Abstract
Background: Brain β-amyloid (Aβ) deposition is an extremely common accompaniment of aging in humans and many other mammalian species. We hypothesized that normal physiological changes of aging cause Aβ deposition. Objective: Three normal physiological aging changes were induced in young adult rabbits to determine their effects on brain Aβ concentrations and deposition. The three changes were cortical cholinergic deafferentation, hypercholesterolemia and estrogen deprivation. Methods: Cortical cholinergic deafferentation was achieved through intracerebroventricular immunotoxin injection. Hypercholesterolemia was induced with a 2% cholesterol diet. Estrogen deprivation was modeled with ovariectomy. Results: Cortical cholinergic deafferentation resulted in an 8-fold increase in cortical Aβ<sub>42</sub> concentrations and cerebovascular Aβ deposition. Hypercholesterolemia increased cortical Aβ<sub>42</sub> 4.6-fold while ovariectomy increased cortical Aβ<sub>42</sub> 1.6-fold. Conclusion: At least three physiological changes of normal aging may underlie age-related brain Aβ accumulation and Alzheimer’s disease.
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