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Gene Expression Profiles of Cholinergic Nucleus Basalis Neurons in Alzheimer's Disease

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Abstract

Cholinergic neurons of the nucleus basalis (NB) are selectively vulnerable in Alzheimer's disease (AD), yet the molecular mechanisms associated with their dysfunction remain unknown. We used single cell RNA amplification and custom array technology to examine the expression of functional classes of mRNAs found in anterior NB neurons from normal aged and AD subjects. mRNAs encoding neurotrophin receptors, synaptic proteins, protein phosphatases, and amyloid-related proteins were evaluated. We found that trkB and trkC mRNAs were selectively down-regulated in NB neurons, whereas p75NTR mRNA levels remained stable in end stage AD. TrkA mRNA was reduced by approximately 28%, but did not reach statistical significance. There was a down-regulation of synaptophysin, synaptotagmin, and protein phosphatases PP1α and PP1β mRNAs in AD. In contrast, we found a selective up-regulation of cathepsin D mRNA in NB neurons in AD brain. Thus, anterior NB neurons undergo selective alterations in gene expression in AD. These results may provide clues to the molecular pathogenesis of NB neuronal degeneration during AD.

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REFERENCES

  1. Bartus, R. T., Dean, R. L., 3rd, Beer, B., and Lippa, A. S. 1982. The cholinergic hypothesis of geriatric memory dysfunction. Science 217:408-414.

    Google Scholar 

  2. Bierer, L. M., Haroutunian, V., Gabriel, 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 severity in Alzheimer's disease: relative importance of the cholinergic deficits. J. Neurochem. 64:749-760.

    Google Scholar 

  3. Geula, C. 1998. Abnormalities of neural circuitry in Alzheimer's disease: hippocampus and cortical cholinergic innervation. Neurology 51:S18-S29; discussion S65-S67.

    Google Scholar 

  4. Wilcock, G. K., Esiri, M. M., Bowen, D. M., and Smith, C. C. 1982. Alzheimer's disease. Correlation of cortical choline acetyltransferase activity with the severity of dementia and histological abnormalities. J. Neurol. Sci. 57:407-417.

    Google Scholar 

  5. 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.

    Google Scholar 

  6. Baxter, M. G. and Chiba, A. A. 1999. Cognitive functions of the basal forebrain. Curr. Opin. Neurobiol. 9:178-183.

    Google Scholar 

  7. Davies, P. and Maloney, A. J. 1976. Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet 2:1403.

    Google Scholar 

  8. Mufson, E. J., Bothwell, M., and Kordower, J. H. 1989. 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.

    Google Scholar 

  9. Whitehouse, P. J., Price, D. L., Struble, R. G., Clark, A. W., Coyle, J. T., and Delon, M. R. 1982. Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain. Science 215:1237-1239.

    Google Scholar 

  10. Chu, Y., Cochran, E. J., Bennett, D. A., Mufson, E. J., and Kordower, J. H. 2001. Down-regulation of trkA mRNA within nucleus basalis neurons in individuals with mild cognitive impairment and Alzheimer's disease. J. Comp. Neurol. 437:296-307.

    Google Scholar 

  11. Mufson, E. J., Ma, S. Y., Cochran, E. J., Bennett, D. A., Beckett, L. A., Jaffar, S., Saragovi, H. U., and Kordower, J. H. 2000. Loss of nucleus basalis neurons containing trkA immunoreactivity in individuals with mild cognitive impairment and early Alzheimer's disease. J. Comp. Neurol. 427:19-30.

    Google Scholar 

  12. Mufson, E. J., Ma, S. Y., Dills, J., Cochran, E. J., Leurgans, S., Wuu, J., Bennett, D. A., Jaffar, S., Gilmor, M. L., Levey, A. I., and Kordower, J. H. 2002. Loss of basal forebrain P75(NTR) immunoreactivity in subjects with mild cognitive impairment and Alzheimer's disease. J. Comp. Neurol. 443:136-153.

    Google Scholar 

  13. Kordower, J. H., Gash, D. M., Bothwell, M., Hersh, L., 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 10:67-74.

    Google Scholar 

  14. 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.

    Google Scholar 

  15. Davis, K. L., Mohs, R. C., Marin, D., Purohit, D. P., Perl, D. P., Lantz, M., Austin, G., and Haroutunian, V. 1999. Cholinergic markers in elderly patients with early signs of Alzheimer disease. JAMA 281:1401-1406.

