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Tacrine, a Drug with Therapeutic Potential for Dementia: Post-Mortem Biochemical Evidence

Published online by Cambridge University Press:  18 September 2015

Paul T. Francis  and
David M. Bowen
Paul T. Francis*
Affiliation:
Department of Neurochemistry, Institute of Neurology, The National Hospital for Nervous Diseases (Queen Square), University of London, GB
David M. Bowen
Affiliation:
Department of Neurochemistry, Institute of Neurology, The National Hospital for Nervous Diseases (Queen Square), University of London, GB
*
Institute of Neurology, 1 Wakefield Street, London WC1N 1PJ, UK
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Abstract:

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A review of biochemical findings is presented which support the idea that Alzheimer's disease represents a condition for which tetrahydroaminoacridine (tacrine) may have a beneficial effect. There is evidence that clinical and histopathologic hallmarks of the disease relate to cholinergic and serotonergic dysfunction, with less obvious abnormalities in other neurotransmitters (aspartate, dopamine, gamma-aminobutyrate, glutamate, noradrenaline and somatostatin). Clincially relevant concentrations of tacrine may ameliorate the above presynaptic deficits without producing harmful (neurotoxic) effects of aspartate and glutamate. The disease seems to be associated with an early and clinically relevant degeneration of some neurons with cortical perikarya that release these amino acid transmitters. Studies are now required on the effect of tacrine on postulated harmful peptide-bond hydrolase activity within and around such cells.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 16 , Issue S4 , November 1989 , pp. 504 - 510
Copyright
Copyright © Canadian Neurological Sciences Federation 1989

References

REFERENCES

1.Steele, JE, Palmer, AM, Lowe, SL, et al. The influence of tetrahydro-9-aminoacridine on excitatory amino acid neurotransmission in vivo and in vitro. Br J Pharmacol; 1989; 96: 3530.Google Scholar
2.Mattson, MP. Neurotransmitters in the regulation of neuronal cytoarchitecture. Brain Res Rev 1988; 13: 179–212.CrossRefGoogle Scholar
3.Summers, WK, Majouski, LV, Marsh, GM, et al. Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer type. New Eng J Med; 1986; 315: 1241–124.CrossRefGoogle ScholarPubMed
4.Robinson, TN, De Souza, RJ, Cross, AJ, et al. The mechanism of tetrahydroaminoacridine (THA)-evoked release of endogenous 5-hydroxytryptamine and dopamine from rat brain prisms. Brit J Pharmacol(in press).Google Scholar
5.Spokes, EGS. An analysis of factors influencing measurements of dopamine, noradrenaline, glutamate decarboxylase, and choline acetyltransferase in human postmortem brain. Brain 1979; 102: 333–346.CrossRefGoogle Scholar
6.Cheetham, SC, Crompton, MR, Katona, LE, et al. Brain GABAA/benzodiazepine binding sites and glutamic decarboxylase activity in depressed suicide victims. Brian Res; 1988; 460: 114–123.CrossRefGoogle ScholarPubMed
7.Lowe, SL, Francis, PT, Procter, AW, et al. Gamma-aminobutyric acid concentration in brain tissue at two stages of Alzheimer’s disease. Brain; 1988; 111: 785–799.CrossRefGoogle ScholarPubMed
