Alzheimer's disease and insulin resistance: translating basic science into clinical applications
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TLDR
A hypothesis is put forward on how a cross-talk between peripheral tissues and the brain might influence the development of AD, and a rational basis for the use of antidiabetic agents as novel and potentially effective therapeutics in AD is discussed.Abstract:
Alzheimer’s disease (AD) and diabetes are currently considered among the top threats to human health worldwide. Intriguingly, a connection between these diseases has been established during the past decade, since insulin resistance, a hallmark of type 2 diabetes, also develops in Alzheimer brains. In this article, the molecular and cellular mechanisms underlying defective brain insulin signaling in AD are discussed, with emphasis on evidence that Alzheimer’s and diabetes share common inflammatory signaling pathways. I put forward here a hypothesis on how a cross-talk between peripheral tissues and the brain might influence the development of AD, and highlight important unanswered questions in the field. Furthermore, I discuss a rational basis for the use of antidiabetic agents as novel and potentially effective therapeutics in AD.read more
Citations
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Journal ArticleDOI
Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums
Steven E. Arnold,Zoe Arvanitakis,Shannon L. Macauley-Rambach,Aaron M. Koenig,Hoau Yan Wang,Rexford S. Ahima,Suzanne Craft,Sam Gandy,Christoph Buettner,Luke E. Stoeckel,David M. Holtzman,David M. Nathan +11 more
TL;DR: Key observations and experimental data on insulin signalling in the brain are reviewed and the concept of 'brain insulin resistance' is defined and the growing, although still inconsistent, literature concerning cognitive impairment and neuropathological abnormalities in T2DM, obesity and insulin resistance is reviewed.
Journal ArticleDOI
The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade
TL;DR: If the momentum of AβO research continues, particularly efforts to elucidate key aspects of structure, a clear path to a successful disease modifying therapy can be envisioned, and lessons learned from recent, late-stage clinical failures are applied appropriately throughout therapeutic development will further enable the likelihood of a successful therapy in the near-term.
Journal ArticleDOI
Inflammation, Defective Insulin Signaling, and Mitochondrial Dysfunction as Common Molecular Denominators Connecting Type 2 Diabetes to Alzheimer Disease
TL;DR: Evidence indicating that inflammation, insulin resistance, and mitochondrial dysfunction are common features in AD and T2D are reviewed and the hypothesis that dementia and its underlying neuronal dysfunction are exacerbated or driven by peripheral inflammation is proposed.
Journal ArticleDOI
Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer's models
Mychael V. Lourenco,Mychael V. Lourenco,Rudimar Luiz Frozza,Rudimar Luiz Frozza,Guilherme B. L. de Freitas,Guilherme B. L. de Freitas,Hong Zhang,Grasielle C. Kincheski,Felipe C. Ribeiro,Rafaella Araujo Gonçalves,Julia R. Clarke,Danielle Beckman,Agnieszka Staniszewski,Hanna Berman,Lorena A. Guerra,Leticia Forny-Germano,Shelby E. Meier,Donna M. Wilcock,Jorge Marcondes de Souza,Soniza Vieira Alves-Leon,Vania F. Prado,Marco A. M. Prado,Jose F. Abisambra,Fernanda Tovar-Moll,Paulo Mattos,Ottavio Arancio,Sergio T. Ferreira,Fernanda G. De Felice,Fernanda G. De Felice +28 more
TL;DR: FNDC5/irisin is placed as a novel agent capable of opposing synapse failure and memory impairment in AD, and restoration of its expression can ameliorate these phenotypes in rodent models.
Journal ArticleDOI
At the interface of sensory and motor dysfunctions and Alzheimer's disease
Mark W. Albers,Grover C. Gilmore,Jeffrey Kaye,Claire Murphy,Arthur Wingfield,David A. Bennett,Adam L. Boxer,Aron S. Buchman,Karen J. Cruickshanks,Davangere P. Devanand,Charles J. Duffy,Christine M. Gall,George A. Gates,Ann-Charlotte Granholm,Takao K. Hensch,Roee Holtzer,Bradley T. Hyman,Frank R. Lin,Ann C. McKee,John C. Morris,Ronald C. Petersen,Lisa C. Silbert,Robert G. Struble,John Q. Trojanowski,Joe Verghese,Donald A. Wilson,Shunbin Xu,Li I. Zhang +27 more
TL;DR: It is clear that sensory and motor regions of the central nervous system are affected by AD pathology and that interventions targeting amelioration of sensory‐motor deficits in AD may enhance patient function as AD progresses.
References
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