Life and death of neurons in the aging brain

Science

Volumn 278, Issue 5337, 1997, Pages 412-419

  Morrison, John H ^a   Hof, Patrick R ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ESTROGEN; NEUROFILAMENT PROTEIN;

AGING; ALZHEIMER DISEASE; ARTICLE; CELL DEATH; DEGENERATIVE DISEASE; DEMENTIA; DENTATE GYRUS; ELECTROPHYSIOLOGY; ENTORHINAL CORTEX; GRANULE CELL; HIPPOCAMPUS; LEWY BODY; NEOCORTEX; NERVE CELL; NERVE CELL DEGENERATION; NEUROFIBRILLARY TANGLE; PICK PRESENILE DEMENTIA; PRIORITY JOURNAL; SENILE PLAQUE;

NASA DISCIPLINE NEUROSCIENCE; NON-NASA CENTER;

AGING; ALZHEIMER DISEASE; ANIMALS; CELL DEATH; CELL SURVIVAL; ENTORHINAL CORTEX; ESTROGENS; FEMALE; HIPPOCAMPUS; HUMANS; MALE; MEMORY; NEOCORTEX; NERVE DEGENERATION; NEUROFIBRILLARY TANGLES; NEUROFILAMENT PROTEINS; NEURONS;

EID: 0030698871     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.278.5337.412     Document Type: Article

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53. H. Braak and E. Braak, Acta Neuropathol. 68, 325 (1985); H. Crystal et al., Neurology 38, 1682 (1988); R. Katzman et al., Ann. Neurol. 23, 138 (1988); B. M. Hubbard, G. W. Fenton, J. M. Anderson, Neuropathol. Appl. Neurobiol. 16, 111 (1990); H. Braak and E. Braak, Acta Neuropathol. 82, 239 (1991); D. W. Dickson et al., Neurobiol. Aging 13, 179 (1992); J. C. Morris et al., Neurology 41, 469 (1991); J. L. Price, P. B. Davis, J. C. Morris, D. L. White, Neurobiol. Aging 12, 295 (1991); L. Berg, D. W. McKeel, P. Miller, J. Baty, J. C. Morris, Arch. Neurol. 50, 349 (1993).
54. H. Braak and E. Braak, Acta Neuropathol. 68, 325 (1985); H. Crystal et al., Neurology 38, 1682 (1988); R. Katzman et al., Ann. Neurol. 23, 138 (1988); B. M. Hubbard, G. W. Fenton, J. M. Anderson, Neuropathol. Appl. Neurobiol. 16, 111 (1990); H. Braak and E. Braak, Acta Neuropathol. 82, 239 (1991); D. W. Dickson et al., Neurobiol. Aging 13, 179 (1992); J. C. Morris et al., Neurology 41, 469 (1991); J. L. Price, P. B. Davis, J. C. Morris, D. L. White, Neurobiol. Aging 12, 295 (1991); L. Berg, D. W. McKeel, P. Miller, J. Baty, J. C. Morris, Arch. Neurol. 50, 349 (1993).
55. H. Braak and E. Braak, Acta Neuropathol. 68, 325 (1985); H. Crystal et al., Neurology 38, 1682 (1988); R. Katzman et al., Ann. Neurol. 23, 138 (1988); B. M. Hubbard, G. W. Fenton, J. M. Anderson, Neuropathol. Appl. Neurobiol. 16, 111 (1990); H. Braak and E. Braak, Acta Neuropathol. 82, 239 (1991); D. W. Dickson et al., Neurobiol. Aging 13, 179 (1992); J. C. Morris et al., Neurology 41, 469 (1991); J. L. Price, P. B. Davis, J. C. Morris, D. L. White, Neurobiol. Aging 12, 295 (1991); L. Berg, D. W. McKeel, P. Miller, J. Baty, J. C. Morris, Arch. Neurol. 50, 349 (1993).
56. H. Braak and E. Braak, Acta Neuropathol. 68, 325 (1985); H. Crystal et al., Neurology 38, 1682 (1988); R. Katzman et al., Ann. Neurol. 23, 138 (1988); B. M. Hubbard, G. W. Fenton, J. M. Anderson, Neuropathol. Appl. Neurobiol. 16, 111 (1990); H. Braak and E. Braak, Acta Neuropathol. 82, 239 (1991); D. W. Dickson et al., Neurobiol. Aging 13, 179 (1992); J. C. Morris et al., Neurology 41, 469 (1991); J. L. Price, P. B. Davis, J. C. Morris, D. L. White, Neurobiol. Aging 12, 295 (1991); L. Berg, D. W. McKeel, P. Miller, J. Baty, J. C. Morris, Arch. Neurol. 50, 349 (1993).