8.Palmer, AM, Lowe, SL, Francis, PT, et al. Are postmortem biochemical studies of human brain worthwhile?. Biochem Soc Trans; 1988; 16: 472–475.CrossRefGoogle ScholarPubMed
9.Procter, AW, Palmer, AM, Francis, PT, et al. Evidence of glutamatergic denervation and possible abnormal metabolism in Alzheimer’s disease. J Neurochem; 1988; 50: 790–802.CrossRefGoogle ScholarPubMed
10.Nicholls, DG, Sihara, TS, Sanchez-Prieto, J. Calcium-dependent and-independent release of glutamate from synaptosomes monitored by continuous fluorometry. J Neurochem; 1987; 49: 50–57.CrossRefGoogle ScholarPubMed
11.Procter, AW, Lowe, SL, Palmer, AM, et al. Topographical distribution of neurochemical changes in Alzheimer’s disease. J Neurol Sci; 1988; 84: 125–140.CrossRefGoogle ScholarPubMed
12.Bowen, DM, Davison, AN. Biochemical studies of nerve cells and energy metabolism in Alzheimer’s disease. Brit Med Bull; 1986; 42: 75–80.CrossRefGoogle ScholarPubMed
13.Palmer, AM, Stratmann, GC, Procter, AW, et al. Possible neurotransmitter basis of behavioural changes in Alzheimer’s disease. Ann Neurol; 1988; 23: 616–620.CrossRefGoogle ScholarPubMed
14.Bowen, DM, White, P, Spillane, JA, et al. Accelerated aging or selective neuronal loss as an important cause of dementia?. Lancet; 1979; i: 11–14.Google ScholarPubMed
15.Arregui, A, Perry, EK, Rossor, M, et al. Angiotensin converting enzyme in Alzheimer’s disease: Increased activity in caudate nucleus and cortical areas. J Neurochem; 1982; 38 : 1490–1492.CrossRefGoogle ScholarPubMed
16.Bowen, DM, Sims, NR, Lee, KAD, et al. Acetylcholine synthesis and glucose oxidation are preserved in human brain obtained shortly after death. Neurosci Lett; 1982; 31 : 195–199.CrossRefGoogle ScholarPubMed
17.Dodd, PR, Hambley, JW, Cowburn, RF, et al. A comparison of methodologies for the study of functional transmitter neuro-chemistry in human brain. J Neurochem; 1988; 50 : 1333–1345.CrossRefGoogle Scholar
18.Palmer, AM, Francis, PT, Bowen, DM, et al. Catecholaminergic neurons assessed antemortem in Alzheimer’s disease. Brain Res; 1987; 414 : 365–37.CrossRefGoogle ScholarPubMed
19.Procter, AW, Wong, EHF, Stratmann, GC, et al. Reduced glycine stimulation of [3H]MK801 binding in Alzheimer’s disease. J Neurochem; 1989; 53 : 698–704.CrossRefGoogle ScholarPubMed
20.Palmer, AM, Procter, AW, Stratmann, GC, et al. Excitatory amino acid-releasing and cholinergic neurons in Alzheimer’s disease. Neurosci Lett; 1986; 66 : 199–204.CrossRefGoogle ScholarPubMed
21.Cross, AJ, Slater, P, Candy, JM, et al. Glutamate deficits in Alzheimer’s disease. J Neurol Neurosurg Psychiatry; 1987; 50 : 357–358.CrossRefGoogle Scholar
22.Hardy, J, Cowburn, R, et al. Region-specific loss of gluta-mate innervation in Alzheimer’s disease. Neurosci Lett; 1987; 73 : 77–80.CrossRefGoogle Scholar
23.McGeer, EG, Singh, EA, McGeer, PL. Sodium-dependent glutamate binding in senile dementia. Neurobiol Aging; 1987; 8 : 219–223.CrossRefGoogle ScholarPubMed
24.Cowburn, R, Hardy, J, Roberts, P, et al. Presynaptic glutamatergic function in Alzheimer’s disease. Brain Res; 1988; 452 : 403–407.CrossRefGoogle Scholar
25.Simpson, MDC, Royston, MC, Deakin, JFW, et al. Regional changes in [3H]D-aspartate and PH]TCP binding sites in Alzheimer’s disease brains. Brain Res; 1988; 462 : 76–82.CrossRefGoogle ScholarPubMed
26.Jones, EG. Neurotransmitters in the cerebral cortex. J Neurosurg 1986; 65: 135–153.CrossRefGoogle ScholarPubMed