    Google Scholar 

  16. DeKosky, S. T., Harbaugh, R. E., Schmitt, F. A., Bakay, R. A., Chui, H. C., Knopman, D. S., Reeder, T. M., Shetter, A. G., Senter, H. J., and Markesbery, W. R. 1992. Cortical biopsy in Alzheimer's disease: diagnostic accuracy and neurochemical, neuropathological, and cognitive correlations. Intraventricular Bethanecol Study Group. Ann. Neurol. 32:625-632.

    Google Scholar 

  17. DeKosky, S. T., Ikonomovic, M. D., Styren, S. D., Beckett, L., Wisniewski, S., Bennett, D. A., Cochran, E. J., Kordower, J. H., and Mufson, E. J. 2002. Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment. Ann. Neurol. 51:145-155.

    Google Scholar 

  18. Gilmor, M. L., Erickson, J. D., Varoqui, H., Hersh, L. B., Bennett, D. A., Cochran, E. J., Mufson, E. J., and Levey, A. I. 1999. 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. 411:693-704.

    Google Scholar 

  19. Cullen, K. M. and Halliday, G. M. 1998. Neurofibrillary degeneration and cell loss in the nucleus basalis in comparison to cortical Alzheimer pathology. Neurobiol. Aging 19:297-306.

    Google Scholar 

  20. Price, J. L., Davis, P. B., Morris, J. C., and White, D. L. 1991. The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer's disease. Neurobiol. Aging 12:295-312.

    Google Scholar 

  21. Sassin, I., Schultz, C., Thal, D. R., Rub, U., Arai, K., Braak, E., and Braak, H. 2000. Evolution of Alzheimer's disease-related cytoskeletal changes in the basal nucleus of Meynert. Acta Neuropathol. (Berl.) 100:259-269.

    Google Scholar 

  22. Alonso, A. C., Grundke-Iqbal, I., and Iqbal, K. 1996. Alzheimer's disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules. Nat. Med. 2:783-787.

    Google Scholar 

  23. Cleveland, D. W., Hwo, S. Y., and Kirschner, M. W. 1977. Purification of tau, a microtubule-associated protein that induces assembly of microtubules from purified tubulin. J. Mol. Biol. 116:207-225.

    Google Scholar 

  24. Callahan, L. M. and Coleman, P. D. 1995. Neurons bearing neurofibrillary tangles are responsible for selected synaptic deficits in Alzheimer's disease. Neurobiol. Aging 16:311-314.

    Google Scholar 

  25. Ginsberg, S. D., Hemby, S. E., Lee, V. M., Eberwine, J. H., and Trojanowski, J. Q. 2000. Expression profile of transcripts in Alzheimer's disease tangle-bearing CA1 neurons. Ann. Neurol. 48:77-87.

    Google Scholar 

  26. Stamer, K., Vogel, R., Thies, E., Mandelkow, E., and Mandelkow, E. M. 2002. Tau blocks traffic of organelles, neurofilaments, and APP vesicles in neurons and enhances oxidative stress. J. Cell. Biol. 156:1051-1063.

    Google Scholar 

  27. Masliah, E., Mallory, M., Hansen, L., DeTeresa, R., Alford, M., and Terry R. 1994. Synaptic and neuritic alterations during the progression of Alzheimer's disease. Neurosci. Lett. 174:67-72.

    Google Scholar 

  28. Selkoe, D. J. 1999. Translating cell biology into therapeutic advances in Alzheimer's disease. Nature 399:A23-A31.

    Google Scholar 

  29. Struble, R. G., Cork, L. C., Whitehouse, P. J., and Price, D. L. 1982. Cholinergic innervation in neuritic plaques. Science 216: 413-415.

    Google Scholar 

  30. Callahan, L. M., Chow, N., Cheetham, J. E., Cox, C., and Coleman, P. D. 1998. Analysis of message expression in single neurons of Alzheimer's disease brain. Neurobiol. Aging 19:S99-S105.

    Google Scholar 

  31. Chow, N., Cox, C., Callahan, L. M., Weimer, J. M., Guo, L., and Coleman, P. D. 1998. Expression profiles of multiple genes in single neurons of Alzheimer's disease. Proc. Natl. Acad. Sci. USA 95:9620-9625.

    Google Scholar 

  32. Crino, P., Khodakhah, K., Becker, K., Ginsberg, S., Hemby, S., and Eberwine, J. 1998. Presence and phosphorylation of transcription factors in developing dendrites. Proc. Natl. Acad. Sci. USA 95:2313-2318.

