The peripheral nervous system and the central nervous system (CNS) are comprised of assemblies of neurons that communicate via electrical and chemical signals. Different disease processes selectively affect specific populations of neurons and/or specific cell functions (i.e., “selective vulnerability” of neurons is a principal determinant of phenotypes of disease). New cellular and molecular biological approaches have begun to clarify some of the mechanisms of selective cell injury in human diseases and their animal models. Following a brief review of the normal biology of nerve cells, we use illustrations drawn from studies of experimental and human diseases to discuss the mechanisms of structural/chemical abnormalities that occur in a variety of neuronal disorders.
1. Armstrong DM, Bruce G, Hersh LB, and Terry RD (1986). Choline acetyltransferase immunoreactivity in ncuritic plaques of Alzheimer brain.Neurosci. Lett.71: 229–234.
2.
2. Armstrong DM, LeRoy S, Shields D, and Terry RD (1985). Somatostatin-like immunoreactivity within neuritic plaques.Drain Res.338: 71–79.
3.
3. Bahmanyar S, Higgins GA, Goldgaber D, Lewis DA, Morrison JH, Wilson MC, Shankar SK, and Gajdusek DC (1987). Localization of amyloid & protein messenger RNA in brains from patients with Alzheimer's disease.Science237: 77–79.
4.
4. Ball MJ (1977). Neuronal loss, neurofibrillary tangles and granulovacuolar degeneration in the hippocampus with ageing and dementia. A qualitative study.Acta Neuropathol. (Deri.)37: 111–118.
5.
5. Beal MF, Mazurek MF, Tran VT, Chattha G, Bird ED, and Martin JB (1985). Reduced numbers of somatostatin receptors in the cerebral cortex in Alzheimer's disease.Science229: 289–291.
6.
6. Bizzi A, Crane RC, Autilio-Gambetti L, and Gambetti P (1984). Aluminum effect on slow axonal transport: A novel impairment of neurofilament transport.J. Neurosci.4: 722–731.
7.
7. Bodian D (1949). Histopathologic basis of clinical findings in poliomyelitis.Am. J. Med.6: 563–578.
8.
8. Bowen DM, Smith CB, White P, and Davison AN (1976). Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and other abiotrophies.Drain99: 459–496.
9.
9. Brion JP, van den Bosch de Aguilar P, and Flament-Durand J (1985). Senile dementia of the Alzheimer type: Morphological and immunocytochemical studies. In: Senile Dementia of the Alzheimer Type, J Traber and WH Gispen (eds). Springer-Verlag, Berlin, pp. 164–174.
10.
10. Burns RS, Chiueh CC, Markey SP, Ebert MH, Ja-cobowitz DM, and Kopin IJ (1983). A primate model of parkinsonism: Selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyI-4-phenyl-1,2,3,6-tet-rahydropyridine.Proc. Natl. Acad. Sci. USA80: 4546–4550.
11.
11. Calne DB and Stoessl AJ (1986). Transmitter receptor alterations in Parkinson's disease. In: Parkinson's Disease. Advances in Neurology, Vol. 45, MD Yahr and KJ Bergmann (eds). Raven Press, New York, pp. 45–49.
12.
12. Carpenter S (1968). Proximal axonal enlargement in motor neuron disease.Neurology18: 841–851.
13.
13. Carroll PT, Price DL, Griffin JW, and Morris J (1978). Tetanus toxin: immunocytochemical evidence for retrograde transport.Neurosci. Lett.8:335–339.
14.
14. Clark AW, Griffin JW, and Price DL (1980). The axonal pathology in chronic IDPN intoxication.J. Neuropathol. Exp. Neurol.39: 42–55.
15.
15. Cohen ML, Golde TE, Usiak MF, Younkin LH, and Younkin SG (1988). In situ hybridization of nucleus basalis neurons shows increased β-amyloid mRNA in Alzheimer disease.Proc. Natl. Acad. Sci. USA85: 1227–1231.
16.
