Summary
Neurochemical investigations demonstrate that normal brain aging is characterized by a moderate decrease in glycolytic turnover capacity. There is an age-dependent increase in soluble hexokinase activity and a significant decrease in activity of the key glycolytic enzyme phosphofructokinase. This decrease in the glycolytic turnover capacity lowers acetyl coenzyme A, necessary for the biosynthesis of acetylcholine. Therefore normal aging of the brain is additionally characterized by a moderate decline of the cholinergic activity. The monaminergic neurotransmitters also decrease, which results in a neurotransmitter imbalance.
In normal aging the brain stays within the limits of the functional reserve capacity. This reserve capacity can be exhausted by ischemic, traumatic, or toxic brain lesions, shifting the normal aging brain into a psychoorganic defect syndrome or a senile dementia.
In Alzheimer’s disease and in senile dementia of Alzheimer’s type, in addition to a decrease of mitochondrial hexokinase and phosphofructokinase activity, there is a significant decrease in aldolase, triosephosphate isomerase, phosphoglucose isomerase, and phosphogylceromutase activity. The functional consequence of this decrease in glycolytic energy supply is a massive impairment of acetylcholine synthesis, which is accompanied by a massive decline in choline acetyltransferase. Senile dementia can be defined as a cholinergic insufficiency of the brain. A drug treatment which improves the glycolytic turnover may be an etiological theraphy concept enhancing cholinergic brain activity by increasing acetyl coenzyme A and choline acetyltransferase activity.
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References
Annau, Z.: The effect of carbonic anhydrase inhibition on electrical self-stimulation of the brain during hypoxia. Life Sci. 20, 1043–1050 (1977).
Blass, J.P., Gibson, G.E., Shimada, M., Kihara, T., Watanabe M., and Kurinioto, K.: Brain carbohydrate metabolism and dementias. In Roberts, P.J. (Ed.), Biochemistry of Dementia, pp. 121–134. London, England: John Wiley & Sons, 1980.
Bourke, R.S., Kimelberg, H.K., and Nelson, L.R.: The effects of temperature and inhibitors on HC03-stimulated swelling and ion uptake of monkey cerebral cortex. Brain Res. 105, 309–323 (1976).
Bowen, D.M., White, P., Spillane, J.A., Goodhardt, M.J., Curzon, G., Iwangoff, P., Meier-Ruge, W., and Davison, A.N.: Accelerated aging or selective neuronal loss as an important cause of dementia? Lancet I, 11–14 (1979).
Busse, E.W.: Duke longitudinal study. I: Senescence and senility. In Katzman, R., Terry, R.D., Bick, K.L. (Eds.), Alzheimer’s Disease: Senile Dementia and Related Disorders (Aging Vol. 7), pp. 59–68. New York: Raven, 1978.
Busse, E.W., and Wang, H.S.: The electroencephalographic changes in late life: A longitudinal study. J. Clin. Exp. Geront. 1, 145–158 (1979).
Butler, R.N.: Pharmacological interventions of the aging process. In Pharma¬cological Intervention in the Aging Process. Roberts, J., Adelman, R.C., and Cristofalo, V.J. (Eds.), New York, Plenum Press (1978).
Butler, R.N.: Alzheimer’s disease—senile dementia and related disorders: The role of NIA. In Alzheimer’s disease: Senile dementia and related disorders, pp. 5–9. Katzman, R., Terry, R.D., and Blick, K.L. (Eds.), Aging, Vol. 7, New York: Raven, 1978b.
Carlsson, A.: Age-dependent changes in central dopaminergic and other mono- aminergic systems. Adv. Exp. Med. Biol. 113, 1–13 (1978).
Carlsson, A., Adolfsson, R., Aquilonius, S.-M., Gottfries, C.-G., Oreland, L., Svennerholm, L., and Winblad, B.: Biogenic amines in human brain in normal aging, senile dementia and chronic alcoholism. In Goldstein, M., Calne, D.G., Lieberman, A., and Thorner, M.O. (Eds.): Ergot Compounds and Brain Function. Advances in Biochemical Psychopharmacology, Vol. 23, pp. 295–304. New York: Raven, 1980.
Davies, P., Katz, D.A., and Crystal, H.A.: Choline acetyltransferase, somatostatin and substance P in selected cases of Alzheimer’s disease. In Corkin, S. etal. (Eds.), Alzheimer’s Disease: A Report of Progress, pp. 9–14. New York: Raven, 1982.
