Hippocampal membrane-associated p75 NTR levels are increased in Alzheimer's disease

B Chakravarthy, M Ménard, S Ito… - Journal of …, 2012 - content.iospress.com
B Chakravarthy, M Ménard, S Ito, C Gaudet, I Dal Prŕ, U Armato, J Whitfield
Journal of Alzheimer's Disease, 2012content.iospress.com
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 …
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.
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