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Article type: Research Article
Authors: Schreurs, Bernard G.a; * | Sparks, D. Larryb; †
Affiliations: [a] West Virginia University and Blanchette Rockefeller Neurosciences Institute, Morgantown, WV, USA | [b] Banner Health Research Institute, Sun City, AZ, USA
Correspondence: [*] Correspondence to: Bernard G. Schreurs, Ph.D., Department of Physiology and Pharmacology, 1024 BRNI Building, Morgantown, WV 26505, USA. Tel.: +1 304 293 0497; Fax: +1 304 293 7536; E-mail: bschreurs@hsc.wvu.edu
Note: [†] D. Larry Sparks passed away on May 14, 2013.
Abstract: Background:Cholesterol-fed rabbits have been documented to show increased amyloid-β (Aβ) deposits in the brain that can be exacerbated by the quality of drinking water especially if rabbits drink tap water or distilled water containing copper. One mechanism of cholesterol and Aβ clearance may be through the ATP-binding cassette transporter A1 (ABCA1). Objective and Methods:Using an ABCA1 antibody, we determined the number of ABCA1-immunopositive neurons in three areas of rabbit brain as a function of feeding 2% cholesterol and providing tap water, distilled water, or distilled water to which aluminum, copper, or zinc was added. Results:The number of neurons with ABCA1 immunoreactivity was increased significantly as a result of dietary cholesterol in the rabbit hippocampus and inferior and superior temporal cortex. The number of neurons with ABCA1 immunoreactivity was further increased in all three areas as a result of cholesterol-fed rabbits drinking tap water or distilled water with copper. Finally, cholesterol-fed rabbits that drank distilled water with aluminum also showed an increased number of ABCA1-immunopositive neurons in inferior and superior temporal cortex. Conclusions:These data suggest that ABCA1 levels increase in parallel with previously documented increases in Aβ levels as a result of high dietary cholesterol and copper in the drinking water. Addition of aluminum to distilled water may have a similar effect in the temporal cortex. ABCA1 has been proposed as a means of clearing Aβ from the brain and manipulations that increase Aβ also result in an increase of clearance machinery.
Keywords: Aluminum, ATP-binding cassette transporter A1, cholesterol-fed rabbit, copper, zinc
DOI: 10.3233/JAD-150601
Journal: Journal of Alzheimer's Disease, vol. 49, no. 1, pp. 201-209, 2016
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