The effect of n-3 PUFA supplementation on amyloid load, microglial functioning and behavior in Alzheimer’s Disease

  • English language proficiency required
  • Amsterdam

SILS - University of Amsterdam

Alzheimer’s disease (AD) is a complex neurodegenerative disorder that involves not only amyloid pathology or neuroinflammation but also lipid alterations.
For instance, the frontal cortex of AD patients display abnormally low levels of n-3 polyunsaturated fatty acids (PUFAs). PUFAs and their derivatives play an important role in signalling. n-6 PUFAs derivatives are mostly involved in production of proinflammatory cytokines, meanwhile, n-3 PUFAs are metabolized to anti-inflammatory mediators, such as maresins, resolvins, and protectins. These specialized pro-resolving lipid mediators are produced during the resolution phase of inflammation and can modulate microglial activation and function. An enrichment of n-3 PUFAs during the development, e.g. through diet might be modulating microglial functioning, which could be beneficial for postponing the development of AD.

Here we study whether n-3 PUFAs could be used as an early (PND2-42) nutritional intervention from that could prime microglial cells, potentially delaying or ameliorating AD pathology and its cognitive defects. We assess the effect of n-3 PUFA supplementation on brain volume, amyloid load, microglial activation and its phagocytic properties, and cognitive functions in transgenic APP/PS1 mice.
Our findings 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.

The project:
The student will be involved in detailed analysis of microglia in close proximity versus distal to amyloid plaques.

Skills acquired:
– Immunocytochemistry
– 3D reconstruction of microglia
– Detailed morphological analysis of microglia
– Softwares such as Graphpad,┬áImageJ and Imaris

Depending on the skill and interest of the student, it is possible to expand the skills acquired, as multiple studies are running simultaneously.

Duration is flexible >4 months, start date between now and December 2023

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