Accumulation of a repulsive axonal guidance molecule RGMa in amyloid plaques: a possible hallmark of regenerative failure in Alzheimer's disease brains

Neuropathology and Applied Neurobiology
J SatohK Arima

Abstract

RGMa is a repulsive guidance molecule that induces the collapse of axonal growth cones by interacting with the receptor neogenin in the central nervous system during development. It remains unknown whether RGMa plays a role in the neurodegenerative process of Alzheimer's disease (AD). We hypothesize that RGMa, if it is concentrated on amyloid plaques, might contribute to a regenerative failure of degenerating axons in AD brains. By immunohistochemistry, we studied RGMa and neogenin (NEO1) expression in the frontal cortex and the hippocampus of 6 AD and 12 control cases. The levels of RGMa expression were determined by qRT-PCR and Western blot in cultured human astrocytes following exposure to cytokines and amyloid beta (Aβ) peptides. In AD brains, an intense RGMa immunoreactivity was identified on amyloid plaques and in the glial scar. In the control brains, the glial scar and vascular foot processes of astrocytes expressed RGMa immunoreactivity, while oligodendrocytes and microglia were negative for RGMa. In AD brains, a small subset of amyloid plaques expressed a weak NEO1 immunoreactivity, while some reactive astrocytes in both AD and control brains showed an intense NEO1 immunoreactivity. In human astrocytes, transforming g...Continue Reading

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Citations

Apr 2, 2014·Alzheimer's Research & Therapy·Jun-Ichi SatohKunimasa Arima
Jan 23, 2016·Progress in Neurobiology·Lana M OsbornElly M Hol
Apr 28, 2017·Alzheimer's Research & Therapy·Yan-Shi HuJu Wang
Mar 23, 2021·In Vitro Cellular & Developmental Biology. Animal·Alinne do Carmo CostaErika Cristina Jorge

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