Disentangling the Role of Intracranial Arteriosclerosis in Alzheimer’s Disease

Vascular disease is an important risk factor for dementia, often contributing in conjunction with Alzheimer’s pathology (like amyloid beta and tau) to the clinical phenotype of Alzheimer’s disease (AD). Yet, the exact role of vascular disease in brain health and the development of clinical AD, and its interaction with hallmark AD pathology, remains largely unknown. The current research project will provide insight into the role of arteriosclerosis—a hallmark of vascular disease—in AD, with a particular focus on the intracranial vasculature and the earliest form of disease, by using an innovative, population imaging-based approach. The Rotterdam Study is a large, population-based cohort study in which the development of many age-related diseases such as AD is studied prospectively. All participants in the study are ages 40 or older and regularly undergo a broad spectrum of examinations, such as physical examinations, blood sampling and interviews, to get a thorough impression of their health. The current study will wield data from two specific subsamples of the Rotterdam Study, in which computed tomography (CT) scans, positron emission tomography (PET) scans and magnetic resonance imaging (MRI) scans were made to 1) visualize arteriosclerosis in the brain, 2) visualize the presence and severity of amyloid beta depositions in the brain, and 3) measure pathology in and the function of the smallest blood vessels in the brain.

Together with the wealth of information from the Rotterdam Study on lifestyle, genetics, clinical risk factors and the occurrence of dementia, this will provide crucial novel insight into the role of arteriosclerosis in the development of AD. Ultimately, the results of the studies from this proposal may contribute to the development of therapeutic and preventive strategies for AD and dementia at large by targeting arteriosclerosis through novel therapies.