16. Cork LC, Altschuler RJ, Bruha PJ, Morris JM, Lloyd DG, Loats HL, Griffin JW, and Price DL (1989). Changes in neuronal size and neurotransmitter marker in Hereditary Canine Spinal Muscular Atrophy.Lab. Invest.16: 68–76.
17.
17. Cork LC, Griffin JW, Choy C, Padula CA, and Price DL (1982). Pathology of motor neurons in accelerated hereditary canine spinal muscular atrophy.Lab. Invest.46: 89–99.
19. Cork LC, Sternberger NH, Stemberger LA, Casanova MF, Struble RG, and Price DL (1986). Phos-phorylated neurofilament antigens in neurofibrillary tangles in Alzheimer's disease.J. Neuropathol. Exp. Neurol.45: 56–64.
20.
20. Cork LC, Struble RG, Gold BG, DiCarlo C, Fahne-stock KE, Griffin JW, and Price DL (1989). Changes in the size of motor axons in hereditary canine spinal muscular atrophy.Lab. Invest.61: 333–342.
21.
21. Davies P, Katzman R, and Terry RD (1980). Reduced somatostatin-like immunoreactivity in cerebral cortex from cases of Alzheimer disease and Alzheimer senile dementia.Nature288: 279–280.
22.
22. De Souza EB, Whitehouse PJ, Kuhar MJ, Price DL, and Vale WW (1986). Reciprocal changes in corti-cotropin-releasing factor (CRF)-like immunoreactivity and CRF receptors in cerebral cortex of Alzheimer's disease.Nature319: 593–595.
23.
23. Dyrks T, Weidemann A, Multhaup G, Salbaum JM, Lemaire H-G, Kang J, Müller-Hill B, Masters CL, and Beyreuther K (1988). Identification, transmembrane orientation and biogenesis of the amyloid A4 precursor of Alzheimer's disease.EMBO J.7: 949–957.
24.
24. Finn CW Jr, Silver RP, Habig WH, Hardegree MC, Zon G, and Garon CF (1984). The structural gene for tetanus neurotoxin is on a plasmid.Science224: 881–884.
25.
25. Forno LS (1986). The Lewy body in Parkinson's disease. In: Parkinson's Disease. Advances in Neurology, Vol. 45, MD Yahr and KJ Bergmann (eds). Raven Press, New York, pp. 35–43.
26.
26. Francis PT, Palmer AM, Sims NR, Bowen DM, Davison AN, Esiri MM, Neary D, Snowden JS, and Wilcock GK (1985). Neurochemical studies of early-onset Alzheimer's disease. Possible influence on treatment.N. Engl. J. Med.313: 7–11.
27.
27. Goedert M, Wischik CM, Crowther RA, Walker JE, and Klug A (1988). Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: Identification as the microtubule-associated protein tau.Proc. Natl. Acad. Sci. USA85: 4051–4055.
28.
28. Goldgabcr D, Lcrman MI, McBride OW, Saffiotti U, and Gajdusek DC (1987). Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease.Science235: 877–880.
29.
29. Goldman JE, Yen S-H, Chiu F-C, and Peress NS (1983). Lewy bodies of Parkinson's disease contain neurofilament antigens.Science221: 1082–1084.
30.
30. Goldman JE and Yen S-H (1986). Cytoskeletal protein abnormalities in neurodegenerative diseases.Ann. Neurol.19: 209–223.
31.
31. Griffin JW, Cork LC, Hoffman PN, and Price DL (1984). Experimental models of motor neuron degeneration. In: Peripheral Neuropathy, Vol. I, PJ Dyck, PK. Thomas, EH Lambert, and R Bunge (eds). W. B. Saunders, Philadelphia, pp. 621–635.
32.
32. Griffin JW, Fahnestock KE, Price DL, and Cork LC (1983). Cytoskeletal disorganization induced by local application of β,β'-iminodipropionitrile and 2,5-hexanedione.Ann. Neurol.14: 55–61.
33.
