alteration of the surface movements of TrkA but not for p75NTR. One Sentence SummaryThe surface movements of neurotrophin receptors such as TrkA and p75NTR are altered in neurons derived from patients suffering from familial Alzheimers disease.