%A van Dijk,Gertjan %A van Heijningen,Steffen %A Reijne,Aaffien C. %A Nyakas,Csaba %A van der Zee,Eddy A. %A Eisel,Ulrich L. M. %D 2015 %J Frontiers in Neuroscience %C %F %G English %K Neuroinflammation,Obesity,type-2 diabetes mellitus,TNF,Blood-Brain Barrier,Alzheimers disease,Aging,Metabolic Syndrome X %Q %R 10.3389/fnins.2015.00173 %W %L %M %P %7 %8 2015-May-18 %9 Review %+ Gertjan van Dijk,Department Behavioural Neuroscience, Groningen Institute for Evolutionary Life Sciences, University of Groningen,Groningen, Netherlands,gertjan.van.dijk@rug.nl %# %! Filling in the dots between obesity and metabolic diseases towards AD %* %< %T Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration %U https://www.frontiersin.org/articles/10.3389/fnins.2015.00173 %V 9 %0 JOURNAL ARTICLE %@ 1662-453X %X Alzheimer's disease (AD) is a complex, multifactorial disease with a number of leading mechanisms, including neuroinflammation, processing of amyloid precursor protein (APP) to amyloid β peptide, tau protein hyperphosphorylation, relocalization, and deposition. These mechanisms are propagated by obesity, the metabolic syndrome and type-2 diabetes mellitus. Stress, sedentariness, dietary overconsumption of saturated fat and refined sugars, and circadian derangements/disturbed sleep contribute to obesity and related metabolic diseases, but also accelerate age-related damage and senescence that all feed the risk of developing AD too. The complex and interacting mechanisms are not yet completely understood and will require further analysis. Instead of investigating AD as a mono- or oligocausal disease we should address the disease by understanding the multiple underlying mechanisms and how these interact. Future research therefore might concentrate on integrating these by “systems biology” approaches, but also to regard them from an evolutionary medicine point of view. The current review addresses several of these interacting mechanisms in animal models and compares them with clinical data giving an overview about our current knowledge and puts them into an integrated framework.