Genetic Reduction of Mammalian Target of Rapamycin Ameliorates Alzheimer's Disease-like Cognitive and Pathological Deficits by Restoring Hippocampal Gene Expression Signature

Overview

Journal J Neurosci

Specialty Neurology

Date 2014 Jun 6

PMID 24899720

Citations 110

Authors

Antonella Caccamo

Vito De Pinto

Angela Messina

Caterina Branca

Salvatore Oddo

Affiliations

Soon will be listed here.

Abstract

Elevated mammalian target of rapamycin (mTOR) signaling has been found in Alzheimer's disease (AD) patients and is linked to diabetes and aging, two known risk factors for AD. However, whether hyperactive mTOR plays a role in the cognitive deficits associated with AD remains elusive. Here, we genetically reduced mTOR signaling in the brains of Tg2576 mice, a widely used animal model of AD. We found that suppression of mTOR signaling reduced amyloid-β deposits and rescued memory deficits. Mechanistically, the reduction in mTOR signaling led to an increase in autophagy induction and restored the hippocampal gene expression signature of the Tg2576 mice to wild-type levels. Our results implicate hyperactive mTOR signaling as a previous unidentified signaling pathway underlying gene-expression dysregulation and cognitive deficits in AD. Furthermore, hyperactive mTOR signaling may represent a molecular pathway by which aging contributes to the development of AD.

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