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Nerve Growth Factor Systems in Alzheimer’s Disease

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Cerebral Cortex

Part of the book series: Cerebral Cortex ((CECO,volume 14))

Abstract

In many neurological disorders, specific neuronal populations are selectively vulnerable. This is especially true for patients with Alzheimer’s disease (AD). A consistent and early pathological feature of AD is the degeneration of cholinergic basal forebrain neurons (CBF) (Bartus et al., 1982; Whitehouse et al., 1983; Mufson et al., 1989a), a cell population that projects widely to the entire cortical mantle (Mesulam et al., 1983). Although there are numerous neuropathological and neurochemical deficits in the AD brain, cortical cholinergic dysfunction resulting from atrophy and degeneration of cholinergic basal forebrain (CBF) neurons is the pathologic feature that correlates best with the cognitive impairment (Bierer et al., 1995). During the last fifteen years it has become increasingly clear that neurotrophic molecules play a key role in the survival and maintenance of some adult neuronal populations, including the cholinergic neurons of the basal forebrain (see Hefti et al., 1989, for review). The viability and phenotypic expression of CBF neurons are potently modified by nerve growth factor (NGF), the prototype neurotrophic molecule first characterized by Levi-Montalcini and coworkers (see Levi-Montalcini and Angelleti, 1968; Thoenen and Barde, 1980). Nerve growth factor is just one member of a superfamily of neurotrophic factors that includes brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), neutotrophin-5 (NT-5), and neurotrophin-6 (NT-6) (Maisonpierre et al., 1990; Bothwell, 1991; Ibanez et al., 1992; Ip et al., 1992; Jing et al., 1992; Barbacid, 1994; Koster et al., 1994).

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References

  • Appel, S. H., 1981, A unifying hypothesis for the cause of amyotrophic lateral sclerosis, Parkinsonism, and Alzheimer’s disease, Ann. Neurol. 10:499–505.

    Article  PubMed  CAS  Google Scholar 

  • Armstrong, D. M., Terry, R. D., Deteresa, R. M., Bruce, G., Hersh, L. B., and Gage, F. H., 1987, Response of septal cholinergic neurons to axotomy, J. Comp. Neurol. 264:421–436.

    Article  PubMed  CAS  Google Scholar 

  • Backman, C., Biddle, P. T., Ebendal, T., Friden, P. M., Gerhardt, G. A., Henry, M. A., Mackerlova, L., Soderstrom, S., Stromberg, I., Walus, L., and Granholm, A.-C., 1995, Effects of transferrin receptor antibody-NGF conjugate on young and aged septal transplants in oculo, Exp. Neurol. 132:1–15

    Article  PubMed  CAS  Google Scholar 

  • Barbacid, M., 1994, The trk family of neurotrophin receptors, J. Neurobiol. 25:1386–1403.

    Article  PubMed  CAS  Google Scholar 

  • Bartus, R. T., Dean, R. L., Beer, B., and Lippa, A. S., 1982, The cholinergic hypothesis of geriatric memory dysfunction, Science 217:408–417.

    Article  PubMed  CAS  Google Scholar 

  • Bartus, R. T., Dean, R. L., Abelleira, S., Charles, V., and Kordower, J. H., 1996, Dissociation of p75 receptors and nerve growth factor neurotrophic effects: Lack of p75 immunoreactivity in striatum following physical trauma, excitotoxicity, and NGF administration, Restar. Neurol. 10:49–59.

    CAS  Google Scholar 

  • Batchelor, P. E., Armstrong, D. M., Blaker, S. N., and Gage, F. H., 1989, Nerve growth factor receptor and choline acetyltransferase colocalization in neurons within the rat forebrain: Response to fimbria-fornix transection, J. Comp. Neurol. 284:187–204.

    Article  PubMed  CAS  Google Scholar 

  • Benzing, W. C., Kordower, J. H., and Mufson, E.J., 1993, Galanin immunoreactivity within the primate basal forebrain: Evolutionary change between monkeys and apes, J. Comp. Neurol. 283:189–194.

    Google Scholar 

  • Biegon, A., Greenberger, V., and Segal, M., 1986, Quantitative histochemistry of brain acetylcholine and learning rate in the aged rat, Neurobiol. Aging 7:215–217.

    Article  PubMed  CAS  Google Scholar 

  • Bierer, L. M., Haroutunian, V., Gabreil, S., Knott, P. J., Carlin, L. S., Purohit, D. P., Perl, D. P., Schmeidler, J., Kanof, P., and Davis, K. L., 1995, Neurochemical correlates of dementia in Alzheimer’s disease: Relative importance of cholinergic deficits, J. Neurochem. 64:749–760.

    Article  PubMed  CAS  Google Scholar 

  • Boissière, B., Faucheux, Y., Agid, Y., and Hirsch, E. C., 1996, Decrease of trkA mRNA level in cholinergic neurons of the striatum and basal forebrain in Alzheimer’s disease, Soc. Neurosci. Abstr. 22:210.