    Google Scholar 

  33. Eberwine, J., Yeh, H., Miyashiro, K., Cao, Y., Nair, S., Finnell, R., Zettel, M., and Coleman, P. 1992. Analysis of gene expression in single live neurons. Proc. Natl. Acad. Sci. USA 89:3010-3014.

    Google Scholar 

  34. Eberwine J., Kacharmina, J. E., Andrews, C., Miyashiro, K., McIntosh, T., Becker, K., Barrett, T., Hinkle, D., Dent, G., and Marciano, P. 2001. mRNA expression analysis of tissue sections and single cells. J. Neurosci. 21:8310-8314.

    Google Scholar 

  35. Ginsberg, S. D., Crino, P. B., Hemby, S. E., Weingarten, J. A., Lee, V. M., Eberwine, J. H., and Trojanowski, J. Q. 1999. Predominance of neuronal mRNAs in individual Alzheimer's disease senile plaques. Ann. Neurol. 45:174-181.

    Google Scholar 

  36. Bennett, D. A., Wilson, R. S., Schneider, J. A., Evans, D. A., Beckett, L. A., Aggarwal, N. T., Barnes, L. L., Fox, J. H., and Bach, J. 2002. Natural history of mild cognitive impairment in older persons. Neurology, 59:198-205.

    Google Scholar 

  37. Kordower, J. H., Chu, Y., Stebbins, G. T., DeKosky, S. T., Cochran, E. J., Bennett, D., and Mufson, E. J. 2001. Loss and atrophy of layer II entorhinal cortex neurons in elderly people with mild cognitive impairment. Ann Neurol. 49:202-213.

    Google Scholar 

  38. Mufson, E. J., Chen, E. Y., Cochran, E. J., Beckett, L. A., Bennett, D. A., and Kordower, J. H. 1999. Entorhinal cortex beta-amyloid load in individuals with mild cognitive impairment. Exp. Neurol. 158:469-490.

    Google Scholar 

  39. Bennett, D. A., Shannon, K. M., Beckett, L. A., Goetz, C. G., and Wilson, R. S. 1997. Metric properties of nurses' ratings of parkinsonian signs with a modified Unified Parkinson's Disease Rating Scale. Neurology 49:1580-1587.

    Google Scholar 

  40. Bennett, D. A., Shannon, K. M., Beckett, L. A., and Wilson, R. S. 1999. Dimensionality of parkinsonian signs in aging and Alzheimer's disease. J. Gerontol. A. Biol. Sci. Med. Sci. 54:M191-M196.

    Google Scholar 

  41. Goldstein, L. B., Bertels, C., and Davis, J. N. 1989. Interrater reliability of the NIH stroke scale. Arch. Neurol. 46:660-662.

    Google Scholar 

  42. Goldstein, L. B. and Samsa, G. P. 1997. Reliability of the National Institutes of Health Stroke Scale. Extension to nonneurologists in the context of a clinical trial. Stroke 28:307-310.

    Google Scholar 

  43. Folstein, M. F., Folstein, S. E., and McHugh, P. R. 1975. "Minimental state". A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 12:189-198.

    Google Scholar 

  44. Morris, J. C., Heyman, A., Mohs, R. C., Hughes, J. P., van Belle, G., Fillenbaum, G., Mellits, E. D., and Clark, C. 1989. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease. Neurology 39:1159-1165.

    Google Scholar 

  45. Beckett, L. A., Wilson, R. S., Bennett, D. A., and Morris, M. C. 1997. Around the WORLD backward: an algorithm for scoring the MMSE WORLD item. Neurology 48:1733-1734.

    Google Scholar 

  46. Pittman, J., Andrews, H., Tatemichi, T., Link, B., Struening, E., Stern, Y., and Mayeux, R. 1992. Diagnosis of dementia in a heterogeneous population. A comparison of paradigm-based diagnosis and physician's diagnosis. Arch. Neurol. 49:461-467.

    Google Scholar 

  47. Snowdon, D. A., Kemper, S. J., Mortimer, J. A., Greiner, L. H., Wekstein, D. R., and Markesbery, W. R. 1996. Linguistic ability in early life and cognitive function and Alzheimer's disease in late life. Findings from the Nun Study. JAMA 275:528-532.

    Google Scholar 

  48. McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., and Stadlan, E. M. 1984. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 34:939-944.