57. H. Braak and E. Braak, Acta Neuropathol. 68, 325 (1985); H. Crystal et al., Neurology 38, 1682 (1988); R. Katzman et al., Ann. Neurol. 23, 138 (1988); B. M. Hubbard, G. W. Fenton, J. M. Anderson, Neuropathol. Appl. Neurobiol. 16, 111 (1990); H. Braak and E. Braak, Acta Neuropathol. 82, 239 (1991); D. W. Dickson et al., Neurobiol. Aging 13, 179 (1992); J. C. Morris et al., Neurology 41, 469 (1991); J. L. Price, P. B. Davis, J. C. Morris, D. L. White, Neurobiol. Aging 12, 295 (1991); L. Berg, D. W. McKeel, P. Miller, J. Baty, J. C. Morris, Arch. Neurol. 50, 349 (1993).
58. H. Braak and E. Braak, Acta Neuropathol. 68, 325 (1985); H. Crystal et al., Neurology 38, 1682 (1988); R. Katzman et al., Ann. Neurol. 23, 138 (1988); B. M. Hubbard, G. W. Fenton, J. M. Anderson, Neuropathol. Appl. Neurobiol. 16, 111 (1990); H. Braak and E. Braak, Acta Neuropathol. 82, 239 (1991); D. W. Dickson et al., Neurobiol. Aging 13, 179 (1992); J. C. Morris et al., Neurology 41, 469 (1991); J. L. Price, P. B. Davis, J. C. Morris, D. L. White, Neurobiol. Aging 12, 295 (1991); L. Berg, D. W. McKeel, P. Miller, J. Baty, J. C. Morris, Arch. Neurol. 50, 349 (1993).
59. H. Braak and E. Braak, Acta Neuropathol. 68, 325 (1985); H. Crystal et al., Neurology 38, 1682 (1988); R. Katzman et al., Ann. Neurol. 23, 138 (1988); B. M. Hubbard, G. W. Fenton, J. M. Anderson, Neuropathol. Appl. Neurobiol. 16, 111 (1990); H. Braak and E. Braak, Acta Neuropathol. 82, 239 (1991); D. W. Dickson et al., Neurobiol. Aging 13, 179 (1992); J. C. Morris et al., Neurology 41, 469 (1991); J. L. Price, P. B. Davis, J. C. Morris, D. L. White, Neurobiol. Aging 12, 295 (1991); L. Berg, D. W. McKeel, P. Miller, J. Baty, J. C. Morris, Arch. Neurol. 50, 349 (1993).
60. H. Braak and E. Braak, Acta Neuropathol. 68, 325 (1985); H. Crystal et al., Neurology 38, 1682 (1988); R. Katzman et al., Ann. Neurol. 23, 138 (1988); B. M. Hubbard, G. W. Fenton, J. M. Anderson, Neuropathol. Appl. Neurobiol. 16, 111 (1990); H. Braak and E. Braak, Acta Neuropathol. 82, 239 (1991); D. W. Dickson et al., Neurobiol. Aging 13, 179 (1992); J. C. Morris et al., Neurology 41, 469 (1991); J. L. Price, P. B. Davis, J. C. Morris, D. L. White, Neurobiol. Aging 12, 295 (1991); L. Berg, D. W. McKeel, P. Miller, J. Baty, J. C. Morris, Arch. Neurol. 50, 349 (1993).
61. In this context, epidemiologic, clinical, and neuropathologic studies have shown that the characteristics of brain aging in very old individuals differ considerably from those in patients younger than 90 years. The prevalence of dementia is much lower among very old individuals, and it has been suggested that the "oldest-old" population may in fact represent a genetically distinct group. In centenarians, the EC is relatively mildly affected in terms of neuron loss even in patients with AD, and the distribution of NFT and SP lesions in hippocampus and neocortex differs from that in younger individuals [J. J. Hauw et al., Rev. Neurol. 142, 107 (1986); T. Mizutani and H. Shimada, J. Neurol. Sci. 108, 168 (1992); P. Delaère, Y. He, G. Fayet, C. Duyckaerts, J. J. Hauw, Neurobiol. Aging 14, 191 (1993); P. Giannakopoulos, P. R. Hof, M. Surini, J. P. Michel, C. Bouras, Acta Neuropathol. 85, 602 (1993); P. Giannakopoulos et al., Dementia 5, 348 (1994); G. W. Rebeck et al., Neurology 44, 1513 (1994); P. Giannakopoulos et al., Arch. Neurol. 52, 1150 (1995); P. Giannakopoulos, P. R. Hof, C. Bouras, Lancet 346, 1486 (1995); K. Ritchie and D. Kildea, ibid., p. 931; E. Sobel et al., Neurology 45, 903 (1995); T. Asada et al., J. Am. Geriatr. Soc. 44, 151 (1996); N. T. Lautenschlager et al., Neurology 46, 641 (1996)].