    Google Scholar 

  • Bothwell, M., 1991, Keeping track of neurotrophin receptors, Cell 65:915–918.

    Article  PubMed  CAS  Google Scholar 

  • Bowser, R., Kordower, J. H., and Mufson, E. J. (1997), A confocal microscopic analysis of galaninergic hyperinnervation of cholinergic basal forebrain neurons in Alzheimer’s disease, Brain Pathol. 7:723–730.

    Article  PubMed  CAS  Google Scholar 

  • Chan-Palay, V., 1988, Galanin hyperinnervates surviving neurons of the human basal nucleus of Meynert in dementias of Alzheimer’s and Parkinson’s disease: A hypothesis for the role of galanin in accentuating cholinergic dysfunction in dementia, J. Comp. Neurol. 273:543–557.

    Article  PubMed  CAS  Google Scholar 

  • Chao, M. V., 1992, Neurotrophin receptors: A window into neuronal differentiation, Neuron 9:583–593.

    Article  PubMed  CAS  Google Scholar 

  • Chao, M. V., 1995, The p75 neurotrophin receptor, J. Neurobiol. 25:1375–1385.

    Google Scholar 

  • Chao, M. V., and Hempstead, B. L., 1995, p75 and Trk: A two-receptor system, Trends Neurosci. 18:321–326.

    Article  PubMed  CAS  Google Scholar 

  • Charles, V., Mufson, E. J., Friden, P. M., Bartus, R. T., and Kordower, J. H., 1996, Atrophy of cholinergic basal forebrain neurons following excitotoxic cortical lesions is reversed by intravenous administration of an NGF conjugate, Brain Res. 728:193–203.

    Article  PubMed  CAS  Google Scholar 

  • Chen, E.-Y., Mufson, E. J., and Kordower, J. H., 1996, Trk and p75 NGF receptor systems in the developing human brain, J. Comp. Neurol. 369:591–618.

    Article  PubMed  CAS  Google Scholar 

  • Collier, T. J., and Coleman, P., 1991, Divergence of biological and chronological aging: Evidence from rodent studies, Neurobiol. Aging 12:685–693.

    Article  PubMed  CAS  Google Scholar 

  • Conner, J. M., and Varon, S., 1992, Distribution of nerve growth factor-like immunoreactive neurons in the adult rat brain following colchicine treatment, J. Comp. Neurol. 326:347–362.

    Article  PubMed  CAS  Google Scholar 

  • Conner, J. M., Muir, D., Varon, S., Hagg, T., and Manthorpe, M., 1992, The localization of nerve growth factor-like immunoreactivity in the adult rat basal forebrain and hippocampal formation, J. Comp. Neurol. 319:454–462.

    Article  PubMed  CAS  Google Scholar 

  • Cooper, J. D., Lindholm, D., and Sofroniew, M. V., 1994, Reduced transport of [125I] nerve growth factor by cholinergic neurons and down-regulated TrkA expression in the medial septum of aged rats, Neurosci. 62:625–639.

    Article  CAS  Google Scholar 

  • Crawley, J. N., 1996, Galanin-acetylcholine interactions: Relevance to memory and Alzheimer’s disease, Life Sci. 58:2185–2199.

    Article  PubMed  CAS  Google Scholar 

  • Crutcher, K. A., Scott, S. A., Liang, S., Everson, W. V., and Weingartner, J., 1993, Detection of NGF-like activity in the human brain tissue: Increased levels in Alzheimer’s disease, J. Neurosci. 13:2540–2550.

    PubMed  CAS  Google Scholar 

  • de Lacalle, S., Lim, C., Sobreviela, T., Mufson, E. J., Hersh, L. B., and Saper, C. B., 1994, Cholinergic innervation in the human hippocampal formation including the entorhinal cortex, J. Comp. Neurol. 345:321–344.

    Article  PubMed  Google Scholar 

  • Emerich, D. F., Winn, S. R., Hammang, J. P., Baetge, E. E., and Kordower, J. H., 1994, Grafts of polymer-encapsulated cells genetically modified to secrete nerve growth factor rescue basal forebrain neurons in nonhuman primates, J. Comp. Neurol. 349:148–165.

    Article  PubMed  CAS  Google Scholar 

  • Ernfors, P., Lindefors, N., Chan-Palay, V., and Persson, H., 1990, Cholinergic neurons of the nucleus basalis express elevated levels of nerve growth factor receptor mRNA in senile dementia of the Alzheimer’s type, Dementia 1:138–145.

    Google Scholar 

  • Feinstein, D., and Larhammar, D., 1990, Identification of a conserved protein motif in a group of growth factor receptors, FEBS Lett. 272:7–11.

