Hostname: page-component-7c8c6479df-27gpq Total loading time: 0 Render date: 2024-03-27T22:41:07.741Z Has data issue: false hasContentIssue false

Neuronal Lipofuscin Accumulation in Ageing and Alzheimer Dementia: A Pathogenic Mechanism?

Published online by Cambridge University Press:  29 January 2018

J. H. Dowson*
Affiliation:
University of Cambridge Clinical School, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ

Summary

The amount of intraneuronal lipofuscin in the parietal cortex and in the inferior olivary nucleus was measured in post-mortem tissue affected by Alzheimer dementia and in specimens from non-demented individuals. The results indicate that there is a linear relationship between the accumulation of cell body lipofuscin and advancing age, both in neuronal populations of the non-demented group, and in the olivary neurones of the demented group. However, in the demented group, the lipofuscin fluorescence intensity of the parietal neurones was not significantly correlated with age. The estimated amount of lipofuscin in the olivary neurones in the demented group was significantly higher than in the non-demented group, when age has been taken into account (P <0.01). The possible pathogenic role of lipofuscin accumulation in ageing and Alzheimer dementia is discussed.

Type
Research Article
Copyright
Copyright © Royal College of Psychiatrists, 1982 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Blaauboer, A. J., Novak, L. & Hooghwinkel, G. J. M. (1979) Organic solvent soluble lipofuscin pigment in brain tissues of mice fed large amounts of polyunsaturated fats in presence and absence of various antioxidants. International Journal for Vitamin and Nutrition Research, 49, 428–33.Google Scholar
Brizzee, K. R. (1975) Ageing changes in relation to diseases of the nervous system. In Neurobiology of Ageing (eds. Ordy, J. M. and Brizzee, K. R.). New York and London: Plenum Press.Google Scholar
Brizzee, K. R. & Cancilla, P. A. (1972) Differential accumulation of lipofuscin pigment in cerebral cortex of rat. Gerontologia, 18, 113.Google Scholar
Brizzee, K. R., Kaack, B. & Klara, P. (1975) Lipofuscin: Intra and extraneuronal accumulation and regional distribution. In Neurobiology of Ageing (eds. Ordy, J. M. and Brizzee, K. R.). New York and London: Plenum Press.Google Scholar
Brizzee, K. R. & Knox, C. (1980) The ageing process in the neurone Advances in Experimental Medicine and Biology, 129, 7198.Google Scholar
Brizzee, K. R., Ordy, J. M. & Kaack, B. (1974) Early appearance and regional differences in intraneuronal and extraneuronal lipofuscin accumulation with age in the brain of a non-human primate. Journal of Gerontology, 29, 366–81.CrossRefGoogle Scholar
Dowson, J. H. & Harris, S. J. (1981) Quantitative studies of the autofluorescence derived from neuronal lipofuscin. Journal of Microscopy, 123, 249–58.CrossRefGoogle ScholarPubMed
Earnest, M. P., Heaton, R. K., Wilkinson, W. E. & Manke, W. F. (1979) Cortical atrophy, ventricular enlargement and intellectual impairment in the aged. Neurology, 29, 1138–43.Google Scholar
Gedye, J. C., Exton-Smith, A. N. & Wedgewood, J. (1972) A method for measuring mental performance in the elderly and its use in a pilot clinical trial of meclofenoxate. Age and Ageing, 1, 7480.Google Scholar
Glees, P. & Hassan, M. (1976) Lipofuscin in neuronal ageing and diseases. Normal and Pathological Anatomy (Stuttgart), 32, 168.Google Scholar
Katz, M. L., Stone, W. L. & Dratz, E. A. (1978) Fluorescent pigment accumulation in retinal pigment epithelium of antioxidant-deficient rats. Investigative Ophthalmology and Visual Science, 17, 1049–57.Google ScholarPubMed
Kent, S. (1976) Solving the riddle of lipofuscin origin may uncover clues to the ageing process. Geriatrics, May, 128–37.Google Scholar
Kugler, von J., Doenicke, A. & Harker, E. (1973) Course of thiopental anaesthesia under the influence of centrophenoxine. Arzneimittel-Forschung, 23, 82–5.Google Scholar
