Physiologic origins of age-related beta-amyloid deposition

Background: Brain beta-amyloid (A beta) deposition is an extremely common accompaniment of aging in humans and many other mammalian species. We hypothesized that normal physiological changes of aging cause A beta deposition. Objective: Three normal physiological aging changes were induced in young adult rabbits to determine their effects on brain A beta 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 A beta(42) concentrations and cerebovascular A beta deposition. Hypercholesterolemia increased cortical A beta(42) 4.6-fold while ovariectomy increased cortical A beta(42) 1.6-fold. Conclusion: At least three physiological changes of normal aging may underlie age-related brain A beta accumulation and Alzheimer's disease. Copyright (c) 2008 S. Karger AG, Basel.