The locus coeruleus:
at the crossroad of dementia syndromes

Objectives

1

The aim is to characterize LC degeneration, noradrenergic dysfunction and their impact on target brain areas, and to establish whether changes in blood/CSF biomarkers of noradrenergic neuronal loss are associated with dementia across the different neurodegenerative disorders. We combine comprehensive studies in post-mortem brains, PET imaging, blood/CSF biomarkers and iPSCs across DS, AD and PD.

2

The aim is to characterize noradrenergic neurodegeneration and endo-lysosomal alterations in the LC in DS, AD and PD rodent models. Since LC degeneration and noradrenergic function disturbances are early events in AD, DS and PD, mouse models of the three disorders are useful to analyse the noradrenergic neurodegeneration progression and its specific relationship with other neuropathological signs and behavioural and cognitive changes.

3

The aim is to explore the role of genes mapping to HSA21 in dementia-associated noradrenergic deafferentation. DS candidate genes such as DYRK1A and APP interact with signalling pathways and genes relevant to AD pathogenesis. In addition, overexpression of these genes induces alterations in noradrenergic profiles. We analyse the involvement of DYRK1A and APP in noradrenergic degeneration in the AD, DS and PD mouse models