    Article  PubMed  CAS  Google Scholar 

  • Figueiredo, B. C., Skup, M., Bedard, A. M., Tetzlaff, W., and Cuello, A. C., 1995, Differential expression of p140trk, p75NGFr, and growth-associated phosphoprotein-43 genes in nucleus basalis magnocellularis, thalamus, and adjacent cortex following neocortical infarction and nerve growth factor treatment, Neuroscience 68:29–45.

    Article  PubMed  CAS  Google Scholar 

  • Fischer, W., Wictorin, K., Bjorklund, A., Williams, L. R., Varon, S., and Gage, F. H., 1987, Amelioration of cholinergic neuron atrophy and spatial memory impairment in aged rats by nerve growth factor, Nature 329:65–68.

    Article  PubMed  CAS  Google Scholar 

  • Fisone, G., Wu, C. F., Consolo, S., Nordstrom, O., Brynne, N., Bartfai, T., Melander, T., and Hokfelt, T., 1987, Galanin inhibits acetylcholine release in the ventral hippocampus of the rat: Histochemical, autoradiographic, in vivo, and in vitro studies, Proc. Natl. Acad. Sci. USA 84:7339–7343.

    Article  PubMed  CAS  Google Scholar 

  • Friden, P. M., Walus, L. R., Musso, G. F., Taylor, M. A., Malfroy, B., and Starzyk, R. M., 1991, Antitransferrin receptor antibody and antibody-drug conjugates cross the blood-brain barrier, Proc. Natl. Acad. Sci. USA 88:4771–4775.

    Article  PubMed  CAS  Google Scholar 

  • Friden, P. M., Walus, L. R., Watson, P., Doctrow, S. R., Kozarich, J. W., Backman, C., Bergman, H., Hoffer, B., Bloom, F., and Granholm, A. C., 1993, Blood-brain barrier penetration and in vivo activity of an NGF conjugate, Science 259:373–377.

    Article  PubMed  CAS  Google Scholar 

  • Gage, F. H., Batchelor, P., Chen, K. S., Chin, D., Higgins, G. A., Koh, S., Deputy, S., Rosenberg, M. B., Fischer, W., and Bjorklund, A., 1989, NGF receptor reexpression and NGF-mediated cholinergic neuronal hypertrophy in the damaged adult neostriatum, Neuron 2:1177–1184.

    Article  PubMed  CAS  Google Scholar 

  • Geddes, J. W., Mongahan, D. T., Cotman, C. W., Lott, I. T., Kim, R. C., and Chui, H.-C., 1985, Plasticity of hippocampal circuitry in Alzheimer’s disease, Science 230:1179–1181.

    Article  PubMed  CAS  Google Scholar 

  • Gibbs, R. B., and Pfaff, D. W., 1994, In situ hybridization detection of trkA mRNA in brain: Distribution, colocalization with p75NGFR, and up-regulation by nerve growth factor, J. Comp. Neurol. 341:324–339.

    Article  PubMed  CAS  Google Scholar 

  • Gnahn, H., Hefti, F., Heumann, R., Schwab, M. E., and Thoenen, H., 1983, NGF mediated increase of choline acetyltransferase (ChAT) in the neonatal forebrain: Evidence for a physiological role of NGF in the brain? Dev. Brain Res. 9:45–52.

    Article  CAS  Google Scholar 

  • Goedert, M., Fine, A., Hunt, S. P., and Ulrich, A., 1986, NGF RNA in peripheral and rat central tissues and in the human central nervous system: Lesion effects in the rat brain and levels in Alzheimer’s disease, Mol. Brain Res. 1:85–92.

    Article  Google Scholar 

  • Granholm, A.-C., Biddle, P. T., Backman, C., Ebenberg, T., Gerhardt, G., Hoffer, B., Mackerlova, L., Olson, L., Soderstrom, S., Walus, L., and Friden, P., 1994, Peripheral administration of nerve growth factor conjugated to an anti-transferrin receptor antibody increase cholinergic neuron survival in intraocular forebrain transplants, in: Providing Pharmacological Access to the Brain: Alternative Approaches (T. R. Flanagan, D. W. Emerich, and S. R. Winn, eds.), Academic, New York, pp. 71–92.

    Google Scholar 

  • Granholm, A. C., Backman, C., Bloom, F., Ebendal, T., Gerhardt, G. A., Hoffer, B., Mackerlova, L., Olson, L., Soderstrom, S., Walus, L. R., and Friden, P. M., 1993, NGF and anti-transferrin receptor antibody conjugate: Short and long-term effects on survival of cholinergic neurons in intraocular septal transplants, J. Pharmacol. Exp. Ther. 268:448–459.

    Google Scholar 

  • Hefti, F., and Weiner, W. J., 1983, Is Alzheimer’s disease caused by lack of nerve growth factor? Ann. Neurol. 13:109–110.

