title: Tau as the Converging Protein between Chronic Stress and Alzheimer's Disease Synaptic Pathology.
abstract: BACKGROUND
  Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder with a complex physiopathology and still undefined initiators. Several risk factors have been suggested for AD with recent evidence supporting an etiopathogenic role of chronic environmental stress and glucocorticoids (GCs, stress hormones) in the development of the disease. Indeed, both AD and chronic stress are associated with neuronal atrophy, synaptic loss and cognitive impairment. Our previous studies have demonstrated the aggravating role of stress and GCs on AD pathology, including Tau hyperphosphorylation and aggregation and cognitive deficits in various AD models. In light of the suggested involvement of Tau missorting in AD synaptotoxity and the dual cytoplasmic and synaptic role of Tau, our recent studies focused on the possible role of Tau in the underlying cascades of stress/GC neuronal malfunction/atrophy in wild-type animals by monitoring the intracellular localization of Tau and its phosphorylation status in different cellular compartments.
  
  
  CONCLUSIONS
  Biochemical, ultrastructural, behavioral and neurostructural analysis have helped demonstrate that prolonged GC administration leads to dendritic remodeling and spine atrophy and loss in the rat hippocampus triggering Tau missorting at hippocampal synapses with the participation of specific phosphorylated Tau isoforms in this synaptic accumulation.
  
  
  CONCLUSIONS
  The above findings suggest that Tau plays an essential role in mediating the neurodegenerative effects of stress and GCs towards the development of AD pathology. In addition, they highlight the involvement of Tau missorting in mechanism(s) of synaptic atrophy, beyond AD adding to our limited knowledge of the mechanisms through which stress causes brain pathology.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, and ICVS/3B's - PT Government Associate Laboratory, Braga, Portugal.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Sotiropoulos
authors.forename: Nuno
authors.initials: N
authors.lastname: Sousa
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002908:Chronic Disease; D006801:Humans; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D013569:Synapses / Q000378:metabolism* / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins