The Effect of Dietary Micro and Macronutrients on Amyloid pathology in a Transgenic Mouse Model of Alzheimer's Disease





D. Morgan, M.N. Gordon, G. DiCarlo, K Connor, R.A. Good, C.L. Walker and R.W. Engelman

Alzheimer Research Laboratory
University of South Florida
12901 Downs Blvd MDC Box 9
Tampa FL 33612-4799




Calorie restriction without malnutrition is a robust method
of modifying age-related changes in physiology and behavior.
Mice made transgenic with mutated forms of the amyloid
precursor protein and presenilin-1 protein develop
pathological changes similar to those found in Alzheimer's
dementia. Mice were given a semi-purified diet between 2
and 6 months of age, with one group restricted ~40% in
caloric intake, leading to 35% reductions in body mass at
the end of the study. Brain sections were stained for Aß
peptide, Congo red and GFAP. Calorie restriction resulted in
a significant 65% reduction in Aß immunostaining in the
frontal cortex, and a nonsignificant 40% reduction in the
CA1 region of hippocampus. Congo red staining revealed a
simlar 65% reduction in amyloid content of the frontal
cortex and a significant 50% reduction in the CA1 region
of hippocampus. GFAP staining was also reduced in the
restricted mice in cortical regions. These data indicate
that calorie restriction modifies not only the normal
physiological changes associated with natural aging, but can
also modify the expression of a pathological phenotype
caused by the artifical overexpression of a transgene.
Longer term studies will be necessary to determine if
calorie restriction might have merit in treating AD patients.
Continuing studies evaluating the influences of dietary
supplementation with blueberry extract, or comparison of
pathology in mice given diets supplemented or deficient in
metals may also be presented at the meeting.
Supported by the NIA AG 15490 and AG18478.




Key words: Calorie restriction, amyloid, transgenic, amyloid precursor protein, A-beta







Problems or questions regarding this site should be directed to webmaster@americanaging.org