62. In this context, epidemiologic, clinical, and neuropathologic studies have shown that the characteristics of brain aging in very old individuals differ considerably from those in patients younger than 90 years. The prevalence of dementia is much lower among very old individuals, and it has been suggested that the "oldest-old" population may in fact represent a genetically distinct group. In centenarians, the EC is relatively mildly affected in terms of neuron loss even in patients with AD, and the distribution of NFT and SP lesions in hippocampus and neocortex differs from that in younger individuals [J. J. Hauw et al., Rev. Neurol. 142, 107 (1986); T. Mizutani and H. Shimada, J. Neurol. Sci. 108, 168 (1992); P. Delaère, Y. He, G. Fayet, C. Duyckaerts, J. J. Hauw, Neurobiol. Aging 14, 191 (1993); P. Giannakopoulos, P. R. Hof, M. Surini, J. P. Michel, C. Bouras, Acta Neuropathol. 85, 602 (1993); P. Giannakopoulos et al., Dementia 5, 348 (1994); G. W. Rebeck et al., Neurology 44, 1513 (1994); P. Giannakopoulos et al., Arch. Neurol. 52, 1150 (1995); P. Giannakopoulos, P. R. Hof, C. Bouras, Lancet 346, 1486 (1995); K. Ritchie and D. Kildea, ibid., p. 931; E. Sobel et al., Neurology 45, 903 (1995); T. Asada et al., J. Am. Geriatr. Soc. 44, 151 (1996); N. T. Lautenschlager et al., Neurology 46, 641 (1996)].
63. In this context, epidemiologic, clinical, and neuropathologic studies have shown that the characteristics of brain aging in very old individuals differ considerably from those in patients younger than 90 years. The prevalence of dementia is much lower among very old individuals, and it has been suggested that the "oldest-old" population may in fact represent a genetically distinct group. In centenarians, the EC is relatively mildly affected in terms of neuron loss even in patients with AD, and the distribution of NFT and SP lesions in hippocampus and neocortex differs from that in younger individuals [J. J. Hauw et al., Rev. Neurol. 142, 107 (1986); T. Mizutani and H. Shimada, J. Neurol. Sci. 108, 168 (1992); P. Delaère, Y. He, G. Fayet, C. Duyckaerts, J. J. Hauw, Neurobiol. Aging 14, 191 (1993); P. Giannakopoulos, P. R. Hof, M. Surini, J. P. Michel, C. Bouras, Acta Neuropathol. 85, 602 (1993); P. Giannakopoulos et al., Dementia 5, 348 (1994); G. W. Rebeck et al., Neurology 44, 1513 (1994); P. Giannakopoulos et al., Arch. Neurol. 52, 1150 (1995); P. Giannakopoulos, P. R. Hof, C. Bouras, Lancet 346, 1486 (1995); K. Ritchie and D. Kildea, ibid., p. 931; E. Sobel et al., Neurology 45, 903 (1995); T. Asada et al., J. Am. Geriatr. Soc. 44, 151 (1996); N. T. Lautenschlager et al., Neurology 46, 641 (1996)].
64. In this context, epidemiologic, clinical, and neuropathologic studies have shown that the characteristics of brain aging in very old individuals differ considerably from those in patients younger than 90 years. The prevalence of dementia is much lower among very old individuals, and it has been suggested that the "oldest-old" population may in fact represent a genetically distinct group. In centenarians, the EC is relatively mildly affected in terms of neuron loss even in patients with AD, and the distribution of NFT and SP lesions in hippocampus and neocortex differs from that in younger individuals [J. J. Hauw et al., Rev. Neurol. 142, 107 (1986); T. Mizutani and H. Shimada, J. Neurol. Sci. 108, 168 (1992); P. Delaère, Y. He, G. Fayet, C. Duyckaerts, J. J. Hauw, Neurobiol. Aging 14, 191 (1993); P. Giannakopoulos, P. R. Hof, M. Surini, J. P. Michel, C. Bouras, Acta Neuropathol. 85, 602 (1993); P. Giannakopoulos et al., Dementia 5, 348 (1994); G. W. Rebeck et al., Neurology 44, 1513 (1994); P. Giannakopoulos et al., Arch. Neurol. 52, 1150 (1995); P. Giannakopoulos, P. R. Hof, C. Bouras, Lancet 346, 1486 (1995); K. Ritchie and D. Kildea, ibid., p. 931; E. Sobel et al., Neurology 45, 903 (1995); T. Asada et al., J. Am. Geriatr. Soc. 44, 151 (1996); N. T. Lautenschlager et al., Neurology 46, 641 (1996)].