33. Griffin JW, Fahnestock KE, Price DL, and Hoffman PN (1983). Microtubule-neurofilament segregation produced by β,β'-iminodipropionitrile: Evidence for the association of fast axonal transport with microtubules.J. Neurosci.3: 557–566.
34.
34. Griffin JW, Hoffman PN, Clark AW, Carroll PT, and Price DL (1978). Slow axonal transport of neurofilament proteins: Impairment by β,β'-iminodipropionitrile administration.Science202: 633–635.
35.
35. Griffin JW, Price DL, Drachman DB, and Morris J (1981). Incorporation of axonally transported glycoproteins into axolemma during nerve regeneration.J. Cell Biol.88: 205–214.
36.
36. Griffin JW, Price DL, Engel WK, and Drachman DB (1977). The pathogenesis of reactive axonal swellings: Role of axonal transport.J. Neuropathol. Exp. Neurol.36: 214–227.
37.
37. Griffin JW, Price DL, and Hoffman PN (1983). Neurotoxic probes of the axonal cytoskeleton.Trends Neurosci.6: 490–495.
38.
38. Grundke-Iqbal I, Iqbal K, Quinlan M, Tung Y-C, Zaidi MS, and Wisnicwski HM (1986). Microtubule-associated protein tau. A component of Alzheimer paired helical filaments.J. Biol. Chem.261: 6084–6089.
39.
39. Higgins GA, Lewis DA, Bahmanyar S, Goldgaber D, Gajdusek DC, Young WG, Morrison JH, and Wilson MC (1988). Differential regulation of amy-Ioid-β-protein mRNA expression within hippocam-pal neuronal subpopulations in Alzheimer disease.Proc. Natl. Acad. Sci. USA85: 1297–1301.
40.
40. Hoffman PN, Cleveland DW, Griffin JW, Landes PW, Cowan NJ, and Price DL (1987). Neurofilament gene expression: A major determinant of axonal caliber.Proc. Natl. Acad. Sci. USA84: 3472–3476.
41.
41. Hoffman PN, Griffin JW, and Price DL (1984). Control of axonal caliber by neurofilament transport.J. Cell Biol.99: 705–714.
42.
42. Hoffman PN, Thompson GW, Griffin JW, and Price DL (1985). Changes in neurofilament transport coincide temporally with alterations in the caliber of axons in regenerating motor fibers.J. Cell Biol.101: 1332–1340.
43.
43. Hornykiewicz O and Kish SJ (1986). Biochemical pathophysiology of Parkinson's disease. In: Parkinson's Disease. Advances in Neurology, Vol. 45, MD Yahr and KJ Bergmann (eds). Raven Press, New York, pp. 19–34.
44.
44. Hughes JT (1982). Pathology of amyotrophic lateral sclerosis. In: Human Motor Neuron Diseases. Advances in Neurology, Vol. 36, LP Rowland (ed). Raven Press, New York, pp. 61–74.
45.
45. Hyman BT, Van Hoesen GW, Kromer LJ, and Da-masio AR (1986). Perforant pathway changes and the memory impairment of Alzheimer's disease.Ann. Neurol.20: 472–481.
46.
46. Javitch JA, D'Amato RJ, Strittmatter SM, and Snyder SH (1985). Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6, tetrahydropyridine: Uptake of the metabolite N-methyl-4-phenylpyri-dine by dopamine neurons explains selective toxicity.Proc. Natl. Acad. Sci. USA82: 2173–2177.
47.
47. Jellinger K (1986). Overview of morphological changes in Parkinson's disease. In: Parkinson's Disease. Advances in Neurology, Vol. 45, MD Yahr and KJ Bergmann (eds). Raven Press, New York, pp. 1–18.
48.
48. Joachim CL, Morris JH, Selkoe DJ, and Kosik KS (1987). Tau epitopes are incorporated into a range of lesions in Alzheimer's disease.J. Neuropathol. Exp. Neurol.46: 611–622.
49.