    Article  PubMed  CAS  Google Scholar 

  • Hefti, F., and Mash, D. C., 1989, Localization of nerve growth factor receptors in the normal human brain and in Alzheimer’s disease, Neurobiol. Aging 10:75–87.

    Article  PubMed  CAS  Google Scholar 

  • Hefti, F., Hartikka, J., Eckenstein, F., Gnahn, H., Heumann, R., and Schwab, M., 1985, Nerve growth factor (NFG) increases choline acetyltransferase, but not survival or fiber outgrowth, of cultured fetal septal cholinergic neurons, Neuroscience 14:55–68.

    Article  PubMed  CAS  Google Scholar 

  • Hefti, F., Hartikka, J., Salviaterra, P., Weiner, W. J., and Mash, D. C., 1986, Localization of nerve growth factor receptors on cholinergic neurons of the human basal forebrain, Neurosci. Lett. 69:275–281.

    Article  Google Scholar 

  • Hefti, F., Hartikka, J., and Knusel, B., 1989, Function of neurotrophic factors in the adult and aging brain and their possible use in the treatment of neurodegenerative disease, Neurobiol. Aging 10:515–533.

    Article  PubMed  CAS  Google Scholar 

  • Heldin, C.-H., 1995, Dimerization of cell surface receptors in signal transduction, Cell 80:213–223.

    Article  PubMed  CAS  Google Scholar 

  • Hempstead, B. L., Martin-Zanca, D., Kaplan, D. R., Parada, L. R., and Chao, M. V., 1991, High-affinity NFF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor, Nature 350:678–683.

    Article  PubMed  CAS  Google Scholar 

  • Heumann, R., Schwab, M., Merkl, R., and Thoenen, H., 1984, Nerve growth factor-mediated induction of choline acetyl transferase in PC12 cells: Evaluation of the site of action of nerve growth factor and the involvement of lysosomal degradation products of nerve growth factor, J. Neurosci. 4:3030–3050.

    Google Scholar 

  • Higgins, G. A., and Mufson, E. J., 1989, NGF receptor gene expression is decreased in the nucleus basalis in Alzheimer’s disease, Exp. Neurol. 106:222–236.

    Article  PubMed  CAS  Google Scholar 

  • Holtzman, D. M., Kilbridge, J., Li, Y., Cunningham, E. T., Jr., Lenn, N. J., Clary, D. O., Reichardt, L. F., and Mobley, W. C., 1995, TrkA expression in the CNS: Evidence for the existence of several novel NGF-responsive CNS neurons, J. Neurosci. 15:1567–1676.

    PubMed  CAS  Google Scholar 

  • Ibanez, C. F., Ebendal, T., Barbany, G., Murray-Rust, J., Blundell, T. L., and Persson, H., 1992, Similarities and differences in the way neurotrophins interact with the trk receptors in neuronal and nonneuronal cells, Cell 69:329–341.

    Article  PubMed  CAS  Google Scholar 

  • Ip, N., Ibanez, C., Nye, S., McClain, J., Jones, P. F., Gies, D. R., Belluscio, L., Le Beau, M. M., Espinsosa, R., III, Squinto, S. P., Persson, H., and Yancopoulos, G. D., 1992, Mammalian neurotrophin-4: Structure, chromosomal localization, tissue distribution, and receptor specificity, Proc. Natl. Acad. Sci. USA 89:3060–3064.

    Article  PubMed  CAS  Google Scholar 

  • Ip, N., Tapley, P., Glass, D. J., Greene, L. A., and Yancopoulos, G. D., 1993, Similarities and differences in the way neurotrophins interact with the trk receptors in neuronal and nonneuronal cells, Neuron 10:137–149.

    Article  PubMed  CAS  Google Scholar 

  • Jing, S., Tapley, P., and Barbacid, M., 1992, Nerve growth factor mediates signal transduction through trk homodimer receptors, Neuron 9:1067–1079.

    Article  PubMed  CAS  Google Scholar 

  • Kaplan, D. R., and Stephens, R. M., 1994, Neurotrophin signal transduction by the trk receptor, J. Neurobiol. 25:1404–1417.

    Article  PubMed  CAS  Google Scholar 

  • Kaplan, D. R., Hempstead, B. L., Martin-Zanca, D., Chao, M. V., and Parada, L. F., 1991, The trk protooncogene product: Signal transducting receptor for nerve growth factor, Science 252:554–558.

    Article  PubMed  CAS  Google Scholar 

  • Kawaja, M. D., Rosenberg, M. B., Yoshida, K., and Gage, F. H., 1992, Somatic gene transfer of nerve growth factor promotes the survival of axotomized septal neurons and the regenerations of the axons in adult rats, J. Neurosci. 12:2849–2864.

