Shift in the Balance of TRKA and ProNGF in Prodromal Alzheimer ’s Disease

  • Elliott J. Mufson
  • Scott E. Counts
  • S. Peng
  • Margaret Fahnestock
Conference paper
Part of the Advances in Behavioral Biology book series (ABBI, volume 57)


Nerve Growth Factor Mild Cognitive Impairment Cholinergic Basal Forebrain Neuron Cholinergic Basal Forebrain Mature Nerve Growth Factor 
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  1. 1.
    Mesulam MM, Geula C. Nucleus basalis (Ch4) and cortical cholinergic innervation in the human brain: observations based on the distribution of acetylcholinesterase and choline acetyltransferase. J Comp Neurol 1988;275(2):216–240.PubMedCrossRefGoogle Scholar
  2. 2.
    Mesulam MM, Mufson EJ, Levey AI, Wainer BH. 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 1983;214(2):170–197.PubMedCrossRefGoogle Scholar
  3. 3.
    Bartus RT, Dean RL 3rd, Beer B, Lippa AS. The cholinergic hypothesis of geriatric memory dysfunction. Science 1982;217(4558):408–414.PubMedCrossRefGoogle Scholar
  4. 4.
    Mufson EJ, Bothwell M, Kordower JH. Loss of nerve growth factor receptor-containing neurons in Alzheimer's disease: a quantitative analysis across subregions of the basal forebrain. Exp Neurol 1989;105(3):221–232.PubMedCrossRefGoogle Scholar
  5. 5.
    Whitehouse PJ, Price DL, Clark AW, et al. Alzheimer disease: evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol 1981;10(2):122–126.PubMedCrossRefGoogle Scholar
  6. 6.
    Kaplan DR, Miller FD, Signal transduction by the neurotrophin receptors. Curr Opin Cell Biol 1997;9(2):213–221.PubMedCrossRefGoogle Scholar
  7. 7.
    Lad SP, Neet KE, Mufson EJ, Nerve growth factor: structure, function and therapeutic implications for Alzheimer's disease. Curr Drug Target CNS Neurol Disord 2003;2(5):315–334.CrossRefGoogle Scholar
  8. 8.
    Sofroniew MV, Howe CL, Mobley WC. Nerve growth factor signaling, neuroprotection, and neural repair. Annu Rev Neurosci 2001;24:1217–1281.PubMedCrossRefGoogle Scholar
  9. 9.
    Chao MV, Hempstead BL. p75 and Trk: a two-receptor system. Trends Neurosci 1995;18(7):321–326.PubMedCrossRefGoogle Scholar
  10. 10.
    Bothwell M. Functional interactions of neurotrophins and neurotrophin receptors. Annu Rev Neurosci 1995;18:223–253.PubMedCrossRefGoogle Scholar
  11. 11.
    Fahnestock M, Yu G, Coughlin MD. ProNGF: a neurotrophic or an apoptotic molecule? Prog Brain Res 2004;146:107–110.Google Scholar
  12. 12.
    Fahnestock M, Michalski B, Xu B, Coughlin MD. The precursor pro-nerve growth factor is the predominant form of nerve growth factor in brain and is increased in Alzheimer's disease. Mol Cell Neurosci 2001;18(3):210–220.PubMedCrossRefGoogle Scholar
  13. 13.
    Sobreviela T, Clary DO, Reichardt LF, et al. TrkA-immunoreactive profiles in the central nervous system: co-localization with neurons containing p75 nerve growth factor receptor, choline acetyltransferase, and serotonin. J Comp Neurol 1994;350(4):587–611.PubMedCrossRefGoogle Scholar
  14. 14.
    Appel SH. A unifying hypothesis for the cause of amyotrophic lateral sclerosis, parkinsonism, and Alzheimer disease. Ann Neurol 1981;10(6):499–505.PubMedCrossRefGoogle Scholar
  15. 15.
    Hefti F, Hartikka J, Knusel B, Function of neurotrophic factors in the adult and aging brain and their possible use in the treatment of neurodegenerative diseases. Neurobiol Aging 1989;10(2):515–533.PubMedCrossRefGoogle Scholar
