DZNE scientists receive funding from the US

The US Alzheimer’s Association is funding two research projects at DZNE’s Bonn site with a total of around 400,000 US dollars. The grants will finance projects by two early-career scientists.

Measuring aging: Aging is the primary risk factor for neurodegeneration and thus for Alzheimer’s disease and other dementias. Therefore, understanding aging at its roots – that is, at different molecular levels – is essential for developing strategies to prevent and treat dementia. In light of this, Dr. Dan Liu aims to unravel the microscopic mechanisms underlying age-related neurodegeneration in both women and men across their lifespan. This could result in the identification of targets for personalized, sex-specific prevention and treatment of dementias.

To this end, Dr. Liu will leverage state-of-the-art omics data from DZNE’s Rhineland Study, a population-based study involving more than 10,000 adults in Bonn, Germany. Thereby, she aims to generate a novel biological “aging metric” that, in contrast to established biological aging estimators, will assess aging at multiple molecular levels simultaneously. This would provide an unprecedentedly comprehensive and precise quantification of aging at the microscopic level. Importantly, she aims to use this tool to assess the relation of aging with neurodegenerative changes across the entire adult lifespan, which could disentangle the precise molecular mechanisms through which biological aging per se affects neurodegeneration.

“Not everyone ages the same way biologically. People of the same age can have very different experiences, if any, with neurodegeneration”, Dr. Liu says. “Therefore, I will be investigating how aging at the molecular levels is connected to neurodegeneration as we get older. The rationale behind this is to find new approaches for prevention and treatment.”

Trigger for dementia: Alzheimer’s disease is associated with chronic neuroinflammation, meaning that the brain’s immune system is in a permanent state of emergency. In particular, this applies to the microglia which are the nervous system’s resident immune cells. Although microglia can protect against Alzheimer’s pathology, and indeed do so initially, their functions are compromised as the disease progresses. Therefore, in the end, they do more harm than good. Conditions like obesity contribute to this neuroinflammation, although the molecular signals underlying these changes are unknown. Dr. Róisín McManus aims to investigate what triggers the microglia’s detrimental behavior, which could help identify new approaches for prevention and treatment.

To this end, she will study mouse models of Alzheimer’s disease and blood samples from people with and without Alzheimer’s. In addition, Dr. McManus will investigate iPSC-derived microglia obtained by reprogramming cells from patients; these could be from the skin, for example. In doing so, the focus will be on certain lipids that are changed during diet-induced obesity. This is because there is evidence that in obesity – a known risk factor for Alzheimer’s – specific lipids are increased and Dr. McManus’ data shows that they can act on the innate immune system, thus putting microglia into an active and ultimately deleterious state.

“This project bridges the molecular gap between Alzheimer’s disease and obesity by examining which precise lipids are the missing link and drive inflammation”, Dr. McManus says. “The outcomes could help find approaches to regulate neuroinflammation and thus combat dementia.”

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