    PubMed  CAS  Google Scholar 

  • Koh, S., and Loy, R., 1988, Age-related loss of nerve growth factor sensitivity in rat basal forebrain neurons, Brain Res. 440:396–401.

    Article  PubMed  CAS  Google Scholar 

  • Koh, S., Chang, P., Collier, T. J., and Loy, R., 1989, Loss of NGF receptor immunoreactivity in basal forebrain neurons of aged rats: Correlation with spatial memory impairment, Brain Res. 498:397–404.

    Article  PubMed  CAS  Google Scholar 

  • Koliatsos, V. E., Price, D. L., Gouras, G. K., Cayouette, M. H., Burton, L. E., and Winslow, J. W., 1994, Highly selective effects of nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-e on intact and injured basal forebrain magnocellular neurons, J. Comp. Neurol. 343:247–262.

    Article  PubMed  CAS  Google Scholar 

  • Kordower, J. H., and Mufson, E. J., 1989, NGF and Alzheimer’s disease: Unfulfilled promise and untapped potential, Neurobiol. Aging 10:543–544.

    Article  PubMed  CAS  Google Scholar 

  • Kordower, J. H., and Mufson, E. J., 1990, Galanin-like immunoreactivity within the primate basal forebrain: Differential staining patterns between humans and monkeys, J. Comp. Neurol. 294:281–292.

    Article  PubMed  CAS  Google Scholar 

  • Kordower, J. H., and Mufson, E. J., 1992, NGF receptor immunoreactive neurons within the developing human cerebral cortex and hippocampal complex, J. Comp. Neurol. 323:25–41.

    Article  PubMed  CAS  Google Scholar 

  • Kordower, J. H., Bartus, R. T., Bothwell, M., Schatteman, G., and Gash, D. M., 1988, Nerve growth factor receptor immunoreactivity in the nonhuman primate (Cebus apella): Distribution, morphology, and colocalization with cholinergic enzymes, J. Comp. Neurol. 277:465–486.

    Article  PubMed  CAS  Google Scholar 

  • Kordower, J. H., Gash, D. M., Bothwell, M., Hersh, L. B., and Mufson, E. J., 1989, Nerve growth factor receptor and choline acetyltransferase remain colocalized in the nucleus basalis (Ch4) of Alzheimer’s patients, Neurobiol. Aging 10:287–294.

    Article  Google Scholar 

  • Kordower, J. H., Le, H. K., and Mufson, E. J., 1992, Galanin-immunoreactivity in the primate central nervous system, J. Comp. Neurol. 319:479–500.

    Article  PubMed  CAS  Google Scholar 

  • Kordower, J. H., Mufson, E. J., Granholm, A. C., Hoffer, B., and Friden, P. M., 1993, Delivery of trophic factors to the primate brain, Exp. Neurol. 124:21–30.

    Article  PubMed  CAS  Google Scholar 

  • Kordower, J. H., Chen, E.-Y., Sladek, J. R., Jr., and Mufson, E. J., 1994b. Trk-immunoreactivity in the monkey central nervous system. I. Forebrain, J. Comp. Neurol. 349:20–35.

    Article  PubMed  CAS  Google Scholar 

  • Kordower, J. H., Winn, S. R., Liu, Y-T., Mufson, E. J., Sladek, J. R., Hammang, J. P., Baetge, E. E., and Emerich, D. F., 1994c, The aged monkey basal forebrain: Rescue and sprouting of degenerating cholinergic neurons following grafts of polymer-encapsulated human NGF secreting cells, Proc. Natl. Acad. Sci. USA 91:10898–10902.

    Article  PubMed  CAS  Google Scholar 

  • Kordower, J. H., Charles, V., Bayer, R., Bartus, R. T., Putney, S., Walus, L., and Friden, P. M., 1994a, Intravenous administration of an NGF conjugate prevents neuronal degeneration in a model of Huntington’s disease, Proc. Natl. Acad. Sci. USA 91:9077–9080.

    Article  PubMed  CAS  Google Scholar 

  • Kordower, J. H., Mufson, E. J., Fox, N., Martel, L., and Emerich, D., 1997, NGF does not alter the expression of β amyloid-immunoreactivity in the young or aged nonhuman primate, Exp. Neurol. 145:586–591.

    Article  PubMed  CAS  Google Scholar 

  • Koster, G. R., Winkler, C., Raulf, F., Lottspeich, F., Schartl, M., and Thoenen, H., 1994, Neurotrophin-6 is a new member of the nerve growth family, Nature 372:266–269.

    Article  PubMed  Google Scholar 

  • Kromer, L. F., 1987, Nerve growth factor treatment after brain injury prevents neuronal death, Science 235:214–216.

    Article  PubMed  CAS  Google Scholar 

  • LeSauteur, L., Malirtchouk, S., Lejeune, H., Quirion, R., and Saragovi, H. U., 1996, Potent human p40-trk agonists derived from an anti-receptor monoclonal antibody, J. Neurosci. 16:1308–1316.

