Autoantibodies in Type-2 Diabetes having Neurovascular Complications Bind to the Second Extracellular Loop of the 5-Hydroxytryptamine 2A Receptor.

Diabetes is associated with a substantially increased risk of certain neurovascular and neurodegenerative complications, e.g. stroke, dementia, Parkinson’s disease, major depressive disorder [1], through complex and poorly-defined mechanisms. We previously reported the occurrence of activating 5-HT2A receptor IgG autoantibodies in plasma or serum from older adult diabetes suffering with major depressive disorder [2], Parkinson’s disease or dementia [3]. Acute neurite retraction and accelerated mouse neuroblastoma N2a cell death induced by the autoantibodies in cell culture was partially or completely prevented by co-incubation (of IgG autoantibodies) with selective antagonists of the 5-HT2A receptor [2,3].