Thomas G Beach1. 1. Sun Health Research Institute, Sun City, Ariz. 85351, USA. thomas.beach@sunhealth.org
Abstract
BACKGROUND: Brain beta-amyloid (Abeta) deposition is an extremely common accompaniment of aging in humans and many other mammalian species. We hypothesized that normal physiological changes of aging cause Abeta deposition. OBJECTIVE: Three normal physiological aging changes were induced in young adult rabbits to determine their effects on brain Abeta 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 Abeta(42) concentrations and cerebrovascular Abeta deposition. Hypercholesterolemia increased cortical Abeta(42) 4.6-fold while ovariectomy increased cortical Abeta(42) 1.6-fold. CONCLUSION: At least three physiological changes of normal aging may underlie age-related brain Abeta accumulation and Alzheimer's disease. 2008 S. Karger AG, Basel
BACKGROUND: Brain beta-amyloid (Abeta) deposition is an extremely common accompaniment of aging in humans and many other mammalian species. We hypothesized that normal physiological changes of aging cause Abeta deposition. OBJECTIVE: Three normal physiological aging changes were induced in young adult rabbits to determine their effects on brain Abeta 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 Abeta(42) concentrations and cerebrovascular Abeta deposition. Hypercholesterolemia increased cortical Abeta(42) 4.6-fold while ovariectomy increased cortical Abeta(42) 1.6-fold. CONCLUSION: At least three physiological changes of normal aging may underlie age-related brain Abeta accumulation and Alzheimer's disease. 2008 S. Karger AG, Basel
Authors: Stephen Deci; Susan K Lemieux; Carrie A Smith-Bell; D Larry Sparks; Bernard G Schreurs Journal: J Alzheimers Dis Date: 2012 Impact factor: 4.472