Does Obesity-Induced τ Phosphorylation Tip the Scale Toward Dementia?

Abstract

Obesity, a worldwide epidemic with numerous health implications, is gaining traction as a risk factor for dementia. The need for research is evident: at least 2.8 million obese or overweight adults die each year according to the World Health Organization, and more than two-thirds of American adults are overweight or obese (1). Obesity increases the risk of several health conditions, including hypertension, dyslipidemia, insulin resistance, and type 2 diabetes (2). In addition, obesity, as well as type 2 diabetes, increases the risk of cognitive dysfunction and dementia (3–5). In this issue of Diabetes , Leboucher et al. (6), provide evidence that aberrant phosphorylation of the protein τ is a molecular link between obesity and impaired memory. In fact, much evidence supports the notion that τ dysfunction plays a central role in cognitive deficits. For example, intracellular neurofibrillary tangles composed of hyperphosphorylated τ are a neuropathological hallmark of Alzheimer’s disease, the most common form of dementia. Moreover, the number of τ-containing neurofibrillary tangles in the neocortex of the brain in Alzheimer’s disease positively correlates with severity of cognitive decline (7), and mutations in MAPT , the gene encoding τ, have been shown to cause frontotemporal dementia (8,9). To gain a better understanding of the mechanisms by which obesity increases the risk of dementia, Leboucher et al. investigated the effects of diet-induced …