Tau is a protein mainly involved in the stabilization of the neuronal skeleton. The function of tau is regulated by the attachment of phosphate groups (phosphorylation) that occur in specific sites of the protein. In Alzheimer’s disease (AD), neuronal tau protein is hyperphosphorylated and aggregates to form one of the major pathological features of the disease, the neurofibrillary tangles (brain tangles). Previous studies have shown that chronic obesity and diabetes are associated with AD and may impair the central nervous system function. Difficulties in effective insulin use (i.e., impaired glucose absorption by the cells) have also been found in post-mortem brains of people with AD and could be associated to the phosphorylation state of neuronal tau protein. However, the impact of fatty foods on cognitive function and mood in a mouse model for AD predisposed to memory problems and pronounced tau hyperphosphorylation is still unknown. In a new study published in the journal Metabolic Brain Disease, the team of researchers led by Jing Xiong and Xin-Fu Zhou from the University of South Australia (Adelaide, Australia) found a clear association among long-term high fat diet and the exacerbation of cognitive decline.
To understand the impacts of fatty food on cognitive function, the researchers of the study used a mouse model for AD with a pronounced phosphorylation of tau protein. Mice were either fed a standard diet or a high fat diet for 30 weeks. Variations in food energy intake, body weight, glucose levels and insulin tolerance were measured. Anxiety, depression, memory, and tau phosphorylation state were also assessed at different intervals of the study. The researchers showed that long-term high fat diet enhances body weight gain and caloric intake, that are larger in the AD mouse model. Fatty food induces obesity, impaired insulin sensitivity and altered glucose absorption. It also aggravates anxiety and depression, as well as tau hyperphosphorylation, and cognitive impairment in mice with memory problems and pronounced tau pathology. These findings reveal that a high fat diet not only induces obesity, but also leads to diabetes, cognitive impairment and behavioural changes in mice predisposed to brain tangles and cognitive decline. The study also highlights the effects of metabolic syndromes and tau pathology on mood and cognitive behaviour, and points towards a mouse model that may be beneficial to study the link between and mechanisms of AD, diabetes and obesity.
https://link.springer.com/article/10.1007/s11011-022-01029-x
