Insulin degrading enzyme over-expression is associated with amyloid ß plaque development.

DORFMAN, V; CASTAÑO, EM; MORELLI, L

Pinamar, Argentina

Congreso; PABMB 10th Congress, SAIB 41th Annual Meetin and SAN 20th Annual Meeting.; 2005

Insulin degrading enzyme (IDE) is implicated in amyloid b (Ab) degradation. Previously we reported the presence of IDE around the amyloid plaques from old transgenic mice Tg2576 (Tg) overexpressing a mutated form of human Ab precursor protein used as animal model of Alzheimer`s disease (AD). The aim was to evaluate if IDE distribution, its expression and Ab accumulation are time-course related events. Cryostat coronal brain sections of 11, 15, 17 and 23 months of age (m) Tg and non-transgenic (NTg) mice were subjected to semi-quantitative immunohistochemistry (ImagePro software) (n=4/group) to evaluate Ab (S40 antibody), IDE (1C1 antibody), astrocytes (anti-GFAP) and microglia (tomato lectin, lycopersicon esculentum) reactivity. Tg mice beyond 11 m presented Ab deposits in hippocampus, cerebral cortex, amygdala and corpus callosum, with a sharp age-dependent increase in the number of the deposits between 17 and 23 m. Ab deposition showed reactive gliosis, with increasing numbers of astrocytes and microglial cells surrounding the plaques. IDE was observed at similar levels in the cytoplasm of neurons in Tg and NTg, at all evaluated ages. In addition, a strong IDE immunoreactivity, that co-localized with activated glial cells, was detected surrounding 14 % of Ab deposits in 15 m Tg and 100 % of plaques in 17 and 23 m Tg. IDE plaques mean diameter ranged form 30 to 100 µm, with no size variations among different ages. These results suggest that Ab plaque-deposition is synchronous with glial IDE overexpression and may limit plaque growth in this model of AD (IIRG 03-5312, PICT 05-10599).