The locus coeruleus:
at the crossroad of dementia syndromes

Background

The loss of Locus Coeruleus (LC) noradrenergic neurons is one of the first pathophysiological sign in Parkinson’s disease (PD) and a major feature of Alzheimer’s disease (AD) and Down syndrome (DS). However, the shared mechanisms and pathways through which LC projection neurons degenerate in these three neurodegenerative disorders are not well understood.

Objective

HEROES’s goal is to uncover underlying pathogenic mechanisms, and explore these as potentially common pathways in AD, DS and PD and their therapeutic relevance.

Approach

HEROES will characterize noradrenergic neurodegeneration in AD, DS and PD using post-mortem brain material, iPSC-derived neurons and neuroimaging from patients.

Findings will be validated in mouse models of these diseases. The project will focus also on the involvement of specific chromosome 21 genes in AD, DS and PD pathways.

Expected achievements

  • New knowledge about common molecular, cellular and pathophysiological mechanisms in DS, AD and PD.
  • New molecular, neuroimaging and cognitive biomarkers across our target diseases.
  • Bio-repositories (human samples and iPSCs) for further research.
  • New molecular targets for common therapy for patients affected by DS, AD and PD.

Impact

HEROES will impact on clinical diagnosis, and also provide important information on biomarkers of dementia progression that will be valuable for prognosis and future clinical studies. In addition, HEROES will improve knowledge of common mechanisms and pathways of degeneration, which could help to identify new treatment strategies.