Mechanism for anti-AD effect of approved medicines

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Transforming growth factor (TGF)-B1 stimulates this phagocytosis. We recently reported that the APP23 mouse model for AD showed fewer AD-related phenotypes when these animals were crossed with transgenic mice expressing heat shock protein (HSP) 70. We here examined the effect of geranylgeranylacetone, an inducer of HSP70 expression, on the AD-related phenotypes. Repeated oral administration of geranylgeranylacetone to APP23 mice for 9 months not only improved cognitive function but also decreased levels of AB, AB plaque deposition and synaptic loss. The treatment also up-regulated the expression of an AB-degrading enzyme and TGF-B1 but did not affect the maturation of APP and secretase activities. These outcomes were similar to those observed in APP23 mice genetically modified to overexpress HSP70. A single oral administration of geranylgeranylacetone significantly increased the level of HSP70 when AB was concomitantly injected directly into the hippocampus.