title: Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration.
abstract: 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.
authors.affiliation: Department Behavioural Neuroscience, Groningen Institute for Evolutionary Life Sciences, University of Groningen Groningen, Netherlands.
authors.forename: Gertjan
authors.initials: G
authors.lastname: van Dijk
authors.affiliation: Department Behavioural Neuroscience, Groningen Institute for Evolutionary Life Sciences, University of Groningen Groningen, Netherlands.
authors.forename: Steffen
authors.initials: S
authors.lastname: van Heijningen
authors.affiliation: Department Behavioural Neuroscience, Groningen Institute for Evolutionary Life Sciences, University of Groningen Groningen, Netherlands ; Systems Biology Centre for Energy Metabolism and Ageing, University Medical Center, University of Groningen Groningen, Netherlands.
authors.forename: Aaffien C
authors.initials: AC
authors.lastname: Reijne
authors.affiliation: Department Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences, University of Groningen Groningen, Netherlands.
authors.forename: Csaba
authors.initials: C
authors.lastname: Nyakas
authors.affiliation: Department Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences, University of Groningen Groningen, Netherlands.
authors.forename: Eddy A
authors.initials: EA
authors.lastname: van der Zee
authors.affiliation: Department Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences, University of Groningen Groningen, Netherlands ; University Centre of Psychiatry, University Medical Center Groningen, University of Groningen Groningen, Netherlands.
authors.forename: Ulrich L M
authors.initials: UL
authors.lastname: Eisel
keywords: Alzheimer's disease; TNF; aging; blood-brain barrier; metabolic syndrome; neuroinflammation; obesity; type-2 diabetes mellitus