49. Johnson RT and Price DL (1980). Chronic neurological diseases: Their societal burdens and potential solutions.J. Chron. Dis.33: 129–133.
50.
50. Johnson RT (1982). Viral Infections of the Nervous System. Raven Press, New York.
51.
51. Kang J, Lemaire H-G, Unterbeck A, Salbaum JM, Masters CL, Grzeschik K-H, Multhaup G, Beyreu-ther K, and Müller-Hill B (1987). The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor.Nature325: 733–736.
52.
52. Kao I, Drachman DB, and Price DL (1976). Botulinum toxin: Mechanism of presynaptic blockade.Science193: 1256–1258.
53.
53. Kellar KJ, Whitehouse PJ, Martino-Barrows AM, Marcus K, and Price DL (1987). Muscarinic and nicotinic cholinergic binding sites in Alzheimer's disease cerebral cortex.Brain Res.436: 62–68.
54.
54. Kemper T (1984). Neuroanatomical and neuro-pathological changes in normal aging and in dementia. In: Clinical Neurology of Aging, ML Albert (ed). Oxford University Press, New York, pp. 9–52.
55.
55. Kidd M (1963). Paired helical filaments in electron-microscopy of Alzheimer's disease.Nature197: 192–193.
56.
56. Kitaguchi N, Takahashi Y, Tokushima Y, Shiojiri S, and Ito H (1988). Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity.Nature331: 530–532.
57.
57. Kitt CA, Cork LC, Eidelberg E, Joh TH, and Price DL (1986). Injury of nigral neurons exposed to 1-methyl-4-phenyl-1,2,3,6, tetrahydropyridine: A tyrosine hydroxylase immunocytochemical study in monkey.Neuroscience17: 1089–1103.
58.
58. Kitt CA, Price DL, Struble RG, Cork LC, Wainer BH, Becher MW, and Mobley WC (1984). Evidence for cholinergic neurites in senile plaques.Science226: 1443–1445.
59.
59. Kitt CA, Struble RG, Cork LC, Mobley WC, Walker LC, Joh TH, and Price DL (1985). Catecholaminer-gic neurites in senile plaques in prefrontal cortex of aged nonhuman primates.Neuroscience16: 691–699.
60.
60. Koliatsos VE, Applegate MD, Kitt CA, Walker LC, DeLong MR, and Price DL (1989). Aberrant phosphorylation of neurofilaments accompanies transmitter-related changes in rat septal neurons following transection of the fimbria-fornix.Brain Res.482: 205–218.
61.
61. Koo EH, Goldgaber D, Sisodia SS, Applegate MD, Gajdusek DC, and Price DL (1988). Studies of β-amyloid precursor gene expression in brains of aged monkeys.Soc. Neurosci. Abstr.14: 637.
62.
62. Koo EH, Hoffman PN, and Price DL (1988). Levels of neurotransmitter and cytoskeletal mRNAs during nerve regeneration in sympathetic ganglia.Brain Res.449: 361–363.
63.
63. Kopin IJ and Markey SP (1988). MPTP toxicity: Implications for research in Parkinson's disease.Annu. Rev. Neurosci.11: 81–96.
64.
64. Kosik KS (1989). Minireview: The molecular and cellular pathology of Alzheimer neurofibrillary lesions.J. Gerontol. Biol. Sci.44: B55–B58.
65.
65. Langston JW, Forno LS, Rebert CS, and Irwin I (1984). Selective nigral toxicity after systemic administration of 1-methyl-4-phenyl-1,2,5,6-tetra-hydropyridine (MPTP) in the squirrel monkey.Brain Res.292: 390–394.
66.
66. Langston JW, Irwin I, Langston EB, and Forno LS (1984). 1-Methyl-4-phenylpyridinium ion (MPP+): Identification of a metabolite of MPTP, a toxin selective to the substantia nigra.Neurosci. Lett.48: 87–92.
67.
67. Lewis DA, Campbell MJ, Terry RD, and Morrison JH (1987). Laminar and regional distributions of neurofibrillary tangles and neuritic plaques in Alzheimer's disease: A quantitative study of visual and auditory cortices.J. Neurosci.7: 1799–1808.
