Deciphering bAD microglia in Alzheimer’s diseases

Alzheimer’s disease (AD) development is connected to microglia, the inflammatory cell of the brain, and ageing is the strongest risk factor. Microglia is found around the Aβ plaque. We have identified galectin-3 in microglia, related to neurodegeneration. The ApoE gene (20% frequency) is another strong risk factor where the ApoE4 variant increase the risk several-fold.

Recent data have identified ApoE as key signaling in AD-activated microglia and this signaling also involve galectin-3.

Microglia are suggested to also be involve in the spreading of detrimental tau that is believed to spread between neurons.Our hypothesis is that early microglia activation leads to a destructive inflammation and dysfunction of microglia phenotype that will be detrimental for the neurons.

Objectives:-How does the microglia-specific protein gal3 lead to aggressive activation of microglia and affect tau spreading?-Is the detrimental activation of microglia affected by the ApoE genotype and age?We study cell and mouse models of AD, incl special ApoE mice, as well as brain material from deceased patients and examination of spinal fluid from patients.

We use standard techniques but also advanced synchrotron-based spectroscopy (FTIR, MAX 4 Lab), microscopy (e.g.

CLEM) and single cell transcriptomics (scRNAseq) for identifying microglia phenotype.We believe that understanding microglial activation can alleviate AD pathology and may be relevant to future treatment strategies.