27.Reinikainen, KJ, Paljarvi, L, Huuskonen, M, et al. A postmortem study of noradrenergic, serotonergic and GABAergic neurons in Alzheimer’s disease. J Neurol Sci; 1988; 84 : 101–116.CrossRefGoogle ScholarPubMed
28.Ellison, DW, Beai, MF, Mazurek, MF, et al. A postmortem study of amino-acid neurotransmitters in Alzheimer’s disease. Ann Neurol; 1986; 20 : 616–621.CrossRefGoogle ScholarPubMed
29.Hardy, J, Cowburn, R, Barton, A, et al. A disorder of cortical GABAergic innervation in Alzheimer’s disease. Ann Neurol; 1987; 73 : 192–196.Google ScholarPubMed
30.Simpson, MDC, Cross, AJ, Slater, P, et al. Loss of cortical GABA uptake sites in Alzheimer’s disease. J Neural Trans; 1988; 71 : 219–226.CrossRefGoogle ScholarPubMed
31.Jones, EG, Hendry, SHC. Expression of neuronal diversity in the central nervous system. In: Jones, EG, ed. Molecular Biology of the Human Brain. New York: Alan R. Liss Ine, 1988; 3: 3–11.Google Scholar
32.Beai, MF, Martin, JB. Neuropeptides in neurological disease. Neurol Neurosurg Psychiatry 1986; 20: 547–565.Google Scholar
33.Chan-Palay, V. Galanin hyperinnervates surviving neurons of the human basal nucleus of Meynert in dementia of Alzheimer’s and Parkinson’s disease: A hypothesis for the role of galanin in accentuating cholinergic dysfunction in dementia. J Comp Neurol 1988; 173: 543–557.CrossRefGoogle Scholar
34.Bissettee, G, Reynolds, GP, Kilts, CD, et al. Corticotropin-releasing factor-like immunoreactivity in senile dementia of the Alzheimer type. JAMA; 1985; 254 : 3067–3069.CrossRefGoogle Scholar
35.De Souza, EB, Whitehouse, PJ, Kuhar, MJ, et al. Reciprocal changes in corticotropin-releasing factor (CRF)-like immunoreactivity and CRF receptors in cerebral cortex of Alzheimer’s disease. Nature; 1986; 319 : 593–545.CrossRefGoogle ScholarPubMed
36.Beal, MF, elevens, RA, Chattha, GK, et al. Galanin-like immunoreactivity is unchanged in Alzheimer’s disease and Parkinson’s disease dementia cerebral cortex. J Neurochem; 1988; 51 : 1935–1941.CrossRefGoogle ScholarPubMed
37.Francis, PT, Bowen, DM, Lowe, SL, et al. Somatostatin content and release measured in cerebral biopsies from demented patients. J Neurol Sci; 1987; 78 : 1–16.CrossRefGoogle ScholarPubMed
38.Beal, MF, Mazurek, MF, Geetinder, KC, et al. Neuropeptide Y immunoreactivity is reduced in cerebral cortex in Alzheimer’s disease. Ann Neurol; 1986; 20 : 282–288.CrossRefGoogle ScholarPubMed
39.Vincent, SR, Johannson, U, Hokfelt, T. Neuropeptide coexistence in human neurons. Nature; 1982; 298 : 65–67.CrossRefGoogle Scholar
40.Rylett, RJ, Ball, MJ, Colhoun, EH. Evidence for high affinity choline transport in synaptosomes prepared from hippocampus of patients with Alzheimer’s disease. Brain Res; 1983; 289 : 169–175.CrossRefGoogle ScholarPubMed
41.Richter, JA, Perry, EK, Tomlinson, BE. Acetylcholine and choline levels in postmortem human tissue: Preliminary observations in Alzheimer’s disease. Life Sci; 1980; 26 : 1683–1689.CrossRefGoogle ScholarPubMed
42.Nordberg, A, Adem, A, Nilsson, L, et al. Cholinergic deficits in CNS and peripheral non-neuronal tissue in Alzheimer’s disease. In: Dowdall, MJ, Hawthorne, JN, eds. Cellular and Molecular Basis of Cholinergic Function. Chichester: Ellis Horwood, 1987: 858–868.Google Scholar