    Google Scholar 

  49. Hyman, B. T. and Trojanowski, J. Q. 1997. Consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working Group on diagnostic criteria for the neuropathological assessment of Alzheimer disease. J. Neuropathol. Exp. Neurol. 56:1095-1097.

    Google Scholar 

  50. Mirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., van Belle, G., and Berg, L. 1991. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology 41:479-486.

    Google Scholar 

  51. Ginsberg, S. D., Crino, P. B., Lee, V. M., Eberwine, J. H., and Trojanowski, J. Q. 1997. Sequestration of RNA in Alzheimer's disease neurofibrillary tangles and senile plaques. Ann. Neurol. 41:200-209.

    Google Scholar 

  52. Ginsberg, S. D., Galvin, J. E., Chiu, T. S., Lee, V. M., Masliah, E., and Trojanowski, J. Q. 1998. RNA sequestration to pathological lesions of neurodegenerative diseases. Acta Neuropathol. (Berl.) 96:487-494.

    Google Scholar 

  53. Van Deerlin, V. M. D., Ginsberg, S. D., Lee, V. M.-Y., and Trojanowski, J. Q. 2002. The use of fixed human postmortem brain tissue to study mRNA expression in neurodegenerative diseases: applications of microdissection and mRNA amplification. Pages 201-235, in Geschwind, D. H. and Gregg, J. (eds.), Microarrays for the Neurosciences: An Essential Guide, MIT Press, Boston.

    Google Scholar 

  54. 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.

    Google Scholar 

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

    Google Scholar 

  56. Schatteman, G. C., Gibbs, L., Lanahan, A. A., Claude, P., and Bothwell, M. 1988. Expression of NGF receptor in the developing and adult primate central nervous system. J. Neurosci. 8:860-873.

    Google Scholar 

  57. Hancock, W. W., Becker, G. J., and Atkins, R. C. 1982. A comparison of fixatives and immunohistochemical technics for use with monoclonal antibodies to cell surface antigens. Am. J. Clin. Pathol. 78:825-831.

    Google Scholar 

  58. Roses, A. D. and Saunders, A. M. 1994. APOE is a major susceptibility gene for Alzheimer's disease. Curr. Opin. Biotechnol. 5:663-667.

    Google Scholar 

  59. Che, S. and Ginsberg, S. D. 2002. Amplification of transcripts using terminal continuation. Nat. Biotechnol. Submitted.

  60. Ginsberg, S. D. and Che, S. 2002. RNA amplification in brain tissues. Neurochem. Res. 27:981-992.

    Google Scholar 

  61. Ginsberg, S. D., Schmidt, M. L., Crino, P. B., Eberwine, J. H., Lee, V. M.-Y., and Trojanowski, J. Q. 1999. Molecular pathology of Alzheimer's disease and related disorders. Pages 603-653, in Peters, A. and Morrison, J. H. (eds.), Cerebral Cortex, vol. 14. Neurodegenerative and Age-related Changes in Structure and Function of Cerebral Cortex, Kluwer Academic/Plenum, New York.

    Google Scholar 

  62. Hemby, S. E., Ginsberg, S. D., Brunk, B., Arnold, S. E., Overton, C., Trojanowski, J. Q., and Eberwine, J. H. 2002. A mRNA expression profile for schizophrenia: single-neuron transcription patterns from the entorhinal cortex. Arch. Gen. Psychiat. 59:631-640.

    Google Scholar 

  63. Hemby, S. E. Trojanowski, J. Q., and Ginsberg, S. D. 2002. Neuron specific age related decreases in dopamine receptor subtype mRNAs. J. Comp. Neurol., in press.

  64. Barbacid, M. 1994. The Trk family of neurotrophin receptors. J Neurobiol 25:1386-1403.

    Google Scholar 

  65. Boissiere, F., Faucheux, B., Ruberg, M., Agid, Y., and Hirsch, E. C. 1997. Decreased TrkA gene expression in cholinergic neurons of the striatum and basal forebrain of patients with Alzheimer's disease. Exp. Neurol. 145:245-252.

    Google Scholar 

  66. 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 8:25-29.

    Google Scholar 

  67. 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 

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

    Google Scholar 

  69. Gibbs, R. B. and Pfaff, D. W. 1992. Effects of estrogen and fimbria /fornix transection on p75NGFR and ChAT expression in the medial septum and diagonal band of Broca. Exp. Neurol. 116:23-39.

    Google Scholar 

  70. Kordower, J. H., Chen, E. Y., Sladek, J. R., Jr., and Mufson, E. J. 1994. trk-immunoreactivity in the monkey central nervous system: forebrain. J. Comp. Neurol. 349:20-35.

