title: Inducing autophagy by rapamycin before, but not after, the formation of plaques and tangles ameliorates cognitive deficits.
abstract: Previous studies have shown that inducing autophagy ameliorates early cognitive deficits associated with the build-up of soluble amyloid-β (Aβ). However, the effects of inducing autophagy on plaques and tangles are yet to be determined. While soluble Aβ and tau represent toxic species in Alzheimer's disease (AD) pathogenesis, there is well documented evidence that plaques and tangles also are detrimental to normal brain function. Thus, it is critical to assess the effects of inducing autophagy in an animal model with established plaques and tangles. Here we show that rapamycin, when given prophylactically to 2-month-old 3xTg-AD mice throughout their life, induces autophagy and significantly reduces plaques, tangles and cognitive deficits. In contrast, inducing autophagy in 15-month-old 3xTg-AD mice, which have established plaques and tangles, has no effects on AD-like pathology and cognitive deficits. In conclusion, we show that autophagy induction via rapamycin may represent a valid therapeutic strategy in AD when administered early in the disease progression.
authors: Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors: Smita
authors: S
authors: Majumder
authors: Arlan
authors: A
authors: Richardson
authors: Randy
authors: R
authors: Strong
authors: Salvatore
authors: S
authors: Oddo
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy*; D008569:Memory Disorders / Q000188:drug therapy; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000187:drug effects* / Q000473:pathology*; D058225:Plaque, Amyloid / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D012307:Risk Factors; D020123:Sirolimus / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D020123:Sirolimus