Hippocampal Membrane-Associated p75 NTR Levels are Increased in Alzheimer's Disease

Abstract

The pan-specific p75 neurotrophin receptor (p75^NTR) is believed to play an important role in the pathogenesis of Alzheimer's disease (AD). It is involved in mediating amyloid-β (Aβ) toxicity and stimulating amyloidogenesis. In addition, we have recently shown that stimulating cultured SH-SY5Y human neuroblastoma cells with Aβ₄₂ increases the level of membrane-associated p75^NTR and that Aβ₄₂-accumation in two strains of transgenic AD model mice is accompanied by an increased level of hippocampal membrane-associated p75^NTR (Chakravarthy et al. J Alzheimers Dis 19, 915-925, 2010). This raised an important question whether accumulating Aβ₄₂ in human AD is also accompanied by an increased hippocampal membrane-associated p75^NTR. In this study, using polyclonal and monoclonal antibodies against the p75^NTR receptor's intra- and extracellular domains, we show that indeed the mean level of membrane-associated p75^NTR in the hippocampal formation is significantly higher (~two-fold, p < 0.03) in human AD brains than in identical samples of hippocampal formation in age-matched non-AD human brains. The possible relation of this elevated hippocampal p75^NTR to AD cognitive decline is discussed.