Vascular dementia (VaD) and vascular cognitive impairment are conditions that result from cerebrovascular disease. VaD is considered as one of the most common causes for dementia after Alzheimer’s disease and the co-occurrence of vascular and Alzheimer’s pathology (Mixed Dementia) is frequent. Nevertheless, there is still no approved drug therapy available and the pathological mechanisms leading to cognitive decline are hardly understood. Additionally, the accurate identification of VaD patients for epidemiological research and clinical trials as well as trial monitoring is very challenging.

We hypothesize that Lipocalin2, a neutrophil gelatinase-associated protein that plays a role in innate immunity, is released form endothelial brain cells as a consequence of vascular damage, further released into the interstitial space, and therefore, specifically altered in the cerebrospinal fluid (CSF) of VaD cases. To this purpose CSF Lipocalin 2 will be evaluated in the differential context of neurodegenerative dementias as a potential diagnostic and prognostic marker of VaD. Associations with neuroimaging and biochemical biomarkers and, clinical data will be assessed in a retrospective cohort and in a prospective investigation. Findings will be validated in independent cohorts.

Additionally, we propose the study of human brain tissue in the spectrum of cerebrovascular pathologies (e.g. arteriosclerotic small vessel disease, large vessel disease, cerebral amyloid angiopathy) in order to shed light into the molecular mechanisms leading to altered Lipocalin 2 levels in VaD, which would also have benefits on setting the basis of drug trial monitoring.