    Google Scholar 

  71. Sobreviela, T., Clary, D. O., Reichardt, L. F., Brandabur, M. M., Kordower, J. H., and Mufson, E. J. 1994. 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.

    Google Scholar 

  72. Boissiere, F., Faucheux, B., Agid, Y., and Hirsch, E. C. 1997. Expression of catalytic trkB gene in the striatum and the basal forebrain of patients with Alzheimer's disease: an in situ hybridization study. Neurosci. Lett. 221:141-144.

    Google Scholar 

  73. Salehi, A., Verhaagen, J., Dijkhuizen, P. A., and Swaab, D. F. 1996. Co-localization of high-affinity neurotrophin receptors in nucleus basalis of Meynert neurons and their differential reduction in Alzheimer's disease. Neuroscience 75:373-387.

    Google Scholar 

  74. Mufson, E. J., Kroin, J. S., Sendera, T. J., and Sobreviela, T. 1999. Distribution and retrograde transport of trophic factors in the central nervous system: functional implications for the treatment of neurodegenerative diseases. Prog. Neurobiol. 57:451-484.

    Google Scholar 

  75. Wetmore, C., Cao, Y. H., Pettersson, R. F., and Olson, L. 1991. Brain-derived neurotrophic factor: subcellular compartmentalization and interneuronal transfer as visualized with anti-peptide antibodies. Proc. Natl. Acad. Sci. USA 88:9843-9847.

    Google Scholar 

  76. Hashimoto, Y., Abiru, Y., Nishio, C., and Hatanaka, H. 1999. Synergistic effects of brain-derived neurotrophic factor and ciliary neurotrophic factor on cultured basal forebrain cholinergic neurons from postnatal 2-week-old rats. Brain Res. Dev. Brain Res. 115:25-32.

    Google Scholar 

  77. Nonomura, T., Nishio, C., Lindsay, R. M., and Hatanaka, H. 1995. Cultured basal forebrain cholinergic neurons from postnatal rats show both overlapping and non-overlapping responses to the neurotrophins. Brain. Res. 683:129-139.

    Google Scholar 

  78. Allen, S. J., Wilcock, G. K., and Dawbarn, D. 1999. Profound and selective loss of catalytic TrkB immunoreactivity in Alzheimer's disease. Biochem. Biophys. Res. Commun. 264:648-651.

    Google Scholar 

  79. Ferrer, I., Marin, C., Rey, M. J., Ribalta, T., Goutan, E., Blanco, R., Tolosa, E., and Marti, E. 1999. BDNF and full-length and truncated TrkB expression in Alzheimer disease. Implications in therapeutic strategies. J. Neuropathol. Exp. Neurol. 58:729-739.

    Google Scholar 

  80. Hock, C., Heese, K., Hulette, C., Rosenberg, C., and Otten, U. 2000. Region-specific neurotrophin imbalances in Alzheimer disease: decreased levels of brain-derived neurotrophic factor and increased levels of nerve growth factor in hippocampus and cortical areas. Arch. Neurol. 57:846-851.

    Google Scholar 

  81. Boissiere, F., Hunot, S., Faucheux, B., Mouatt-Prigent, A., Agid, Y., and Hirsch, E. C. 1994. High affinity neurotrophin receptors in cholinergic neurons in the human brain. C. R. Acad. Sci. III 317:997-1003.

    Google Scholar 

  82. Savaskan, E., Muller-Spahn, F., Olivieri, G., Bruttel, S., Otten, U., Rosenberg, C., Hulette, C., and Hock, C. 2000. Alterations in trk A, trk B and trk C receptor immunoreactivities in parietal cortex and cerebellum in Alzheimer's disease. Eur. Neurol. 44:172-180.

    Google Scholar 

  83. Masliah, E., Mallory, M., Alford, M., DeTeresa, R., Hansen, L. A., McKeel, D. W., Jr., and Morris, J. C. 2001. Altered expression of synaptic proteins occurs early during progression of Alzheimer's disease. Neurology 56:127-129.

    Google Scholar 

  84. Davidsson, P. and Blennow, K. 1998. Neurochemical dissection of synaptic pathology in Alzheimer's disease. Int. Psychogeriatr. 10:11-23.