43.Arendt, T, Bigi, V. Alzheimer’s plaques and cortical cholinergic innervation. Neurology 1986; 17: 277–279.Google ScholarPubMed
44.Perry, RH, Irving, D, Blessed, G, et al. Clinically and neuropathologically distinct form of dementia in the elderly. Lancet 1989; 1: 166.CrossRefGoogle ScholarPubMed
45.Bowen, DM, Allen, SJ, Benton, JS, et al. Biochemical assessment of serotonergic and cholinergic dysfunction and cerebral atrophy in Alzheimer’s disease. J Neurochem 1983; 41: 266–272.CrossRefGoogle ScholarPubMed
46.Perry, EK, Marshall, EF, Blessed, G. Decreased imipramine binding in the brains of patients with depression. Brit J Psychiat 1983; 142: 188–192.CrossRefGoogle Scholar
47.D’Amato, RJ, Zweig, RM, Whitehouse, PJ, et al. Aminergic systems in Alzheimer’s disease and Parkinson’s disease. Ann Neurol 1987; 22: 229–236.CrossRefGoogle ScholarPubMed
48.Palmer, AM, Wilcock, GK, Esiri, MM. Monoaminergic innervation of the frontal and temporal lobes in Alzheimer’s disease. Brain Res 1987; 401: 231–238.CrossRefGoogle ScholarPubMed
49.Cross, AJ, Crow, TJ, Johnson, JA, et al. Monoamine metabolism in senile dementia of Alzheimer type. J Neurol Sci 1983; 60: 383–392.CrossRefGoogle ScholarPubMed
50.Iversen, LL, Rossor, MW, Reynolds, GP, et al. Loss of pigmented dopamine-B-hydroxylase positive cells from locus ceruleus in senile dementia of Alzheimer’s type. Neurosci Lett 1984; 34: 95–100.Google Scholar
51.Birdsall, NJM, Hulme, EC. Future directions. In: Heller-Brown, J, ed. Muscarinic Receptors. New Jersey: Humana Press (in press).Google Scholar
52.Flynn, DD, Mash, DC. Characterization of [3H]nicotine binding in human cerebral cortex: Comparison between Alzheimer’s disease and normal. J Neurochem 1986; 47: 1948–1954.CrossRefGoogle ScholarPubMed
53.Smith, CJ, Perry, EK, Perry, RH, et al. Muscarinic cholinergic receptor subtypes in hippocampus in human cognitive disorders. J Neurochem 1988; 50: 547–8546.CrossRefGoogle ScholarPubMed
54.Young, LT, Kish, SJ, Li, PP, et al. Decreased brain [3H]-inositol 1,4,5-trisphosphate binding in Alzheimer’s disease. Neurosci Lett 1988; 94: 198–202.CrossRefGoogle ScholarPubMed
55.Whitehouse, PJ, Marinu, AM, Antuono, PG, et al. Nicotine acetylcholine binding sites in Alzheimer’s disease. Brain Res 1986; 371: 146–151.CrossRefGoogle ScholarPubMed
56.Cross, AJ, Crow, TJ, Ferrier, IN, et al. The selectivity of the reduction of serotonin S2 receptors in Alzheimer-type dementia. Neurobiol Aging 1986; 7: 3–8.CrossRefGoogle ScholarPubMed
57.Middlemiss, DN, Bowen, DM, Palmer, AM. Serotonin neurons and receptors in Alzheimer’s disease. In: Briley, M, Kato, A, and Weber, M, eds. New Concepts in Alzheimer’s Disease. Pierre Fabre Monograph Series vol. 1. London: Macmillan Press, 1986: 89–102.CrossRefGoogle Scholar
58.Procter, AW, Middlemiss, DN, Bowen, DM. Selective loss of serotonin recognition sites in the parietal cortex in Alzheimer’s disease. Int J Geriat Psychiat 1988; 3: 37–44.CrossRefGoogle Scholar
59.Procter, AW, Sterling, JH, Stratmann, GC. Loss of glycine-dependent radioligand binding to the N-methyl-D-aspartate-phencyclidine receptor complex in patients with Alzheimer’s disease. Neurosci Lett 1989; 101: 62–66.CrossRefGoogle Scholar
60.Beai, MF, Mazurek, MF, Tran, VT, et al. Reduced numbers of somatostatin receptors in the cerebral cortex in Alzheimer’s disease. Science 1985; 224: 284–291.Google Scholar
