MINIALZ - Microglia-neuron interaction in Alzheimer’s disease: bridging from basic research to clinical applications for diagnostics and therapy - LCSB

The aim of this project is to give important indications for earlier diagnosis and potential treatment options to help address Alzheimer’s disease.

The project at a glance

Start date:

01 Jan 2023
Duration in months:

1
Funding:

Luxembourg National Research Fund (FNR)
Principal Investigator(s):

Michael Heneka

Jens KREISEL

Anne GRÜNEWALD

Martin Kampmann (external)

Stefan Beyenburg (external)

Guy Berchem (external)

About

Dementia has been identified by the Word Health Organisation as a major and global health issue since 2012. Indeed, we expect an increase from currently 55 million dementia cases to about 150 million in 2050. Approximately two thirds of all dementia patients suffer from Alzheimer’s disease (AD), a neurodegenerative disorder that leads to memory dysfunction, behavioural disturbances and loss of all higher cognitive functions.

It has increasingly become clear that Alzheimer’s is in fact not a disease of the elderly but starts much earlier in life. Understanding its origins is therefore key to be able to detect and treat it before the devastating effects on the brain fully appear. To date, the pathogenesis of AD remains unclear and neither a preventive, disease-modifying or acute therapy exists.

MINIALZ aims to study the interaction of immune cells and neurons in the brain and to identify molecular mechanisms that can be harnessed for developing new therapeutic avenues for the treatment of AD. MINIALZ will further identify early immune function and biomarker traits, to support diagnosis prior to clinical appearance. MINIALZ will be based on a new mechanism recently identified by the Neuroinflammation research group, by which microglia form a tunnelling nanotube network (TNTs) with neighboring neurons to free the latter from pathological proteins and ensure their function and survival. Preliminary data suggest that such microglia-neuron TNTs may contribute to neuronal survival in models of neurodegeneration and the involved mechanisms are defective in microglia carrying disease-associated AD risk mutations.

These findings are entirely new and place TNTs at the core of neurodegenerative disease pathogenesis. Further studies detailing the underlying molecular mechanisms and most likely their role for other CNS disorders such as Multiple Sclerosis, stroke, or brain trauma may soon follow.