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F5‐02‐04: Pathological outcome of APP and tau interaction in the entorhinal cortex
Author(s) -
Elizabeth Karen
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.2334
Subject(s) - entorhinal cortex , hippocampal formation , genetically modified mouse , transgene , hippocampus , phenotype , neuroscience , mutant , pathological , psychology , biology , pathology , medicine , gene , genetics
Background: A possible link between a deficient neurogenesis at the dentate gyrus and the loss of memory and cognitive decline found in Alzheimer’s disease patients has been suggested. In the deficient neurogenesis,GSK3 (also known as tau-1 kinase) could play a role. In both, familial and sporadic disease has been suggestedan increase inGSK3activity, beingoneof themain substrates for this kinase, tau protein.Methods:We have studied the effect of GSK3b overexpression in dentate gyrus neurogenesis in a conditional transgenic GSK3b mouse and in double transgenic mouse overexpressing GSK3 and human tau protein.Results:We found that GSK3 overexpression in dentate gyrus (DG) reduces the number of neurogenic niches present at the subgranular zone and impairs maturation in the newborn cells. In this process, tau phosphorylated by GSK3 could play a toxic role. As a consequence, a decrease in DG volume was observed together with a memory impairment tested by behavioral tests. Conclusions:We propose that a long overexpression of GSK3b at the dentate gyrus could result in the depletion of neurogenic niches. In the absence of those niches, no newborn neurons are present. It may result in a memory and cognitive decline.