The amyloid protein precursor of Alzheimer's disease is a mediator of the effects of nerve growth factor on neurite outgrowth.
The beta A4 protein, the major component of the amyloid deposition characterizing Alzheimer's disease, derives from the amyloid protein precursor (APP), an integral membrane protein with soluble derivatives. The function of APP is unknown. Both soluble and membrane-associated human brain APP (10(-10) M) significantly increased (P less than 0.025) neurite length and branching in pheochromocytoma PC12 cells, but did not affect the number of neurites per cell. At higher concentrations, APP was cytotoxic, with a half-maximal concentration of 5 x 10(-9) M. Nerve growth factor (NGF) is known to affect APP expression in vivo and in vitro. Antibodies to APP specifically diminished the effects of NGF on neurite length and branching. Thus APP may act to mediate neurite outgrowth promotion by NGF.
Milward
E A
EA
Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
Papadopoulos
R
R
Fuller
S J
SJ
Moir
R D
RD
Small
D
D
Beyreuther
K
K
Masters
C L
CL
D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D016923:Cell Death / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats
D016564:Amyloid beta-Protein Precursor; D009414:Nerve Growth Factors