69. Love S, Saitoh T, Quijada S, Cole GM, and Terry RD (1988). Alz-50, ubiquitin and tau immunoreac-tivity of neurofibrillary tangles, Pick bodies and Lewy bodies.J. Neuropathol. Exp. Neurol.47: 393–405.
70.
70. Martin LJ, Cork LC, Koo EH, Sisodia SS, Weidemann A, Beyreuther K, Masters C, and Price DL (1989). Localization of amyloid precursor protein (APP) in brains of young and aged monkeys.Soc. Neurosci. Abstr.15: 23.
71.
71. Masters CL, Multhaup G, Simms G, Pottgiesscr J, Martins RN, and Beyreuther K (1985). Neuronal origin of cerebral amyloid: Neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels.EMBO J.4: 2757–2763.
72.
72. Miller WC and DeLong MR (1988). Parkinsonian symptomatology. An anatomical and physiological analysis.Ann. NY. Acad. Sci.515: 287–302.
73.
73. Mori H, Kondo J, and Ihara Y (1987). Ubiquitin is a component of paired helical filaments in Alzheimer's disease.Science235: 1641–1644.
74.
74. Morrison JH, Lewis DA, Campbell MJ, Huntley GW, Benson DL, and Bouras C (1987). A monoclonal antibody to non-phosphorylated neurofilament protein marks the vulnerable cortical neurons in Alzheimer's disease.Brain Res.416: 331–336.
75.
75. Muma NA, Hoffman PN, Slunt HH, Applegate MD, Lieberburg I, and Price DL (1990). Discordant regulation of levels of mRNA coding for neurofilament protein subunits during regeneration.Exp. Neurol. (in press).
77. Palmert MR, Golde TE, Cohen ML, Kovacs DM, Tanzi RE, Gusella JF, Usiak MF, Younkin LH, and Younkin SG (1988). Amyloid protein precursor messenger RNAs: Differential expression in Alzheimer's disease.Science241: 1080–1084.
78.
78. Parsons B and Rainbow TC (1984). High-affinity binding sites for [3H]MPTP may correspond to monamine oxidase.Eur. J. Pharmacol.102: 375–377.
79.
79. Perry G, Friedman R, Shaw G, and Chau V (1987). Ubiquitin is detected in neurofibrillary tangles and senile plaque neurites of Alzheimer disease brains. Proc.Natl. Acad. Sci. USA84: 3033–3036.
80.
80. Perry G, Mulvihill P, Manetto V, Autilio-Gambetti L, and Gambetti P (1987). Immunocytochemical properties of Alzheimer straight filaments.J. Neurosci.7: 3736–3738.
81.
81. Perry G, Rizzuto N, Autilio-Gambetti L, and Gambetti P (1985). Paired helical filaments from Alzheimer disease patients contain cytoskeletal components.Proc. Natl. Acad. Sci. USA82: 3916–3920.
82.
82. Perry RH, Candy JM, Perry EK, Irving D, Blessed G, Fairbairn AF, and Tomlinson BE (1982). Extensive loss of choline acetyl transferase activity is not reflected by neuronal loss in the nucleus of Meynert in Alzheimer's disease.Neurosci. Lett.33: 311–315.
83.
83. Ponte P, Gonzalez-DeWhitt P, Schilling J, Miller J, Hsu D, Greenberg B, Davis K, Wallace. V, Lieberburg I, Fuller F, and Cordell B (1988). A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors.Nature331: 525–527.
84.
84. Powers RE, Struble RG, Casanova MF, O'Connor DT, Kitt CA, and Price DL (1988). Innervation of human hippocampus by noradrenergic systems: Normal anatomy and structural abnormalities in aging and in Alzheimer's disease.Neuroscience25: 401–417.
85.