65. In this context, epidemiologic, clinical, and neuropathologic studies have shown that the characteristics of brain aging in very old individuals differ considerably from those in patients younger than 90 years. The prevalence of dementia is much lower among very old individuals, and it has been suggested that the "oldest-old" population may in fact represent a genetically distinct group. In centenarians, the EC is relatively mildly affected in terms of neuron loss even in patients with AD, and the distribution of NFT and SP lesions in hippocampus and neocortex differs from that in younger individuals [J. J. Hauw et al., Rev. Neurol. 142, 107 (1986); T. Mizutani and H. Shimada, J. Neurol. Sci. 108, 168 (1992); P. Delaère, Y. He, G. Fayet, C. Duyckaerts, J. J. Hauw, Neurobiol. Aging 14, 191 (1993); P. Giannakopoulos, P. R. Hof, M. Surini, J. P. Michel, C. Bouras, Acta Neuropathol. 85, 602 (1993); P. Giannakopoulos et al., Dementia 5, 348 (1994); G. W. Rebeck et al., Neurology 44, 1513 (1994); P. Giannakopoulos et al., Arch. Neurol. 52, 1150 (1995); P. Giannakopoulos, P. R. Hof, C. Bouras, Lancet 346, 1486 (1995); K. Ritchie and D. Kildea, ibid., p. 931; E. Sobel et al., Neurology 45, 903 (1995); T. Asada et al., J. Am. Geriatr. Soc. 44, 151 (1996); N. T. Lautenschlager et al., Neurology 46, 641 (1996)].
66. In this context, epidemiologic, clinical, and neuropathologic studies have shown that the characteristics of brain aging in very old individuals differ considerably from those in patients younger than 90 years. The prevalence of dementia is much lower among very old individuals, and it has been suggested that the "oldest-old" population may in fact represent a genetically distinct group. In centenarians, the EC is relatively mildly affected in terms of neuron loss even in patients with AD, and the distribution of NFT and SP lesions in hippocampus and neocortex differs from that in younger individuals [J. J. Hauw et al., Rev. Neurol. 142, 107 (1986); T. Mizutani and H. Shimada, J. Neurol. Sci. 108, 168 (1992); P. Delaère, Y. He, G. Fayet, C. Duyckaerts, J. J. Hauw, Neurobiol. Aging 14, 191 (1993); P. Giannakopoulos, P. R. Hof, M. Surini, J. P. Michel, C. Bouras, Acta Neuropathol. 85, 602 (1993); P. Giannakopoulos et al., Dementia 5, 348 (1994); G. W. Rebeck et al., Neurology 44, 1513 (1994); P. Giannakopoulos et al., Arch. Neurol. 52, 1150 (1995); P. Giannakopoulos, P. R. Hof, C. Bouras, Lancet 346, 1486 (1995); K. Ritchie and D. Kildea, ibid., p. 931; E. Sobel et al., Neurology 45, 903 (1995); T. Asada et al., J. Am. Geriatr. Soc. 44, 151 (1996); N. T. Lautenschlager et al., Neurology 46, 641 (1996)].
