Affiliations: [a] Molecular Signalling Group, National Research Council Canada, Institute for Biological Sciences, Ottawa, ON, Canada | [b] Department of Life and Reproduction Sciences, Histology and Embryology Section, University of Verona Medical School, Verona, Italy
Correspondence:
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Correspondence to: Dr. Balu Chakravarthy, National Research Council, 1200 Montreal Road, Bldg M-54, Institute for Biological Sciences, Ottawa, ON, K1A 0R6 Canada. Tel.: +1 613 990 0899; Fax: +1 613 941 4475; E-mail: Balu.Chakravarthy@nrc-cnrc.gc.ca.
Abstract: The pan-specific p75 neurotrophin receptor (p75NTR) 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 p75NTR and that Aβ42-accumation in two strains of transgenic AD model mice is accompanied by an increased level of hippocampal membrane-associated p75NTR (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 p75NTR. In this study, using polyclonal and monoclonal antibodies against the p75NTR receptor's intra- and extracellular domains, we show that indeed the mean level of membrane-associated p75NTR 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 p75NTR to AD cognitive decline is discussed.