85. Powers RE, Walker LC, DeSouza EB, Vale WW, Struble RG, Whitehouse PJ, and Price DL (1987). Immunohistochemical study of neurons containing corticotropin-releasing factor in Alzheimer's disease.Synapse1: 405–410.
86.
86. Prcsty SK, Bachevalier J, Walker LC, Struble RG, Price DL, Mishkin M, and Cork LC (1987). Age differences in recognition memory of the rhesus monkey (Macaca mulatta).Neurobiol. Aging8: 435–440.
87.
87. Price DL, Bergey GK, Griffin JW, and Stanley EF (1987). Tetanus. In: Infections and Cancer. Handbook of the Spinal Cord. Vol. 5, RA Davidoff (ed). Marcel Dekker, New York, pp. 539–558.
89. Price DL, Griffin JW, Hoffman PN, Cork LC, and Spencer PS (1984). The response of motor neurons to injury and disease. In: Peripheral Neuropathy, Vol. I, PJ Dyck, PK Thomas, EH Lambert, and R Bunge (eds). W. B. Saunders, Philadelphia, pp. 732–759.
90.
90. Price DL, Griffin JW, and Peck K (1977). Tetanus toxin: Evidence for binding at presynaptic nerve endings.Brain Res.121: 379–384.
91.
91. Price DL and Griffin JW (1977). Tetanus toxin: Retrograde axonal transport of systemically administered toxin.Neurosci. Lett.4: 61–65.
92.
92. Price DL, Griffin J, Young A, Peck K, and Stocks A (1975). Tetanus toxin: Direct evidence for retrograde intraaxonal transport.Science188: 945–947.
93.
93. Price DL, Koo EH, Sisodia SS, Martin LJ, Koliatsos VE, Muma NA, Walker LC, and Cork LC (in press). Neuronal responses to injury and aging: Lessons from animal models. Prog. Brain Res.
94.
94. Price DL, Koo EH, Sisodia SS, Martin LJ, Walker LC, Kitt CA, and Cork LC (in press). Brain abnormalities in aged monkeys: A model sharing features with Alzheimer's disease. In: Alzheimer's Disease: Epidemiology, Neuropathology, Neurochemistry, Clinics, K Maurer, P Riederer, and H Beckmann (eds). Springer-Verlag, Wien, Austria.
95.
95. Price DL, Koo EH, and Unterbeck A (1989). Cellular and molecular biology of Alzheimer's disease.BioEssays10: 69–74.
96.
96. Price DL (1986). New perspectives on Alzheimer's disease.Annu. Rev. Neurosci.9: 489–512.
97.
97. Price DL and Porter KR (1972). The response of ventral horn neurons to axonal transection.J. Cell Biol.53: 24–37.
98.
98. Price DL, Stocks A, Griffin JW, Young A, and Peck K (1976). Glycine-specific synapses in rat spinal cord: Identification by electron microscope autoradiography.J. Cell Biol.68: 389–395.
99.
99. Price DL, Whitehouse PJ, and Struble RG (1986). Cellular pathology in Alzheimer's and Parkinson's diseases.Trends Neurosci.9: 29–33.
100.
100. Redmond DE, Sladck JR Jr, Roth RH, Collier TJ, Elsworth JD, Deutch AY, and Haber S (1986). Fetal neuronal grafts in monkeys given methylphenyltet-rahydropyridinc.Lancet1: 1125–1127.
101.
101. Robakis NK, Wisniewski HM, Jenkins EC, Devine-Gage EA, Houck GE, Yau X-L, Ramakrishna N, Wolfe G, Silverman WP, and Brown WT (1987). Chromosome 21q21 sublocalisation of gene encoding beta-amyloid peptide in cerebral vessels and neuritic (senile) plaques of people with Alzheimer disease and Down syndrome.Lancet1: 384–385.
102.
102. Roberts GW, Crow TJ, and Polak JM (1985). Location of neuronal tangles in somatostatin neurones in Alzheimer's disease.Nature314: 92–94.
103.
103. Ross CA, Zweig RM, Hedreen JC, Whitehouse PJ, Steele C, Folstein MF, and Price DL (in press). Depression and cell loss in the locus coeruleus in Alzheimer's disease. Biol. Psychiatry.
104.
104. Rowland LP (1987). Motor neuron diseases and amyotrophic lateral sclerosis: Research progress.Trends Neurosci.10: 393–398.
106. Sclkoc DJ, Bell DS, Podlisny MB, Price DL, and Cork LC (1987). Conservation of brain amyloid proteins in aged mammals and humans with Alzheimer's disease.Science235: 873–877.
107.
107. Selkoe DJ (1989). Biochemistry of altered brain proteins in Alzheimer's disease.Annu. Rev. Neurosci.12: 463–490.
108.
108. Shoulson I, Fahn S, and Langston JW (1988). Symposium on the etiology, pathogenesis, and prevention of Parkinson's disease.Arch. Neurol.45: 807–811.
109.
109. Siddique T, Pcricak-Vance MA, Brooks BR, Roos RP, Hung W-Y, Antel JP, Munsat TL, Phillips K, Warner K, Speer M, Bias WB, Siddique NA, and Roses AD (1989). Linkage analysis in familial amyotrophic lateral sclerosis.Neurology39: 919–925.
110.
110. Simpson LL (1986). Molecular pharmacology of botulinum toxin and tetanus toxin.Annu. Rev. Pharmacol. Toxicol.26: 427–453.
111.
111. Stanley EF and Drachman DB (1983). Botulinum toxin blocks quantal but not non-quantal release of ACh at the neuromuscular junction.Brain Res.261: 172–175.
112.
112. Strublc RG, Cork LC, Whitehouse PJ, and Price DL (1982). Cholinergic innervation in neuritic plaques.Science216: 413–415.
113.
113. Struble RG, Hedreen JC, Cork LC, and Price DL (1984). Acetylcholinesterase activity in senile plaques of aged macaques.Neurobiol. Aging5: 191–198.
114.
114. Struble RG, Kitt CA, Walker LC, Cork LC, and Price DL (1984). Somatostatinergic neurites in senile plaques of aged non-human primates.Brain Res.324: 394–396.
115.
115. Struble RG, Powers RE, Casanova MF, Kitt CA, Brown EC, and Price DL (1987). Neuropeptidergic systems in plaques of Alzheimer's disease.J. Neuropathol. Exp. Neurol.46: 567–584.
116.
116. Struble RG, Price DL Jr, Cork LC, and Price DL (1985). Senile plaques in cortex of aged normal monkeys.Brain Res.361: 267–275.
117.
117. Tandan R and Bradley WG (1985). Amyotrophic lateral sclerosis: Part 1. Clinical features, pathology, and ethical issues in management.Ann. Neurol.18: 271–280.
118.
118. Tandan R and Bradley WG (1985). Amyotrophic lateral sclerosis: Part 2. Etiopathogenesis.Ann. Neurol.18: 419–431.
119.
119. Tanzi RE, Gusella JF, Watkins PC, Bruns GAP, St George-Hyslop P, Van Keuren ML, Patterson D, Pagan S, Kurnit DM, and Neve RL (1987). Amyloid β protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus.Science235: 880–884.
120.
120. Tanzi RE, McCIatchey AI, Lampert ED, Villa-Komaroff L, Gusella JF, and Neve RL (1988). Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease.Nature331: 528–530.
121.
121. Terry RD (1963). The fine structure of neurofibrillary tangles in Alzheimer's disease.J. Ncuropalhol. Exp. Neurol.22: 629–642.
122.
122. Terry RD, Peck A, DeTeresa R, Schechter R, and Horoupian DS (1981). Some morphomctric aspects of the brain in senile dementia of the Alzheimer type.Ann. Neurol.10: 184–192.
123.
123. Thesleff S (1984). Transmitter release in botulinum-poisoned muscles.J. Physiol.79: 192–195.
124.