61.Cross, AJ, Crow, TJ, Ferrier, IN, et al. Striatal dopamine receptors in Alzheimer-type dementia. Neurosci Lett 1984; 52: 1–6.CrossRefGoogle ScholarPubMed
62.Rinne, JO, Sako, E, Paljora, L, et al. Brain dopamine D-2 receptors in senile dementia. J Neurol Trans 1986; 65: 51–62.CrossRefGoogle ScholarPubMed
63.Palmer, AM, Hudson, PH, Lowe, SL, et al. Extracellular concentrations of aspartate and glutamate in rat neostriatum following chemical stimulation of frontal cortex. Exp Brain Res 1989; 75: 659–663.CrossRefGoogle ScholarPubMed
64.Neary, D, Snowden, JS, Bowen, DM, et al. Neuropsychological syndromes in presenile dementia due to cerebral atrophy. J Neurol Neurosurg Psychiat 1986; 49: 163–174.CrossRefGoogle ScholarPubMed
65.Neary, D, Snowden, JS, Mann, DMA, et al. Alzheimer’s disease; a correlative study. J Neurol Neurosurg Psychiatry 1986; 49: 229–237.CrossRefGoogle ScholarPubMed
66.Bowen, DM, Smith, CB, White, P, et al. Chemical pathology of the organic dementias: I Validity of biochemical measurements in human postmortem brain specimens. Brain 1977; 100: 397–426.CrossRefGoogle Scholar
67.Korey, SR, Scheinberg, L, Terry, R, et al. Studies in presenile dementia. Trans Am Neurol Assoc 1961; 86: 99–102.Google ScholarPubMed
68.Smith, CCT, Bowen, DM, Sims, NR, et al. Amino acid release from biopsy samples of temporal neocortex from patients with Alzheimer’s disease. Brain Res 1983; 264: 138–141.CrossRefGoogle ScholarPubMed
69.Spillane, JA, White, P, Goodhart, MJ, et al. Selective vulnerability of neurons in organic dementia. Nature 1977; 266: 3558–3560.CrossRefGoogle ScholarPubMed
70.Palmer, AM, Francis, PT, Benton, JS, et al. Presynaptic serotonergic dysfunction in patients with Alzheimer’s disease. J Neurochem 1987; 8–15.CrossRefGoogle ScholarPubMed
71.Sims, NR, Bowen, DM, Allen, ST, et al. Presynaptic cholinergic dysfunction in patients with dementia. J Neurochem 1983; 40: 503–509.CrossRefGoogle ScholarPubMed
72.Cotman, CW, Geddes, JW, Monahan, DT, et al. Excitatory amino acid receptors in Alzheimer’s disease. In: Davies, P, Finch, CE, eds. Molecular Neuropathology of Aging (Banbury report 27), Cold Spring Harbor Laboratory, 1987; 67–84.Google Scholar
73.Francis, PT, Palmer, AM, Sims, NR, et al. Neurochemical studies of early-onset Alzheimer’s disease: Possible influence on treatment. N Engl J Med 1985; 313: 7–11.CrossRefGoogle ScholarPubMed
74.Cutler, NR, Haxby, JV, Duara, R, et al. Clinical history, brain metabolism and neuropsychological function in Alzheimer’s disease. Ann Neurol 1985; 18: 298–309.CrossRefGoogle ScholarPubMed
75.Miller, JD, de Leon, MJ, Ferris, SH, et al. Abnormal temporal lobe response in Alzheimer’s disease during cognitive processing as measured by [11C]-2-deoxy-D-glucose and PET. J Cereb Blood Flow Metab 1987; 7: 248–251.CrossRefGoogle ScholarPubMed
76.Pearson, RCA, Esiri, MM, Hiorns, RW, et al. Anatomical correlates of the distribution of the pathological changes in the neocortex in Alzheimer’s disease. Proc Natl Acad Sci USA 1985; 82: 4531–4534.CrossRefGoogle Scholar
77.Ayer-LeLievre, C, Olson, L, Ebendal, T, et al. Expression of the B nerve growth factor gene in hippocampal neurons. Science 1988; 240: 1339–1341.CrossRefGoogle Scholar
78.Dawbarn, D, Allen, SJ, Semenenko, FM. Coexistence of choline acetyltransferase and nerve growth factor receptors in the rat basal forebrain. Neurosci Lett 1988; 94: 138–144.CrossRefGoogle ScholarPubMed
