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Proc Natl Acad Sci U S A. 1994 Oct 25; 91(22): 10703–10706.

Expression of the low-affinity nerve growth factor receptor enhances beta-amyloid peptide toxicity.


The low-affinity nerve growth factor receptor (NGFR) p75NGFR induces apoptosis in the absence of nerve growth factor (NGF) binding but enhances neural survival when bound by NGF. Basal forebrain cholinergic neurons express the highest levels of p75NGFR in the adult human brain and are preferentially involved in Alzheimer disease, raising the question of whether there may be a functional relationship between the expression of p75NGFR and basal forebrain cholinergic neuronal degeneration in Alzheimer disease. The expression of p75NGFR by wild-type and mutant PC12 cells potentiated cell death induced by beta-amyloid peptide. NGF binding to p75NGFR inhibited the toxicity of beta-amyloid peptide, whereas NGF binding to TrkA, the high-affinity NGFR, enhanced it. These results suggest a possible link between beta-amyloid peptide toxicity and preferential degeneration of cells expressing p75NGFR.

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  • Brun A, Gustafson L. Distribution of cerebral degeneration in Alzheimer's disease. A clinico-pathological study. Arch Psychiatr Nervenkr (1970) 1976 Dec 31;223(1):15–33. [PubMed]
  • Davies P, Maloney AJ. Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet. 1976 Dec 25;2(8000):1403–1403. [PubMed]
  • Bowen DM, Davison AN. Biochemical studies of nerve cells and energy metabolism in Alzheimer's disease. Br Med Bull. 1986 Jan;42(1):75–80. [PubMed]
  • Francis PT, Palmer AM, Sims NR, Bowen DM, Davison AN, Esiri MM, Neary D, Snowden JS, Wilcock GK. Neurochemical studies of early-onset Alzheimer's disease. Possible influence on treatment. N Engl J Med. 1985 Jul 4;313(1):7–11. [PubMed]
  • Bigl V, Woolf NJ, Butcher LL. Cholinergic projections from the basal forebrain to frontal, parietal, temporal, occipital, and cingulate cortices: a combined fluorescent tracer and acetylcholinesterase analysis. Brain Res Bull. 1982 Jun;8(6):727–749. [PubMed]
  • Woolf NJ, Hernit MC, Butcher LL. Cholinergic and non-cholinergic projections from the rat basal forebrain revealed by combined choline acetyltransferase and Phaseolus vulgaris leucoagglutinin immunohistochemistry. Neurosci Lett. 1986 May 23;66(3):281–286. [PubMed]
  • Butcher LL, Semba K. Reassessing the cholinergic basal forebrain: nomenclature schemata and concepts. Trends Neurosci. 1989 Dec;12(12):483–485. [PubMed]
  • Averback P. Lesions of the nucleus ansae peduncularis in neuropsychiatric disease. Arch Neurol. 1981 Apr;38(4):230–235. [PubMed]
  • Cummings JL, Benson DF. The role of the nucleus basalis of Meynert in dementia: review and reconsideration. Alzheimer Dis Assoc Disord. 1987;1(3):128–155. [PubMed]
  • Yankner BA, Duffy LK, Kirschner DA. Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides. Science. 1990 Oct 12;250(4978):279–282. [PubMed]
  • Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L, et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature. 1991 Feb 21;349(6311):704–706. [PubMed]
  • Arendt T, Taubert G, Bigl V, Arendt A. Amyloid deposition in the nucleus basalis of Meynert complex: a topographic marker for degenerating cell clusters in Alzheimer's disease. Acta Neuropathol. 1988;75(3):226–232. [PubMed]
  • Woolf NJ, Jacobs RW, Butcher LL. The pontomesencephalotegmental cholinergic system does not degenerate in Alzheimer's disease. Neurosci Lett. 1989 Jan 30;96(3):277–282. [PubMed]
  • Woolf NJ, Gould E, Butcher LL. Nerve growth factor receptor is associated with cholinergic neurons of the basal forebrain but not the pontomesencephalon. Neuroscience. 1989;30(1):143–152. [PubMed]
  • Rabizadeh S, Oh J, Zhong LT, Yang J, Bitler CM, Butcher LL, Bredesen DE. Induction of apoptosis by the low-affinity NGF receptor. Science. 1993 Jul 16;261(5119):345–348. [PubMed]
  • Liu YJ, Joshua DE, Williams GT, Smith CA, Gordon J, MacLennan IC. Mechanism of antigen-driven selection in germinal centres. Nature. 1989 Dec 21;342(6252):929–931. [PubMed]
  • Mah SP, Zhong LT, Liu Y, Roghani A, Edwards RH, Bredesen DE. The protooncogene bcl-2 inhibits apoptosis in PC12 cells. J Neurochem. 1993 Mar;60(3):1183–1186. [PubMed]
  • Behl C, Davis J, Cole GM, Schubert D. Vitamin E protects nerve cells from amyloid beta protein toxicity. Biochem Biophys Res Commun. 1992 Jul 31;186(2):944–950. [PubMed]
  • Ibáez CF, Ebendal T, Barbany G, Murray-Rust J, Blundell TL, Persson H. Disruption of the low affinity receptor-binding site in NGF allows neuronal survival and differentiation by binding to the trk gene product. Cell. 1992 Apr 17;69(2):329–341. [PubMed]
  • Yankner BA, Caceres A, Duffy LK. Nerve growth factor potentiates the neurotoxicity of beta amyloid. Proc Natl Acad Sci U S A. 1990 Nov;87(22):9020–9023. [PMC free article] [PubMed]
  • Meinecke DL, Rakic P. Low-affinity p75 nerve growth factor receptor expression in the embryonic monkey telencephalon: timing and localization in diverse cellular elements. Neuroscience. 1993 May;54(1):105–116. [PubMed]
  • Mufson EJ, Kordower JH. Cortical neurons express nerve growth factor receptors in advanced age and Alzheimer disease. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):569–573. [PMC free article] [PubMed]
  • Mufson EJ, Higgins GA, Kordower JH. Nerve growth factor receptor immunoreactivity in the new world monkey (Cebus apella) and human cerebellum. J Comp Neurol. 1991 Jun 22;308(4):555–575. [PubMed]
  • Joachim CL, Morris JH, Selkoe DJ. Diffuse senile plaques occur commonly in the cerebellum in Alzheimer's disease. Am J Pathol. 1989 Aug;135(2):309–319. [PMC free article] [PubMed]

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