title: Temperature and toxic Tau in Alzheimer's disease: new insights.
abstract: Alzheimer's disease (AD), the most common dementia in the elderly, is characterized by cognitive impairment and severe autonomic symptoms such as disturbance in core body temperature (Tc), which may be predictors or early events in AD onset. Inclusions of phosphorylated Tau (p-Tau) are a hallmark of AD and other neurodegenerative disorders called "Tauopathies." Animal and human studies show that anesthesia augments p-Tau levels through reduction of Tc, with implications for AD. Additionally, hypothermia impairs memory and cognitive function. The molecular networks related to Tc that are associated with AD remain poorly characterized. Under physiological conditions, Tau binds microtubules, promoting their assembly and stability. The dynamically regulated Tau-microtubule interaction plays an important role in structural remodeling of the cytoskeleton, having important functions in neuronal plasticity and memory in the hippocampus. Hypothermia-induced increases in p-Tau levels are significant, with an 80% increase for each degree Celsius below normothermic conditions. Although the effects of temperature on Tau phosphorylation are evident, its effects on p-Tau degradation remain poorly understoodWe review information concerning the mechanisms of Tau regulation of neuron plasticity via its effects on microtubule dynamics, with focus on pathways regulating the abundance of phosphorylated Tau species.  We highlight the effects of temperature on molecular mechanisms influencing the development of Tau-related diseases. Specifically, we argue that cold might preferentially affects central nervous system structures that are highly reliant upon plasticity, such as the hippocampus, and that the effect of cold on Tau phosphorylation may constitute a pathology-initiating trigger leading to neurodegeneration.
authors.affiliation: Graduate Program in Neuroscience and Cognition; Universidade Federal do ABC; São Bernardo do Campo, Brasil; Center for Natural Sciences and Humanities; Universidade Federal do ABC; São Bernardo do Campo, Brasil.
authors.forename: Daniel Carneiro
authors.initials: DC
authors.lastname: Carrettiero
authors.affiliation: Graduate Program in Neuroscience and Cognition; Universidade Federal do ABC; São Bernardo do Campo , Brasil.
authors.forename: Fernando Enrique
authors.initials: FE
authors.lastname: Santiago
authors.affiliation: Graduate Program in Neuroscience and Cognition; Universidade Federal do ABC; São Bernardo do Campo , Brasil.
authors.forename: Anna Carolina Parracho
authors.initials: AC
authors.lastname: Motzko-Soares
authors.affiliation: Graduate Program in Neuroscience and Cognition; Universidade Federal do ABC; São Bernardo do Campo, Brasil; Center for Natural Sciences and Humanities; Universidade Federal do ABC; São Bernardo do Campo, Brasil.
authors.forename: Maria Camila
authors.initials: MC
authors.lastname: Almeida
keywords: Alzheimer's disease; brain plasticity; hippocampus; hypothermia; memory and degradation; microtubule dynamics; tauopathy; temperature