Hippocampal membrane-associated p75NTR levels are increased in Alzheimer’s disease

The pan-specific p75 neurotrophin receptor (p75NTR) is believed to play an important role in the pathogenesis of Alzheimer’s disease. It is involved in mediating amyloid-ß (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 p75NTR and that Aβ42-accumation in two strains of transgenic Alzheimer disease (AD) model mice is accompanied by an increased level of hippocampal membrane-associated p75NTR (Chakravarthy et.al. J Alzheimer’s Dis 19, 915-925). This raised an important question whether accumulating Aβ42 in human AD is also accompanied by an increased hippocampal membrane-associated p75NTR. In this study, using polyclonal and monoclonal antibodies against the p75NTR receptor’s intra- and extra-cellular domains, we show that indeed the mean level of membrane-associated p75NTR in the hippocampal formation is significantly higher (~ two-fold, p < .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 p75NTR to AD cognitive decline is discussed.