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

  1. Leonard Petrucelli
  1. Department of Neuroscience, Mayo Clinic Florida, Jacksonville, Florida
  1. Corresponding author: Leonard Petrucelli, petrucelli.leonard{at}mayo.edu.

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 (35).

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 …

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