    PubMed  CAS  Google Scholar 

  • Levi-Montalcini, R., and Angeletti, P. U., 1968, Nerve growth factor, Physiol. Rev. 8:534–569.

    Google Scholar 

  • Lindsay, R. M., Wiegand, S. J., Altar, C. A., and Distephano, P. S., 1994, Neurotrophic factors: From molecule to man, Trends Neurosci. 17:182–190.

    Article  PubMed  CAS  Google Scholar 

  • Lucidi-Phillipi, C. A., Clary, D. O., Reichardt, L. F., and Gage, F., 1996, TrkA activation is sufficient to rescue axotomized cholinergic neurons, Neuron 16:653–663.

    Article  PubMed  CAS  Google Scholar 

  • Maisonpierre, P. C., Bellusco, L., Friedman, B., Alderson, R. F., 1990, NT-3, BDNF in the developing rat nervous system: Parallel as well as reciprocal patterns of expression, Neuron 4:501–509.

    Article  Google Scholar 

  • Martinez, H. J., Dryfuss, C. F., Jonakait, G. M., and Black, I. B., 1985, Nerve growth factor promotes cholinergic development in brain striatal cultures, Proc. Natl. Acad. Sci. USA 82:7777–7781.

    Article  PubMed  CAS  Google Scholar 

  • Markram, H., and Segal, M., 1990, Regional changes in NGF receptor immunohistochemical labeling in the septum of the aged rat, Neurobiol. Aging 11:481–484.

    Article  PubMed  CAS  Google Scholar 

  • Meakin, S. O., and Shooter, E. M., 1991, Molecular investigation of the high-affinity nerve growth factor receptor, Neuron 6:153–163.

    Article  PubMed  CAS  Google Scholar 

  • Melander, T., Hökfelt, T., and Rokaeus, A., 1986, Distribution of galanin-like immunoreactivity in the rat central nervous system, J. Comp. Neurol. 248:475–517.

    Article  PubMed  CAS  Google Scholar 

  • Mesulam, M. M., Mufson, E. J., Levey, A. I., and Wainer, B. H., 1983, Cholinergic innervation of cortex by the basal forebrain: Cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey, J. Comp. Neurol. 214:170–197.

    Article  PubMed  CAS  Google Scholar 

  • Mobley, W. C., Tennekoon, J. L., Buchannan, K., and Johnston, M. V., 1985, Choline acetyltransferase activity in the striatum of neonatal rats is increased by nerve growth factor, Science 229:284–287.

    Article  PubMed  CAS  Google Scholar 

  • Mufson, E. J., and Kordower, J. H., 1992, Cortical neurons express the receptor for NGF in advanced age and Alzheimer’s disease, Proc. Natl. Acad. Sci. USA 89:569–573.

    Article  PubMed  CAS  Google Scholar 

  • Mufson, E. J., Bothwell, M., and Kordower, J. H., 1989b, Loss of nerve growth factor receptor-containing neurons in Alzheimer’s disease: A quantitative analysis across subregions of the basal forebrain, Exp. Neurol. 105:221–232.

    Article  PubMed  CAS  Google Scholar 

  • Mufson, E. J., Bothwell, M., Hersh, L. B., and Kordower, J. H., 1989a, Nerve growth factor receptor immunoreactive profiles in the normal aged human basal forebrain: Colocalization with cholinergic neurons, J. Comp. Neurol. 285:196–217.

    Article  PubMed  CAS  Google Scholar 

  • Mufson, E.J., Cochran, E., Benzing, W. C., and Kordower, J. H., 1993, Galaninergic innervation of the cholinergic vertical limb of the diagonal band (Ch2) and bed nucleus of the striia terminalis in aging, Alzheimer’s disease, and Down’s syndrome, Dementia 4:237–250.

    PubMed  CAS  Google Scholar 

  • Mufson, E. J., Connor, J., Varon, S., and Kordower, J. H., 1994, Nerve growth factor immunoreactivity in the basal forebrain and hippocampus in primates and Alzheimer’s disease, J. Comp. Neurol. 341:507–519.

    Article  PubMed  CAS  Google Scholar 

  • Mufson, E. J., Connor, J. M., and Kordower, J. H., 1995, NGF and Alzheimer’s disease: Defective retrograde transport to the nucleus basalis, NeuroReport 6:1063–1066.

    Article  PubMed  CAS  Google Scholar 

  • Mufson, E. J., Li, J.-M., Sobreviela, T., and Kordower, J. H., 1996, Decreased trkA gene expression within basal forebrain neurons in Alzheimer’s disease, NeuroReport 7:25–29, 1996.