124. Troncoso JC, Hoffman PN, Griffin JW, Hess-Kozlow KM, and Price DL (1985). Aluminum intoxication: A disorder of neurofilament transport in motor neurons.Brain Res.342: 172–175.
125.
125. Troncoso JC, Price DL, Griffin JW, and Parhad IM (1982). Neurofibrillary axonal pathology in aluminum intoxication.Ann. Neurol.12: 278–283.
126.
126. Troncoso JC, Sternberger NH, Sternberger LA, Hoffman PN, and Price DL (1986). Immunocyto-chemical studies of neurofilament antigens in the neurofibrillary pathology induced by aluminum.Brain Res.364: 295–300.
127.
127. van Heyningen S (1980). Tetanus toxin.Pharmacol. Ther.11: 141–147.
128.
128. Wagster MV, Whitehouse PJ, Walker LCKellar KJ, and Price DL (in press). Laminar organization and age-related loss of cholinergic receptors in temporal neocortex of rhesus monkey. J. Neurosci.
129.
129. Walker LC, Kitt CA, Cork LC, Struble RG, Dellovade TL, and Price DL (1988). Multiple transmitter systems contribute neurites to individual senile plaques.J. Neuropathol. Exp. Neurol.47: 138–144
130.
130. Walker LC, Kitt CA, Schwam E, Buckwald B, Garcia F, Sepinwall J, and Price DL (1987). Senile plaques in aged squirrel monkeys.Neurobiol. Aging8: 291–296.
131.
131. Walker LC, Kitt CA, Struble RG, Schmechel DE, Oertel WH, Cork LC, and Price DL (1985). Glutamic acid decarboxylase-like immunoreactive neurites in senile plaques.Neurosci. Lett.59: 165–169.
132.
132. Walker LC, Kitt CA, Struble RG, Wagster M V, Price DL, and Cork LC (1988). The neural basis of memory decline in aged monkeys.Neurobiol. Aging9: 657–666.
133.
133. Weidemann A, Konig G, Bunke D, Fischer P, Salbaum JM, Masters CL, and Beyrcuther K (1989). Identification, biogenesis, and localization of precursors of Alzheimer's disease A4 amyloid protein.Cell57: 115–126.
135. Wenk GL, Pierce DJ, Struble RG, Price DL, and Cork LC (1989). Age-related changes in multiple neurotransmitter systems in the monkey brain.Neurobiol. Aging10: 11–19.
137. Whitehouse PJ, Price DL, Struble RG, Clark AW, Coyle JT, and DeLong MR (1982). Alzheimer's disease and senile dementia: Loss of neurons in the basal forebrain.Science215: 1237–1239.
139. Wischik CM, Novak M, Edwards PC, Klug A, Tichelaar W, and Crowther RA (1988). Structural characterization of the core of the paired helical filament of Alzheimer disease.Proc. Natl. Acad. Sci. USA85: 4884–4888.
140.
140. Wischik CM, Novak M, Thogersen HC, Edwards PC, Runswick MJ, Jakes R, Walker JE, Milstein C, Roth M, and Klug A (1988). Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease.Proc. Natl. Acad. Sci. USA85: 4506–4510.
141.
141. Wisniewski HM, Merz PA, and Iqbal K (1984). Ultrastructure of paired helical filaments of Alzheimer's neurofibrillary tangle.J. Neuropalhol. Exp. Neurol.43: 643–656.
142.
142. Wolozin B and Davies P (1987). Alzheimer-related neuronal protein A68: Specificity and distribution.Ann. Neurol.22: 521–526.
143.
143. Wong CW, Quaranta V, and Glenner GG (1985). Neuritic plaques and cerebrovascular amyloid in Alzheimer disease arc antigenically related.Proc. Natl. Acad. Sci. USA82: 8729–8732.
144.
144. Zweig RM, Ross CA, Hedreen JC, Steele C, Cardillo JE, Whitehouse PJ, Folstein MF, and Price DL (1988). The neuropathology of aminergic nuclei in Alzheimer's disease.Ann. Neurol.24: 233–242.