    Google Scholar 

  85. DeKosky, S. T. and Scheff, S. W. 1990. Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Ann. Neurol. 27:457-464.

    Google Scholar 

  86. Loring, J. F., Wen, X., Lee, J. M., Seilhamer, J., and Somogyi, R. 2001. A gene expression profile of Alzheimer's disease. DNA Cell Biol. 20:683-695.

    Google Scholar 

  87. Fernandez-Chacon, R. and Sudhof, T. C. 1999. Genetics of synaptic vesicle function: toward the complete functional anatomy of an organelle. Annu. Rev. Physiol. 61:753-776.

    Google Scholar 

  88. Iqbal, K., Alonso, A. D., Gondal, J. A., Gong, C. X., Haque, N., Khatoon, S., Sengupta, A., Wang, J. Z., and Grundke-Iqbal, I. 2000. Mechanism of neurofibrillary degeneration and pharmacologic therapeutic approach. J. Neural. Transm. Suppl. 59:213-222.

    Google Scholar 

  89. Baum, L., Seger, R., Woodgett, J. R., Kawabata, S., Maruyama, K., Koyama, M., Silver, J., and Saitoh, T. 1995. Overexpressed tau protein in cultured cells is phosphorylated without formation of PHF: implication of phosphoprotein phosphatase involvement. Brain Res. Mol. Brain Res. 34:1-17.

    Google Scholar 

  90. Merrick, S. E., Trojanowski, J. Q., and Lee, V. M. 1997. Selective destruction of stable microtubules and axons by inhibitors of protein serine/threonine phosphatases in cultured human neurons. J. Neurosci. 17:5726-5737.

    Google Scholar 

  91. Pearson, R. C., Esiri, M. M., Hiorns, R. W., Wilcock, G. K., and Powell, T. P. 1985. Anatomical correlates of the distribution of the pathological changes in the neocortex in Alzheimer disease. Proc. Natl. Acad. Sci. USA 82:4531-4534.

    Google Scholar 

  92. Brun, A. and Englund, E. 1981. Regional pattern of degeneration in Alzheimer's disease: neuronal loss and histopathological grading. Histopathology 5:549-564.

    Google Scholar 

  93. Cataldo, A. M., Barnett, J. L., Berman, S. A., Li, J., Quarless, S., Bursztajn, S., Lippa, C., and Nixon, R. A. 1995. Gene expression and cellular content of cathepsin D in Alzheimer's disease brain: evidence for early up-regulation of the endosomal-lysosomal system. Neuron 14:671-680.

    Google Scholar 

  94. Cataldo, A. M., Hamilton, D. J., Barnett, J. L., Paskevich, P. A., and Nixon, R. A. 1996. Properties of the endosomal-lysosomal system in the human central nervous system: disturbances mark most neurons in populations at risk to degenerate in Alzheimer's disease. J. Neurosci. 16:186-199.

    Google Scholar 

  95. Cataldo, A. M., Barnett, J. L., Pieroni, C., and Nixon, R. A. 1997. Increased neuronal endocytosis and protease delivery to early endosomes in sporadic Alzheimer's disease: neuropathologic evidence for a mechanism of increased beta-amyloidogenesis. J. Neurosci. 17:6142-6151.

    Google Scholar 

  96. Mathews, P. M., Guerra, C. B., Jiang, Y., Grbovic, O. M., Kao, B. H., Schmidt, S. D., Dinakar, R., Mercken, M., Hille-Rehfeld, A., Rohrer, J., Mehta, P., Cataldo, A. M., and Nixon, R. A. 2002. Alzheimer's disease-related overexpression of the cation-dependent mannose 6-phosphate receptor increases Abeta secretion: role for altered lysosomal hydrolase distribution in beta-amyloidogenesis. J. Biol. Chem. 277:5299-5307.

    Google Scholar 

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Authors and Affiliations

  1. Department of Neurological Sciences, Rush Alzheimer's Disease Research Center, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL, 60612

    Elliott J. Mufson & Scott E. Counts

  2. Center for Dementia Research, Nathan Kline Institute, Department of Psychiatry, New York University School of Medicine, Orangeburg, NY, 10902

    Stephen D. Ginsberg

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  1. Elliott J. Mufson
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  2. Scott E. Counts
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  3. Stephen D. Ginsberg
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Mufson, E.J., Counts, S.E. & Ginsberg, S.D. Gene Expression Profiles of Cholinergic Nucleus Basalis Neurons in Alzheimer's Disease. Neurochem Res 27, 1035–1048 (2002). https://doi.org/10.1023/A:1020952704398

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  • DOI: https://doi.org/10.1023/A:1020952704398

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