    Article  Google Scholar 

  • Mufson, E. J., Lavine, N., Jaffar, S., Kordower, J. H., Quirion, R., and Saragovi, H. U., 1997, Reduction in p140-TrkA receptor protein within the nucleus basalis and cortex in Alzheimer’s disease, Exp. Neurol. 146:91–103.

    Article  PubMed  CAS  Google Scholar 

  • Olson, L., 1993, NGF and the treatment of Alzheimer’s disease, Exp. Neurol. 124:5–15.

    Article  PubMed  CAS  Google Scholar 

  • Parada, L. F., Tsoulfas, P., Tessarollo, L., Blair, J., Reid, S. W., and Soppert, D., 1992, The trk family of tyrosine kinases-receptors for NGF-related neurotrophins, Cold Spring Harbor Symp. Quant. Biol. 57:43–51.

    Article  PubMed  CAS  Google Scholar 

  • Perry, E. K., 1980, The cholinergic system in old age and Alzheimer’s disease, Age Ageing 9:1–8.

    Article  PubMed  CAS  Google Scholar 

  • Planas, B., Kolb, P. E., Ruskind, M. A., and Miller, M. A., 1997, Nerve growth factor induces galanin gene expression in the rat basal forebrain: implications for treatment of cholinergic dysfunction, J. Comp. Neurol. 379:563–570.

    Article  PubMed  CAS  Google Scholar 

  • Richardson, P. M,. Verge Issa, V. M. K., and Riopelle, R. J., 1986, Distribution of neuronal receptor for nerve growth factor in the rat, J. Neurosci. 6:2312–2321.

    PubMed  CAS  Google Scholar 

  • Rodriguez-Tebar, A., Dechant, G., and Barde, Y.-A., 1990, Binding of brain-derived neurotrophic factor to the nerve growth factor receptor, Neuron 4:487–492.

    Article  PubMed  CAS  Google Scholar 

  • Salehi, A., Verhaggen, J., Dijhuizen, P. A., and Swaab, D. F., 1996, Colocalization of high affinity neuro-trophin receptors in nucleus basalis of Meynert neurons and their differential reduction in Alzheimer’s disease, Neuroscience 75:373–387.

    Article  PubMed  CAS  Google Scholar 

  • Saporito, M. S., Carswell, S., 1995, High levels of synthesis and local effects of nerve growth factor in the septal region of the adult rat brain, J. Neurosci. 15:2280–2286.

    PubMed  CAS  Google Scholar 

  • Schumacher, J. M., Short, M. P., Hyman, B. T., Breakefield, X. O., and Isacson, O., 1991, Intracerebral implantation of nerve growth factor-producing fibroblasts protects striatum against neurotoxic levels of excitatory amino acids, Neuroscience 45:561–570.

    Article  PubMed  CAS  Google Scholar 

  • Schwaab, M. E., Otten, U., Agid, Y., and Thoenen, H., 1979, Nerve growth factor in the rat CNS: Absence of specific retrograde transport and tyrosine hydroxylase induction in the locus coeruleus and substantia nigra, Brain Res. 168:473–483.

    Article  Google Scholar 

  • Scott, S. A., and Crutcher, K. A., 1994, Nerve growth factor and Alzheimer’s disease, Rev. Neurosci. 5:179–211.

    PubMed  CAS  Google Scholar 

  • Scott, S. A., Weingartner, J. A., Liang, S., and Crutcher, K. A., 1994, Increased NGF-like activity in young but not aged rat hippocampus after septal lesions, Neurobiol. Aging 15:337–346.

    Article  PubMed  CAS  Google Scholar 

  • Seiler, M., and Schwaab, M. E., 1984, Specific retrograde transport of nerve growth factor from neocortex to nucleus basalis in rat, Brain Res. 300:33–39.

    Article  PubMed  CAS  Google Scholar 

  • Shelton, D. L., Sutherland, J., Gripp, J., Camerato, T., Armanini, M., Philips, H., Carroll, K., Spencer, S. D., and Levinson, A. D., 1995, Human trks-molecular cloning, tissue distribution, and expression of extracellular domain immunoadhesions, J. Neurosci. 15:477–491.

    PubMed  CAS  Google Scholar 

  • Sobreviela, T., Clary, D. O., Reichardt, L. F., Brandabur, M. M., Kordower, J. H., and Mufson, E. J., 1995, TrkA immunoreactive profiles in the central nervous system: Colocalization with neurons containing p75 nerve growth factor receptor, choline acetyltransferase, and serotonin, J. Comp. Neurol. 350:587–611.

    Article  Google Scholar 

  • Sofroniew, M. V., Pearson, R. C. A., Eckenstein, F., Cuello, A. C., and Powell, T. P. S., 1983, Retrograde changes in cholinergic neurons in the basal forebrain of the rat following cortical damage, Brain Res. 289:370–374.