67. In this context, epidemiologic, clinical, and neuropathologic studies have shown that the characteristics of brain aging in very old individuals differ considerably from those in patients younger than 90 years. The prevalence of dementia is much lower among very old individuals, and it has been suggested that the "oldest-old" population may in fact represent a genetically distinct group. In centenarians, the EC is relatively mildly affected in terms of neuron loss even in patients with AD, and the distribution of NFT and SP lesions in hippocampus and neocortex differs from that in younger individuals [J. J. Hauw et al., Rev. Neurol. 142, 107 (1986); T. Mizutani and H. Shimada, J. Neurol. Sci. 108, 168 (1992); P. Delaère, Y. He, G. Fayet, C. Duyckaerts, J. J. Hauw, Neurobiol. Aging 14, 191 (1993); P. Giannakopoulos, P. R. Hof, M. Surini, J. P. Michel, C. Bouras, Acta Neuropathol. 85, 602 (1993); P. Giannakopoulos et al., Dementia 5, 348 (1994); G. W. Rebeck et al., Neurology 44, 1513 (1994); P. Giannakopoulos et al., Arch. Neurol. 52, 1150 (1995); P. Giannakopoulos, P. R. Hof, C. Bouras, Lancet 346, 1486 (1995); K. Ritchie and D. Kildea, ibid., p. 931; E. Sobel et al., Neurology 45, 903 (1995); T. Asada et al., J. Am. Geriatr. Soc. 44, 151 (1996); N. T. Lautenschlager et al., Neurology 46, 641 (1996)].
68. In this context, epidemiologic, clinical, and neuropathologic studies have shown that the characteristics of brain aging in very old individuals differ considerably from those in patients younger than 90 years. The prevalence of dementia is much lower among very old individuals, and it has been suggested that the "oldest-old" population may in fact represent a genetically distinct group. In centenarians, the EC is relatively mildly affected in terms of neuron loss even in patients with AD, and the distribution of NFT and SP lesions in hippocampus and neocortex differs from that in younger individuals [J. J. Hauw et al., Rev. Neurol. 142, 107 (1986); T. Mizutani and H. Shimada, J. Neurol. Sci. 108, 168 (1992); P. Delaère, Y. He, G. Fayet, C. Duyckaerts, J. J. Hauw, Neurobiol. Aging 14, 191 (1993); P. Giannakopoulos, P. R. Hof, M. Surini, J. P. Michel, C. Bouras, Acta Neuropathol. 85, 602 (1993); P. Giannakopoulos et al., Dementia 5, 348 (1994); G. W. Rebeck et al., Neurology 44, 1513 (1994); P. Giannakopoulos et al., Arch. Neurol. 52, 1150 (1995); P. Giannakopoulos, P. R. Hof, C. Bouras, Lancet 346, 1486 (1995); K. Ritchie and D. Kildea, ibid., p. 931; E. Sobel et al., Neurology 45, 903 (1995); T. Asada et al., J. Am. Geriatr. Soc. 44, 151 (1996); N. T. Lautenschlager et al., Neurology 46, 641 (1996)].
69. In this context, epidemiologic, clinical, and neuropathologic studies have shown that the characteristics of brain aging in very old individuals differ considerably from those in patients younger than 90 years. The prevalence of dementia is much lower among very old individuals, and it has been suggested that the "oldest-old" population may in fact represent a genetically distinct group. In centenarians, the EC is relatively mildly affected in terms of neuron loss even in patients with AD, and the distribution of NFT and SP lesions in hippocampus and neocortex differs from that in younger individuals [J. J. Hauw et al., Rev. Neurol. 142, 107 (1986); T. Mizutani and H. Shimada, J. Neurol. Sci. 108, 168 (1992); P. Delaère, Y. He, G. Fayet, C. Duyckaerts, J. J. Hauw, Neurobiol. Aging 14, 191 (1993); P. Giannakopoulos, P. R. Hof, M. Surini, J. P. Michel, C. Bouras, Acta Neuropathol. 85, 602 (1993); P. Giannakopoulos et al., Dementia 5, 348 (1994); G. W. Rebeck et al., Neurology 44, 1513 (1994); P. Giannakopoulos et al., Arch. Neurol. 52, 1150 (1995); P. Giannakopoulos, P. R. Hof, C. Bouras, Lancet 346, 1486 (1995); K. Ritchie and D. Kildea, ibid., p. 931; E. Sobel et al., Neurology 45, 903 (1995); T. Asada et al., J. Am. Geriatr. Soc. 44, 151 (1996); N. T. Lautenschlager et al., Neurology 46, 641 (1996)].
