Early n-3 PUFA supplementation in a model for Alzheimer’s Disease

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Swammerdam Institute for Life Sciences - University of Amsterdam

Alzheimer’s disease (AD) is a complex neurodegenerative disorder that involves amyloid pathology, neuroinflammation and lipid alterations in the brain. Currently, no effective therapies or interventions exist to mitigate the effects of this disease. However, there is evidence suggesting that dietary polyunsaturated fatty acids (PUFAs) could potentially modify AD pathology. n-3 PUFAs and their derivatives are metabolized to specialized pro-resolving lipid mediators that can modulate microglial activation and function, in this way potentially modulating the progression of AD. Studies have shown that n-3 PUFAs, such as docosahexaenoic acid, may alleviate the burden of Aβ accumulation by enhancing microglial phagocytosis in vitro. In vivo, it has been demonstrated that a diet rich in n-3 PUFAs supplemented for more than a year Aβ in the brain and improved spatial memory in APP/PS1 mice. Here we study whether n-3 PUFAs could be used as an early nutritional intervention that could prime microglial cells, potentially delaying or ameliorating AD pathology and its cognitive defects, as previously we have shown the long-term effects of this early nutritional intervention on microglia and cognition of this diet in a different context, In this study, we supplement with a semi-synthetic diet supplemented with  N-3 PUFAs (LA/ALA=1) in a APP/PS1 mice from p2-42. We found no effects on behavior, but we found that amyloid was differentially phagocytosed in APP animals fed the N-3 PUFA rich diet.
Here, we will be assessing the neuropathological level by measuring amyloid load, hippocampus volume, microglial activation and its phagocytic properties by immunohistochemistry.
Our findings, of which the analyses are still ongoing, aim to shed light on whether an early dietary intervention supplemented with n-3 PUFAs could potentially modulate AD progression characterized by both behaviour and physiological markers later in life.

Skills acquired: Immunohistochemistry, (Confocal) imaging, image analysis with ImageJ and Imaris, Data analysis with Rstudio and Graphpad

To apply for this job email your details to j.i.geertsema@uva.nl