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The Interplay of Neurotransmitters in Alzheimer's Disease

Published online by Cambridge University Press:  07 November 2014

Paul T. Francis
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Abstract

Evidence exists for both cholinergic and glutamatergic involvement in the etiology of Alzheimer's disease. Acetylcholine (ACh), a neurotransmitter essential for processing memory and learning, is decreased in both concentration and function in patients with Alzheimer's disease. This deficit and other presynaptic cholinergic deficits, including loss of cholinergic neurons and decreased acetylcholinesterase activity, underscore the cholinergic hypothesis of Alzheimer's disease. The glutamatergic hypothesis links cognitive decline in patients with Alzheimer's to neuronal damage resulting from overactivation of N-methyl-D-aspartate (NMDA) receptors by glutamate. The sustained low-level activation of NMDA receptors, which are pivotal in learning and memory, may result from deficiencies in glutamate reuptake by astroglial cells in the synaptic cleft. This article reviews the roles of ACh and glutamate in Alzheimer's disease, with particular attention given to the overlap between cholinergic and glutamatergic pathways. In addition, the potential synergy between cholinesterase inhibitors and the NMDA receptor antagonist memantine in correcting neurologic abnormalities associated with Alzheimer's disease is addressed.

Type
Academic Supplement
Information
CNS Spectrums , Volume 10 , Issue S18: Alzheimer's Disease Pathways to Practice: Assessing Diagnosis and Outcome Measures , November 2005 , pp. 6 - 9
Copyright
Copyright © Cambridge University Press 2005

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References

REFERENCES

1.Bussiere, T, Giannakopoulos, P, Bouras, C, et al.Progressive degeneration of nonphosphorylated neurofilament protein-enriched pyramidal neurons predicts cognitive impairment in Alzheimer's disease: stereologic analysis of prefrontal cortex area 9. J Comp Neurol. 2003;463:281–302.Google Scholar
2.Mirra, SS, Hart, MN, Terry, RD. Making the diagnosis of Alzheimer's disease. A primer for practicing pathologists. Arch Pathol Lab Med. 1993;117:132–144.Google ScholarPubMed
3.Francis, PT, Palmer, AM, Snape, M, Wilcock, GK. The cholinergic hypothesis of Alzheimer's disease: a review of progress. J Neurol Neurosurg Psychiatry. 1999;66:137–147.CrossRefGoogle ScholarPubMed
4.Drachman, DA, Leavitt, J. Human memory and the cholinergic system. A relationship to aging? Arch Neurol. 1974;30:113–121.CrossRefGoogle ScholarPubMed
5.Sims, NR, Bowen, DM, Allen, SJ, et al.Presynaptic cholinergic dysfunction in patients with dementia. J Neurochem. 1983;40:503–509.CrossRefGoogle ScholarPubMed
6.Francis, PT, Palmer, AM, Sims, NR, et al.Neurochemical studies of earlyonset Alzheimer's disease. Possible influence on treatment. N Engl J Med. 1985;313:7–11.CrossRefGoogle ScholarPubMed
7.Francis, PT, Sims, NR, Procter, AW, Bowen, DM. Cortical pyramidal neurone loss may cause glutamatergic hypoactivity and cognitive impairment in Alzheimer's disease: investigative and therapeutic perspectives. J Neurochem. 1993;60:1589–1604.CrossRefGoogle ScholarPubMed
8.Gsell, W, Strein, I, Riederer, P. The neurochemistry of Alzheimer type, vascular type and mixed type dementias compared. J Neural Transm Suppl. 1996;47:73–101.CrossRefGoogle ScholarPubMed
9.Squire, LR, Zola-Morgan, S. The medial temporal lobe memory system. Science. 1991;253:1380–1386.Google Scholar
10.Procter, AW, Francis, PT, Holmes, C, et al.beta-amyloid precursor protein isoforms show correlations with neurones but not with glia of demented subjects. Acta Neuropathol (Berl). 1994;88:545–552.CrossRefGoogle Scholar
11.Lauderback, CM, Hackett, JM, Huang, FF, et al.The glial glutamate transporter, GLT-1, is oxidatively modified by 4-hydroxy-2-nonenal in the Alzheimer's disease brain: the role of Abetal-42. J Neurochem. 2001;78:413–416.CrossRefGoogle Scholar
12.Westphalen, RI, Scott, HL, Dodd, PR. Synaptic vesicle transport and synaptic membrane transporter sites in excitatory amino acid nerve terminals in Alzheimer disease. J Neural Transm. 2003;110:1013–1027.Google Scholar
13.Danysz, W, Parsons, CG, Möbius, HJ, Stöffler, A, Quack, G. Neuroprotective and symptomalogical action of memantine relevant for Alzheimer's disease: a unified glutamatergic hypothesis on the mechanism of action. Neurotox Res. 2000;2:85–97.CrossRefGoogle Scholar
14.Rowan, MJ, Klyubin, I, Cullen, WK, Anwyl, R. Synaptic plasticity in animal models of early Alzheimer's disease. Philos Trans R Soc Lond B Biol Sci. 2003;358:821–828.Google Scholar
15.Walsh, DM, Selkoe, DJ. Deciphering the molecular basis of memory failure in Alzheimer's disease. Neuron. 2004;44:181–193.CrossRefGoogle ScholarPubMed
16.Dijk, SN, Francis, PT, Stratmann, GC, Bowen, DM. Cholinomimetics increase glutamate outflow via an action on the corticostriatal pathway: implications for Alzheimer's disease. J Neurochem. 1995;65:2165–2169.CrossRefGoogle ScholarPubMed