70. In this context, epidemiologic, clinical, and neuropathologic studies have shown that the characteristics of brain aging in very old individuals differ considerably from those in patients younger than 90 years. The prevalence of dementia is much lower among very old individuals, and it has been suggested that the "oldest-old" population may in fact represent a genetically distinct group. In centenarians, the EC is relatively mildly affected in terms of neuron loss even in patients with AD, and the distribution of NFT and SP lesions in hippocampus and neocortex differs from that in younger individuals [J. J. Hauw et al., Rev. Neurol. 142, 107 (1986); T. Mizutani and H. Shimada, J. Neurol. Sci. 108, 168 (1992); P. Delaère, Y. He, G. Fayet, C. Duyckaerts, J. J. Hauw, Neurobiol. Aging 14, 191 (1993); P. Giannakopoulos, P. R. Hof, M. Surini, J. P. Michel, C. Bouras, Acta Neuropathol. 85, 602 (1993); P. Giannakopoulos et al., Dementia 5, 348 (1994); G. W. Rebeck et al., Neurology 44, 1513 (1994); P. Giannakopoulos et al., Arch. Neurol. 52, 1150 (1995); P. Giannakopoulos, P. R. Hof, C. Bouras, Lancet 346, 1486 (1995); K. Ritchie and D. Kildea, ibid., p. 931; E. Sobel et al., Neurology 45, 903 (1995); T. Asada et al., J. Am. Geriatr. Soc. 44, 151 (1996); N. T. Lautenschlager et al., Neurology 46, 641 (1996)].
71. In this context, epidemiologic, clinical, and neuropathologic studies have shown that the characteristics of brain aging in very old individuals differ considerably from those in patients younger than 90 years. The prevalence of dementia is much lower among very old individuals, and it has been suggested that the "oldest-old" population may in fact represent a genetically distinct group. In centenarians, the EC is relatively mildly affected in terms of neuron loss even in patients with AD, and the distribution of NFT and SP lesions in hippocampus and neocortex differs from that in younger individuals [J. J. Hauw et al., Rev. Neurol. 142, 107 (1986); T. Mizutani and H. Shimada, J. Neurol. Sci. 108, 168 (1992); P. Delaère, Y. He, G. Fayet, C. Duyckaerts, J. J. Hauw, Neurobiol. Aging 14, 191 (1993); P. Giannakopoulos, P. R. Hof, M. Surini, J. P. Michel, C. Bouras, Acta Neuropathol. 85, 602 (1993); P. Giannakopoulos et al., Dementia 5, 348 (1994); G. W. Rebeck et al., Neurology 44, 1513 (1994); P. Giannakopoulos et al., Arch. Neurol. 52, 1150 (1995); P. Giannakopoulos, P. R. Hof, C. Bouras, Lancet 346, 1486 (1995); K. Ritchie and D. Kildea, ibid., p. 931; E. Sobel et al., Neurology 45, 903 (1995); T. Asada et al., J. Am. Geriatr. Soc. 44, 151 (1996); N. T. Lautenschlager et al., Neurology 46, 641 (1996)].
72. In this context, epidemiologic, clinical, and neuropathologic studies have shown that the characteristics of brain aging in very old individuals differ considerably from those in patients younger than 90 years. The prevalence of dementia is much lower among very old individuals, and it has been suggested that the "oldest-old" population may in fact represent a genetically distinct group. In centenarians, the EC is relatively mildly affected in terms of neuron loss even in patients with AD, and the distribution of NFT and SP lesions in hippocampus and neocortex differs from that in younger individuals [J. J. Hauw et al., Rev. Neurol. 142, 107 (1986); T. Mizutani and H. Shimada, J. Neurol. Sci. 108, 168 (1992); P. Delaère, Y. He, G. Fayet, C. Duyckaerts, J. J. Hauw, Neurobiol. Aging 14, 191 (1993); P. Giannakopoulos, P. R. Hof, M. Surini, J. P. Michel, C. Bouras, Acta Neuropathol. 85, 602 (1993); P. Giannakopoulos et al., Dementia 5, 348 (1994); G. W. Rebeck et al., Neurology 44, 1513 (1994); P. Giannakopoulos et al., Arch. Neurol. 52, 1150 (1995); P. Giannakopoulos, P. R. Hof, C. Bouras, Lancet 346, 1486 (1995); K. Ritchie and D. Kildea, ibid., p. 931; E. Sobel et al., Neurology 45, 903 (1995); T. Asada et al., J. Am. Geriatr. Soc. 44, 151 (1996); N. T. Lautenschlager et al., Neurology 46, 641 (1996)].
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186. We thank C. A. Barnes, C. Bouras, A. H. Gazzaley, P. Giannakopoulos, C. V. Mobbs, E. A. Nimchinsky, P. R. Rapp, and J. C. Vickers for their crucial contributions and advice, and W. G. M. Janssen, A. P. Leonard, and R. S. Woolley for expert technical assistance. Research in our laboratory was supported by NIH grants AG05138 and AG06647, the Human Brain Project MHDA52145, the Charles A. Dana Foundation, and the Brookdale Foundation.