Cholesterol, copper, and accumulation of thioflavine S-reactive Alzheimer’s-like amyloid β in rabbit brain
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Accumulation of β-amyloid (Aβ) in the Alzheimer’s disease (AD) brain is considered to be causally related to the behavioral symptoms of the disorder. Transgenic mouse models of AD exhibit accumulation of Aβ in the brain and simultaneous memory deficits, and Aβ accumulation is enhanced if dietary cholesterol is administered. Likewise, dietary cholesterol induces neuronal accumulation of Aβ in New Zealand white rabbits. The cholesterol-induced accumulation of Aβ in rabbit brain is increased when distilled drinking water is supplemented with 0.12 ppm copper ion (as copper sulfate) compared to the cholesterol-induced accumulation of Aβ in rabbit brain of animals given unaltered distilled water. The numbers of affected neurons and the intensity of neuronal Aβ immunoreactivity is consistently increased among animals administered the copper ion in their drinking water. A copper-induced decrease in the clearance of overproduced Aβ from the brain is proposed as the mechanism causing Aβ accumulation and resulting in the observed memory deficits. Current studies reveal that intensely immunoreactive neurons, extracellular deposits of Aβ, and brain vessels in cholesterol-fed rabbits given copper-supplemented water were stained by thioflavine S. Thioflavine S-reactive features were not observed in cholesterol-fed rabbits given unaltered distilled drinking water. The data suggest that there is an accumulation of fibrillar Aβ induced in the brains of rabbits fed a cholesterol diet and administered trace levels of copper ion in their drinking water.
Index EntriesAlzheimer’s pathology cholesterol copper water quality amyloid
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- Atwood C. S., Scarpa R. C., Huang X., Moiré R. D., Jones W. D., Fairly D. P., et al. (2000) Characterization of copper interactions with Alzheimer amyloid beta peptides: Identification of an attomolar-affinity copper binding site on amyloid beta1-42. J. Neurochem. 75, 1219–1233.PubMedCrossRefGoogle Scholar
- Austen B. M., Frears E. R., and Davies H. (2000) Cholesterol upregulates production of Abeta 1–40 and 1–42 in transfected cells. Neurobiol. Aging 21, S254.Google Scholar
- Bales K. R., Fishman C., DeLong C., Du Y., Jordan W., and Paul S. M. (2000) Diet-induced hyperlipidemia accelerates amyloid deposition in the APPv717f transgenic mouse model of Alzheimer’s disease. Neurobiol. Aging 21, S139.Google Scholar
- Bergmann C., Runz H., Jakala P., and Hartmann T. (2000) Diversification of gamma-secretase versus beta-secretase inhibition by cholesterol depletion. Neurobiol. Aging 21, S278.Google Scholar
- Beyreuther K. (2000) Physiological function of APP processing. Neurobiol. Aging 21, S69.Google Scholar
- DeMattos R. B., Bales K. R., Cummins D. J., Dodart J. C., Paul S. M., and Holtzman D. M. (2001) Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer’s disease. Proc. Natl. Acad. Sci. U. S. A. 98, 8850–8855.PubMedCrossRefGoogle Scholar
- Durham R. A., Parker C. A., Emmerling M. R., Bisgaier C. L., and Walker L. C. (1998) Effect of age and diet on the expression of beta-amyloid 1–40 and 1–42 in the brains of apolipoprotein-E-deficient mice. Neurobiol. Aging 19, S281.Google Scholar
- Li L., Zeigler S., Lindsey R. J., and Fukuchi K. (1999) Effects of an atherogenic diet on amyloidosis in transgenic mice overexpressing the C-terminal portion of b-amyloid precurson protein. Soc. Neurosci. 25, 1859.Google Scholar
- Sparks D. L. (1997) Dietary cholesterol induces Alzheimer-like β-amyloid immunoreactivity in rabbit brain. Nutr. Metab. Cardiovasc. Dis. 7, 255–266.Google Scholar
- Sparks D. L. (1999) Neuropathologic links between Alzheimer’s disease and vascular disease, in Alzheimer’s Disease and Related Disorders, Iqbal K., Swaab D. F., Winblad B., Wisniewski H. M., eds., John Wiley, Chichester, West Sussex, England, pp. 153–163.Google Scholar
- Sparks D. L., Lochhead J., Horstman D., Wagoner T., and Martin T. (2002) Water quality has a pronounced effect on cholesterol-induced accumulation of Alzheimer amyloid b (Ab) in rabbit brain. J. Alzheimer Dis. 4, 523–529.Google Scholar