Salta group

General description research

The overarching question of our research is whether the degenerating brain can repair itself to delay or counteract cognitive decline in conditions like Alzheimer’s disease (AD). We profile the multicellular complexity of Alzheimer’s pathophysiology and dissect how specific genes and cellular mechanisms may enhance the overall fitness of the brain’s microenvironment by repairing or “rejuvenating” the AD brain. We integrate approaches involving postmortem human brain, ‘humanized’ mouse models, human iPSC-derived 2D and 3D cultures, cutting-edge single-cell omics technologies, and advanced, tailored experimental and computational pipelines.

Psychiatric symptoms (or disorders) the group is interested in

We are interested in the neuropsychiatric symptoms that are observed in the majority of AD patients, including depression, anxiety, agitation, aggression, and apathy. In addition, we consider psychotic symptoms, including delusions and hallucinations, that can be observed in approximately half of the patients. As a member of the iCNS Gravitation consortium, we are also more broadly interested in the molecular basis of depression, anxiety and psychosis.

Technical approaches

We make use of the exceptionally well documented brain donor collection of the Netherlands Brain Bank to identify and stratify postmortem human brain according to strictly pre-defined clinicopathological selection criteria. Subsequently, we employ single-cell omics technologies to generate molecular and cellular human brain atlases. We use human induced pluripotent stem cells (iPSC)-derived cell cultures to functionally validate prioritized targets obtained from the postmortem human brain datasets. Eventually, we aim to identify molecular and cellular signatures that are highly correlated to psychiatric and other symptoms, and which can be employed as predictive or therapeutic targets.

Keywords: Human brain, human iPSCs, single-cell omics

List of  the matching research domains and/or disorders: Cognitive systems: Declarative memory, Cognitive control, Working memory