Ledvina, M. & Hodanova, M. (1980) The effect of simultaneous administration of tocopherol and sunflower oil on the life-span of female mice. Experimental Gerontology, 15, 6771.Google Scholar
Malamud, N. (1972) Neuropathology of organic brain syndromes associated with ageing. Advances in Behavioral Biology, 3, 6388.Google Scholar
Mann, D. M. A. & Sinclair, K. G. A. (1978) The quantitative assessment of lipofuscin pigment, cytoplasmic RNA and nucleolar volume in senile dementia. Neuropathology and Applied Neurobiology, 4, 129–35.Google Scholar
Mann, D. M. A. & Yates, P. O. (1974) Lipoprotein pigments—their relationship to ageing in the human nervous system. Brain, 97, 481–8.Google Scholar
Mann, D. M. A., Yates, P. O. & Barton, C. M. (1977) Cytophotometric mapping of neuronal changes in senile dementia. Journal of Neurology, Neurosurgery and Psychiatry, 40, 299302.CrossRefGoogle ScholarPubMed
Mann, D. M. A., Yates, P. O. & Stamp, J. E. (1978) The relationship between lipofuscin pigment and ageing in the human nervous system. Journal of Neurological Science, 37, 8393.Google Scholar
Marcer, D. & Hopkins, S. M. (1977) The differential effects of meclofenoxate on memory loss in the elderly. Age and Ageing, 6, 123–31.CrossRefGoogle ScholarPubMed
Monagle, R. D. & Brody, H. (1974) The effects of age upon the main nucleus of the inferior olive in the human. Journal of Comparative Neurology, 155, 61–6.Google Scholar
Nandy, K. (1978) Centrophenoxine: Effects on ageing mammalian brain. Journal of American Geriatric Society, 26, 7481.Google Scholar
Ploem, J. S. (1977) Quantitative fluorescence microscopy. In Analytical and Quantitative Methods in Microscopy (eds. Meek, G. A. and Elder, H. Y.). Cambridge University Press.Google Scholar
Riga, S. & Riga, D. (1974) Effects of centrophenoxine on the lipofuscin pigments in the nervous system of old rats. Brain Research, 72, 265–75.Google Scholar
Sandoz, P. & Meier-Ruge, W. (1977) Age-related loss of nerve cells from the human inferior olive, and unchanged volume of its gray matter. IRCS (International Research Communications System) Journal of Medical Science, 5, 376.Google Scholar
Scholtz, L. L. & Brown, A. (1978) Lipofuscin and transsynaptic degeneration. Virchows Archiv für pathologische Anatomie und Physiologie, 281, 3540.Google Scholar
Sharma, S. P. & Manocha, S. L. (1977) Lipofuscin formation in the developing nervous system of squirrel monkeys consequent to maternal dietry protein deficiency during gestation. Mechanisms of Ageing and Development, 6, 114.CrossRefGoogle Scholar
Siakotos, A. N. & Armstrong, D. (1975) Age pigment, a biochemical indicator of intracellular ageing. In Neurobiology of Ageing (eds. Ordy, J. M. and Brizzee, K. R.). New York and London: Plenum Press.Google Scholar
Siegel, S. (1956) Non-parametric Statistics. London: McGraw-Hill.Google Scholar
Snedecor, G. W. & Cochran, W. G. (1976) Analysis of covariance. In Statistical Methods. Iowa State University Press.Google Scholar
Spoerri, P. E. & Glees, P. (1975) The mode of lipofuscin removal from hypothalamic neurones. Experimental Gerontology, 10, 225–8.Google Scholar
Strehler, B. L., Mark, D. D., Mildvan, A. S. & Gee, M. V. (1959) Rate and magnitude of age pigment accumulation in the human myocardium. Journal of Gerontology, 14, 430–9.Google Scholar
Torack, R. M. (1978) The Pathologic Physiology of Dementia. Berlin: Springer.CrossRefGoogle ScholarPubMed
West, C. D. (1979) A quantitative study of lipofuscin accumulation with age in normals and individuals with Down's syndrome, phenylketonuria, progeria and transneuronal atrophy. Journal of Comparative Neurology, 186, 109–16.Google ScholarPubMed
Wing, G. L., Blanchard, G. C. & Weiler, J. J. (1978) The topography and age relationship of lipofuscin concentration in the retinal pigment epithelium. Investigative Ophthalmology and Visual Science, 17, 101–7.Google Scholar
Yamada, M. (1978) On the distribution of senile changes in the spinal cord. Folia psychiatrica et neurologica Japonica, 32, 249–51.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.