  16. 16.
    Kordower JH, Mufson EF. NGF and Alzheimer's disease: unfulfilled promise and untapped potential. Neurobiol Aging 1989;10(5):543–544.PubMedCrossRefGoogle Scholar
  17. 17.
    Bennett DA, Wilson RS, Schneider JA, et al. Natural history of mild cognitive impairment in older persons. Neurology 2002;59(2):198–205.PubMedGoogle Scholar
  18. 18.
    Counts SE, Nadeem M, Wuu J, et al. Reduction of cortical TrkA but not p75(NTR) protein in early-stage Alzheimer's disease. Ann Neurol 2004;56(4):520–531.PubMedCrossRefGoogle Scholar
  19. 19.
    Gilmor ML, Erickson JD, Varoqui H, et al. Preservation of nucleus basalis neurons containing choline acetyltransferase and the vesicular acetylcholine transporter in the elderly with mild cognitive impairment and early Alzheimer's disease. J Comp Neurol 1999;411(4):693–704.PubMedCrossRefGoogle Scholar
  20. 20.
    Kordower JH, Chu Y, Stebbins GT, et al. Loss and atrophy of layer II entorhinal cortex neurons in elderly people with mild cognitive impairment. Ann Neurol 2001;49(2):202–213.PubMedCrossRefGoogle Scholar
  21. 21.
    Mufson, Ma SY, Cochran EJ, et al. Loss of nucleus basalis neurons containing trkA immunoreactivity in individuals with mild cognitive impairment and early Alzheimer’s disease. J Comp Neurol 2000;427(1):19–30.PubMedCrossRefGoogle Scholar
  22. 22.
    Mufson EJ, Ma SY, Dills J, et al. Loss of basal forebrain p75(NTR) immunoreactivity in subjects with mild cognitive impairment and Alzheimer's disease, J Comp Neurol 2002;443(2):136–153.PubMedCrossRefGoogle Scholar
  23. 23.
    DeKosky ST, Ikonomovic M, Styren SD, et al. Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment. Ann Neurol 2002;51(2):145–155.PubMedCrossRefGoogle Scholar
  24. 24.
    Davies P, Malone AJ. Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet 1976;2(8000):1403.PubMedCrossRefGoogle Scholar
  25. 25.
    Peng S, Wuu J, Mufson EJ, Fahnestock M. Increased proNGF Levels in subjects with mild cognitive impairment and mild Alzheimer's disease. J Neuropathol Exp Neurol 2004;63(6):641–649.PubMedGoogle Scholar
  26. 26.
    Mufson EJ, Ikonomovic SD, Styren SE, et al. Preservation of brain nerve growth factor in mild cognitive impairment and Alzheimer disease. Arch Neurol 2003;60(8):1143–1148.PubMedCrossRefGoogle Scholar
  27. 27.
    Lee R, Kermani P, Teng KK, Hempstead BL. Regulation of cell survival by secreted proneurotrophins. Science 2001;294(5548):1945–1948.PubMedCrossRefGoogle Scholar
  28. 28.
    Barrett GL. The p75 neurotrophin receptor and neuronal apoptosis. Prog Neurobiol 2000;61(2):205–229.PubMedCrossRefGoogle Scholar
  29. 29.
    Nykjaer A, Lee R, Teng KK, et al. Sortilin is essential for proNGF-induced neuronal cell death. Nature 2004;427(6977):843–848.PubMedCrossRefGoogle Scholar
  30. 30.
    Roux PP, Barker PA. Neurotrophin signaling through the p75 neurotrophin receptor. Prog Neurobiol 2002;67(3):203–233.PubMedCrossRefGoogle Scholar
  31. 31.
    Mamidipudi V, Wooten MW. Dual role for p75(NTR) signaling in survival and cell death: can intracellular mediators provide an explanation? J Neurosci Res 2002;68(4):373–384.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Elliott J. Mufson
    • 1
  • Scott E. Counts
  • S. Peng
  • Margaret Fahnestock
  1. 1.Rush University Medical School, Department of Neurological SciencesChicagoUSA

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