title: Hippocampal membrane-associated p75NTR 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 Aβ(42) increases the level of membrane-associated p75(NTR) and that Aβ(42)-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 Aβ(42) 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.
authors.affiliation: Molecular Signalling Group, National Research Council Canada, Institute for Biological Sciences, Ottawa, ON, Canada. Balu.Chakravarthy@nrc-cnrc.gc.ca
authors.forename: Balu
authors.initials: B
authors.lastname: Chakravarthy
authors.forename: Michel
authors.initials: M
authors.lastname: Ménard
authors.forename: Shingo
authors.initials: S
authors.lastname: Ito
authors.forename: Chantal
authors.initials: C
authors.lastname: Gaudet
authors.forename: Ilaria
authors.initials: I
authors.lastname: Dal Prà
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Armato
authors.forename: James
authors.initials: J
authors.lastname: Whitfield
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D020800:Receptor, Nerve Growth Factor