High Protein Diet Shrinks Brain in Alzheimer’s Disease Mice

Numerous epidemiological studies have suggested that a low-calorie, low-fat diet rich in vegetables, fruits, and fish could delay the onset or slow the progression of Alzheimer’s disease. Researchers have now tested the effects of several diets, head-to-head, for their effects on Alzheimer’s disease pathology in an Alzheimer’s mouse model. Although the study was focused on triggers for brain plaque formation, they unexpectedly found that a high protein diet apparently led to a smaller brain.

The image depicts the comparison of a normal aged brain (top) and an Alzheimer’s patient’s brain (bottom). Differential characteristics are pointed out.

The researchers tested four differing menus on a transgenic mouse model of Alzheimer’s disease, which express a mutant form of the human amyloid precursor protein (APP). APP’s role in the brain is not fully understood; however it is of great interest to Alzheimer’s disease researchers because the body uses it to generate the amyloid plaques typical of Alzheimer’s disease. These mice were fed either:

The researchers then looked at the brain and body weight of the mice, as well as plaque build up and differences in the structure of several brain regions that are involved in the memory defect underlying Alzheimer’s disease.

Mice fed a high protein/low carbohydrate diet had brains five percent lighter that all the others, and regions of their hippocampus were less developed. Until researchers test this effect on non-transgenic mice, it is unclear whether the loss of brain mass is associated with Alzheimer’s disease type plaque. But some studies in the published literature led the authors to put forward a tentative theory that a high protein diet may leave neurons more vulnerable to Alzheimer’s disease plaque. Mice on a high fat diet had raised levels of plaque proteins, but this had no effect on plaque burden.

Aside from transgenic mice, the pressing question is whether these data have implications for the human brain. “Given the previously reported association of high protein diet with aging-related neurotoxicity, one wonders whether particular diets, if ingested at particular ages, might increase susceptibility to incidence or progression of Alzheimer’s disease,” says lead author Sam Gandy. The only way to know for sure would require prospective randomized double blind clinical diet trials. According to Gandy, “This would be a challenging undertaking but potentially worthwhile. If there is a real chance that the ravages of Alzheimer’s disease might be slowed or avoided through healthy eating. Such trials will be required if scientists are ever to make specific recommendations about dietary risks for Alzheimer’s disease.”

References:
1. Sam Gandy, et al. Dietary composition modulates brain mass and amyloid beta levels in a mouse model of aggressive Alzheimer’s amyloid pathology. Molecular Neurodegeneration.