Background
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, ImageJ 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

If you are interested in doing an internship with us, please contact us via mail: j.i.geertsema@uva.nl.