Davis, K.L., and Yamamura, H.I.: Cholinergic underactivity in human memory disorders. Life Sci. 23, 1729–1734 (1978).
Frolkis, V.V., and Bezrukov, V.V.: Aging of the central nervous system. Interdiscipl. Topics Geront. (Karger, Basel) 16, 1–131 (1979).
Gibson, G.E., and Blass, J.P.: Impaired synthesis of acetylcholine in brain accompanying mild hypoxia and hypoglycemia. J. Neurochem. 27, 37–42 (1976).
Gibson, G.E., Schimada, M., and Blass, J.P.: Alterations in acetylcholine synthesis and cyclic nucleotides in mild cerebral hypoxia. J. Neurochem. 31, 757–760 (1978).
Gottstein, U.: Risk factors and cerebral blood flow and metabolism. Proc. Int. Cerebrovascular Diseases SIR 219–238.
Gottstein, U., and Held, K.: Effekt der Haemodilution nach intravenoser Infusion von niedermolekularen Dextranen auf die Hirnzirkulation des Menschen. Dtsch. Med. Wschr. 94, 522–526 (1969).
Heston, L.L.: Alzheimer’s dementia and Down’s Syndrome: Genetic evidence suggesting an association. Ann. N.Y. Acad. Sci. 396, 29–37 (1982).
Iwangoff, P., Armbruster, R., Enz, A., Meier-Ruge, W., and Sandoz, P.: Glycolytic enzymes from human autoptic brain cortex: Normally aged and demented cases. In Roberts, P.J. (Ed.), Biochemistry of Dementia, pp. 258–262. London: John Wiley & Sons, 1980.
Iwangoff, P., Enz, A., and Meier-Ruge, W.: Incorporation, after single and repeated application of radioactive labelled DH-ergot alkaloids in different organs of the cat, with special reference to the brain. Gerontology, Suppl. 1, 24, 126–138 (1978).
Iwangoff, P., Reichlmeier, K., Enz, A., and Meier-Ruge, W.: Neurochemical findings in physiological aging of the brain. Interdiscipl. Topics Gerontol. (Karger, Basel) 15, 13–33 (1979).
Katzman, R., and Karasu, T.: Differential diagnosis of dementia. In Field, W.S. (Ed.), Neurological and Sensory Disorders in the Elderly, pp. 103–104. New York: Stratton Intercont. Med. Book Corp., 1975.
Kimelberg, H.K., Biddlecome, S., Narumi, S., and Bourke, R.S.: ATPase and carbonic anhydrase activities of bulk-isolated neuron, glia and synaptosome fractions from rat brain. Brain Res. 141, 305–323 (1978).
McGeer, G., and McGeer, P.L.: Aging and neurotransmitter systems. In Goldstein, M., Calne, D.B., Lieberman, A., and Thorner, M.O. (Eds.), Ergot Compounds and Brain Function, Series Advances in Biochemical Psycho- pharmacology, Vol. 23., pp. 305–314. New York: Raven, 1980.
McGeer, E.G., and McGeer, P.L: Neurotransmitters in normal aging. In D. Piatt (Ed.), Geriatrics, Vol. 1, pp. 263–282. New York: Springer-Verlag, 1982.
Meier-Ruge, W.: Neurochemistry of the aging brain. In Piatt, D. (Ed.), Geriatrics, Vol. 1, pp. 241–256. New York: Springer-Verlag, 1982.
Meier-Ruge, W., Emmenegger, H., Enz, A., Gygax, P., Iwangoff, P., and Wiernsperger, N.: Pharmacological aspects of dihydrogenated ergot alkaloids in experimental brain research. Pharmacology 16, Suppl. 1, 45–62 (1978).
Meier-Ruge, W., Hunziker, 0., Iwangoff, P., Reichlmeier, K, and Sandoz, P.: Alterations of morphological and neurochemical parameters of the brain due to normal aging. In Nandy, K. (Ed.), Senile Dementia: A Biomedical Approach, Developmental Neuroscience Vol. 3., pp. 33–44. New York: Elsevier/North-Holland, 1978.
Meier-Ruge, W., Iwangoff, P., Reichlmeier, K., and Sandoz, P.: Neurochemical findings in the aging brain. In Goldstein, M. et al. (Eds.), Ergot Compounds and Brain Function: Neuroendocrine and Neuropsychiatric Aspects, Advances in Biomedical Psychopharmacology Vol. 23, pp. 323–338. New York: Raven, 1980.
