p75 reduces beta-amyloid-induced sympathetic innervation deficits in an Alzheimer's disease mouse model.
Beta-amyloid (Abeta) 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 Abeta-induced neurotoxicity. Here, we show that p75-deficient sympathetic neurons are more sensitive to Abeta-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 Abeta 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.
Peptide Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Tasha G
TG
Bengoechea
Zhijiang
Z
Chen
Debra A
DA
O'Leary
Deborah
D
O'Leary
Eliezer
E
Masliah
Kuo-Fen
KF
Lee
D000544:Alzheimer Disease / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor / Q000502:physiology*; D013233:Stellate Ganglion / Q000378:metabolism; D013546:Sweating; D013564:Sympathetic Nervous System / Q000378:metabolism*; D013997:Time Factors
D016229:Amyloid beta-Peptides; D020800:Receptor, Nerve Growth Factor; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse