Functional networks supporting cognitive resilience

Cognitive resilience designates the ability to show disproportional high levels of cognitive function despite substantial brain pathology. Cognitive resilience is an important factor slowing down the development of dementia in AD, but the underlying mechanism are not well understood. To address that question, we focus on the topological characteristics of the functional connectome of the brain that underly resilience. Using graph theoretical analyses, we identified hub connectivity in the fronto-parietal control network (Neitzel et al. 2019) as well as higher segregation of functional networks (Franzmeier et al. Brain, in press) as key neural substrates supporting cognitive resilience against pathologic tau.

The role of TREM2-related microglia activation in Alzheimer’s

Rare loss-of-function mutations in the gene encoding TREM2, i.e. a receptor molecular expressed by microglia, are associated with a dramatic increase in the risk of AD. Together with our collaborator Prof. Christian Haass (DZNE, Munich), we found changes in biofluid levels of soluble TREM2 protein occur up to 5 years before the onset of AD dementia (Suarez-Calvet, Science Trans Med, 2016), consistent with a microglia response triggered by AD pathology. Importantly, higher biomarker levels of sTREM2 at a given level of beta-amyloid and tau pathology were associated with slower subsequent cognitive decline (Ewers et al. Science Transl Medicine 2019), reduced detrimental effects of ApoE e3 genotype (Franzmeier et al. Mol Neurodeg. 2020) and slower rate of increase in amyloid PET (Ewers et al. EMBO Mol Med. 2020).