p75 reduces β-amyloid-induced sympathetic innervation deficits in an Alzheimer's disease mouse model

beta-Amyloid (A beta) has adverse effects on brain cells, but little is known about its effects on the peripheral nervous system in Alzheimer's disease ( AD). Several lines of in vitro evidence suggest that the neurotrophin receptor p75 mediates or exacerbates A beta-induced neurotoxicity. Here, we show that p75-deficient sympathetic neurons are more sensitive to A beta-induced neurite growth inhibition. To investigate the role of p75 in the sympathetic nervous system of AD, p75 mutant mice were crossed with a mouse line of AD model. The majority of p75-deficient AD mice died by 3 weeks of age. The lethality is associated with severe defects in sympathetic innervation to multiple organs. When 1 copy of the BACE1 gene encoding a protein essential in A beta production was deleted in p75-deficient AD mice, sympathetic innervation was significantly restored. These results suggest that p75 is neuroprotective for the sympathetic nervous system in a mouse model of AD.