    Article  PubMed  CAS  Google Scholar 

  • Sofroniew, M. V., Pearson, R. C. A., and Powell, T. P. S., 1987, The cholinergic nuclei of the basal forebrain of the rat: Normal structure, development, and experimentally induced degeneration, Brain Res. 371:310–331.

    Article  Google Scholar 

  • Soltoff, S. P., Rabin, S. L., Cnatley, L. C., and Kaplan, D. R., 1992, Nerve growth factor promotes the activation of phosphatidylinositol-3 kinase and its association with the trk tyrosine-kinase, J. Biol. Chem. 267:17472–17477.

    PubMed  CAS  Google Scholar 

  • Springer, J. E., Koh, S. H., Tayrien, M. W., and Loy, R., 1987, Basal forebrain magnocellular neurons stain for nerve growth factor receptor: Correlation with cholinergic cell bodies and effects of axotomy, J. Neurosci. Res. 17:111–118.

    Article  PubMed  CAS  Google Scholar 

  • Steininger, T. L., Wainer, B. H., Klein, R., Barbicid, M., and Palfrey, H. C., 1993, High affinity nerve growth factor receptor (trk) immunoreactivity is localized in cholinergic neurons of the basal forebrain and striatum in the adult rat brain, Brain Res. 612:330–335.

    Article  PubMed  CAS  Google Scholar 

  • Strömberg, L., Wetmore, C. J., Ebendal, T., Ernfors, P., Persson, H., and Olson, L., 1990, Rescue of basal forebrain cholinergic neurons after implantation of genetically modified cells producing recombinant NGF, J. Neurosci. Res. 25:405–411.

    Article  PubMed  Google Scholar 

  • Thoenen, H., and Barde, Y A., 1980, Physiology of nerve growth factor, Physiol. Rev. 60:1284–1335.

    PubMed  CAS  Google Scholar 

  • Vogels, O. J., Broere, C. A. J., Ter Laak, H. J., ten Donkelaar, H. J., Nieuwenhuys, R., and Schulte, B. P. M., 1990, Cell loss and shrinkage in the nucleus basalis Meynert complex in Alzheimer’s disease, Neurobiol. Aging 11:3–13.

    Article  PubMed  CAS  Google Scholar 

  • Weskamp, G., and Reichardt, L. F., 1991, Evidence that biological activity of NGF is mediated through a novel subclass of high affinity receptors, Neuron 6:649–663.

    Article  PubMed  CAS  Google Scholar 

  • Whitehouse, P. J., Price, D. L., Struble, R. G., Clark, A. W., Coyle, J. T., and DeLong, M. R., 1983, Alzheimer’s disease and senile dementia: Loss of neurons in the basal forebrain, Science 215:1237–1239.

    Article  Google Scholar 

  • Whittemore, S. R., and Seiger, A., 1987, The expression, localization, and functional significance of B-nerve growth factor in the central nervous system, Brain Res. Rev. 12:439–464.

    Article  CAS  Google Scholar 

  • Will, L. R., and Hefti, F., 1985, Behavioral and neurochemical effects of chronic intraventricular injections of nerve growth factor in adult rats with fimbrial lesions, Behau Brain Res. 17:17–24.

    Article  CAS  Google Scholar 

  • Williams, L. R., Varon, S., Peterson, G. M., Wictorian, K., Fisher, W., Björklund, A., and Gage, F. H., 1986, Continuous infusion of nerve growth factor prevents basal forebrain neuronal cell death after fimbria-fornix transection, Proc. Natl. Acad. Sci. USA 83:9231–9236.

    Article  PubMed  CAS  Google Scholar 

  • Winn, S. R., Linder, M. D., Lee, A., Haggett, G., Francis, J. M., and Emerich, D. F., 1996, Polymer-encapsulated genetically modified cells continue to secrete human nerve growth factor for over one year in rat ventricles: Behavioral and anatomical consequences, Exp. Neurol. 140:126–138.

    Article  PubMed  CAS  Google Scholar 

  • Yan, Q., and Johnson, E. M., Jr., 1988, An immunohistochemical study of the nerve growth factor receptor in developing rats, J. Neurosci. 8:3481–3498.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Research Center for Brain Repair, Department of Neurological Sciences, Rush Alzheimer’s Disease Center, Rush Presbyterian-St. Luke’s Medical Center, Chicago, Illinois, 60612, USA

    E. J. Mufson & J. H. Kordower

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  1. E. J. Mufson
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  2. J. H. Kordower
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  1. Boston University School of Medicine, Boston, Massachusetts, USA

    Alan Peters

  2. Mount Sinai Medical Center, New York, New York, USA

    John H. Morrison

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Mufson, E.J., Kordower, J.H. (1999). Nerve Growth Factor Systems in Alzheimer’s Disease. In: Peters, A., Morrison, J.H. (eds) Cerebral Cortex. Cerebral Cortex, vol 14. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4885-0_19

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