79.Hyman, BT, Van Hoesen, GW, Damasio, AR. Alzheimer’s disease: glutamate depletion in the hippocampal perforant pathway zone. Ann Neurol 1987; 22: 37–40.CrossRefGoogle ScholarPubMed
80.Bowen, DM. Alzheimer’s disease. In: Davison, AN, Thompson, RHS, eds. The Molecular Basis of Neuropathology. London: Edward Arnold, 1981: 649–665.Google ScholarPubMed
81.Pearson, RCA, Powell, JPS. The neuroanatomy of Alzheimer’s disease. Rev Neurosci (in press).Google Scholar
82.Terry, RD. Ultrastructural alterations in senile dementia. In: Katzman, R, Terry, RD, eds. Alzheimer’s Disease: Senile Dementia and Related Disorders. (Aging, Vol 7). New York, Raven Press, 1978; 375–382.Google Scholar
83.Saraiva, AA, Borges, MM, Madeira, MD, et al. Mitochondrial abnormalities in cortical dendrites from patients with Alzheimer’s disease. J Submicroscopic Cytol 1985; 17: 459–464.Google ScholarPubMed
84.Sims, NR, Finegan, JM, Blass, JP, et al. Mitochondrial function in brain tissue in primary degenerative dementia. Brain Res 1987; 436: 30–38.CrossRefGoogle ScholarPubMed
85.Bowen, DM, Davison, AN. Cathepsin A in human brain and spleen. Biochem J 1973; 131: 417–419.CrossRefGoogle ScholarPubMed
86.Gottfries, CG, Kjallquist, A, Ponten, U, et al. Cerebrospinal fluid pH and monoamine and glucolytic metabolites in Alzheimer’s disease. Br J Psychiat 1974; 124: 280–287.CrossRefGoogle ScholarPubMed
87.Talamo, BR, Rudel, R, Kosik, KS, et al. Pathological changes in olfactory neurons in patients with Alzheimer’s disease. Nature 1989; 337: 736–739.CrossRefGoogle ScholarPubMed
88.Lennox, G, Lowe, J, Byrne, EJ, et al. Diffuse Lewy body disease. Lancet 1989; 1: 323–324.CrossRefGoogle ScholarPubMed
89.Mesulam, MM, Geula, C. Acetylcholinesterase – rich pyramidal neurons in the human neocortex and hippocampus: Absence at birth, development during the life span, and dissolution in Alzheimer’s disease. Ann Neurol 1988; 24: 765–773.CrossRefGoogle ScholarPubMed
90.Small, DH, Simpson, RJ. Acetylcholinesterase undergoes autolysis to generate trypsin-like activity. Neurosci Lett 1988; 89: 223–228.CrossRefGoogle ScholarPubMed
91.Jayson, D, Esiri, MM, Smith, AD. Histochemical evidence for a change in distribution and character of acetylcholinesterase in Alzheimer’s disease brain. Quart J Med (in press).Google Scholar
92.Gauthier, S, Masson, H, Gauthier, R, et al. Tetrahydroaminoacridine and lecithin in Alzheimer’s disease. In: Giacobini, E, Becker, R, eds. Current Research in Alzheimer Therapy. New York: Taylor and Francis 1988; 237–'245.Google Scholar
93.Balazs, R, Jorgensen, OS, Hack, N. N-Methyl-D-aspartate promotes the survival of cerebellar granule cells in culture. Neuroscience 1988; 27: 437–451.CrossRefGoogle ScholarPubMed
93.Brewer, GJ, Cotman, CW. NMDA promotes branching, MK801 stimulates elongation of dentate granule neurons. Soc Neurosci Abst 1988; 14: 115.Google Scholar
95.Waters, C. Cognitive enhancing agents: Current status in the treatment of Alzheimer’s disease. Can J Neurol Sci 1988; 15: 249–256.CrossRefGoogle ScholarPubMed
96.Neary, D, Snowden, JS, Bowen, DM, et al. Cerebral biopsy in the investigation of presenile dementia due to cerebral atrophy. J Neurol Neurosurg Psychiatry 1986; 49: 157–162.CrossRefGoogle ScholarPubMed