Nordenson, I., Adolfsson, R., Beckman, G., Bucht, G., and Winblad, B.: Chromosomal abnormality in dementia of the Alzheimer type. Lancet 1, 481–482 (1980).
Obrist, W.D., and Busse, E.W.: The electroencephalogram in old age. In Wilson, W.P. (Ed.), Applications of Electroencephalography in Psychiatry, pp. 185–205. Durham: Duke University, 1965.
Olson, M.I., and Shaw, C.M.: Presenile dementia and Alzheimer’s disease in mongolism. Brain 92, 147–156 (1969).
Palacios, J.M.: Autoradiographic localization of muscarinic cholinergic receptors in the hippocampus of patients with senile dementia. Brain Res. 243, 173–175 (1982).
Perry, E.K.: The cholinergic system in old age and Alzheimer’s disease. Age and Ageing(England) 9, 1–8 (1980).
Perry, E.K., Tomlinson, B.E., Blessed, G., Bergmann, K., Gibson, P.H., and Perry, R.H.: Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Brit. Med. J. II, 1457–1459 (1978).
Reichlmeier, K., Enz, A., Iwangoff, P., and Meier-Ruge, W.: Age-related changes in human brain enzyme activities: A basis for pharmacological intervention. In Roberts, J., Adelman, R.C., and Cristofalo, V.J., Pharmacological Intervention in the Aging Process, Adv. Exper. Med. Biol., Vol. 97, pp. 251–252. New York: Plenum, 1978.
Reichlmeier, K., Iwangoff, P., Enz, A.: Enzymatic changes in the aging brain and some aspects of its pharmacological intervention with ergot compounds. In Eisdorfer, C., and Fann, W.E. (Eds.), Psychopharmacology of Aging, Chapter 2, pp. 13–46. New York: Spectrum, 1980.
Rossor, M.N., Emson, P.C., Iversen, L.L., Mountjoy, C.Q., Roth, M., Fahrenkrug, J., and Rehfeld, J.F.: Neuropeptides and neurotransmitters in cerebral cortex in Alzheimer’s disease. In Corkin, G. et al. (Eds.), Alzheimer’s Disease: A Report of Progress, Aging, Vol. 19, pp. 15–24. New York: Raven, 1982.
Roubicek, J.: The electroencephalogram in the middle-aged and the elderly. J. Am. Geriatr. Soc. 25, 145–152 (1977).
Samorajski, T.: Central neurotransmitter substances and aging: a review. J. Am. Geriatr. Soc. 25, 337–348 (1977).
Selby, Ph., and Schechter, M.: Aging 2000: A Challenge for Society. MTP Lancaster: MTP Press 1982.
Severinghaus, J.W., Hamilton, F.N., and Coter, S.: Carbonic acid production and the role of carbonic anhydrase in decarboxylation in brain. Biochem. J. 114, 703–705 (1969).
Siesjö, B.K., and Rehncrona, S.: Adverse factors affecting neuronal metabolism: Relevance to the dementias. In Roberts, P.J. (Ed.), Biochemistry of Dementia, pp. 91–120. London: John Wiley & Sons, 1980.
Sokoloff, L.: Cerebral circulation and metabolism in the aged. In Gershon, A., and Raskin, A. (Eds.), Genesis and Treatment of Psychologic Disorders in the Elderly, Aging, Vol. 2, pp. 45–54. New York: Raven, 1975.
Sylvia, A.L., and Rosenthal, M.: The effect of age and lung pathology on cytochrome a,a3 redox levels in rat cerebral cortex. Brain Res. 146, 109–122 (1978).
Sylvia, A.L., and Rosenthal, M.: Effects of age on brain oxidative metabolism in vivo. Brain Res. 165, 235–248 (1979).
Whalley, L.J.: The dementia of Down’s Syndrome and its relevance to aetiological studies of Alzheimer’s disease. Ann. N.Y. Acad. Sci., 386, 39–53 (1982).
Whalley, L.J., Carothers, A.D., Collyer, S., DeMey, R., and Frackiewicz, A.: A study of familial factors in Alzheimer’s disease. Brit. J. Psychiatr. 140, 249–256 (1982).
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Meier-Ruge, W. (1985). Neurochemistry of the Aging Brain and Senile Dementia. In: Gaitz, C.M., Samorajski, T. (eds) Aging 2000: Our Health Care Destiny. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-5058-6_8
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DOI: https://doi.org/10.1007/978-1-4612-5058-6_8
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