Brain microbleeds and Alzheimer's disease: innocent observation or key player?

Brain microbleeds are small dot-like lesions appearing as hyposignals on gradient echo magnetic resonance sequences. In Alzheimer's disease, brain microbleeds are of special interest as they may play a crucial role in the pathophysiology. They may be a missing link between two important theories on the neuropathogenesis of Alzheimer's disease-the amyloid cascade hypothesis and the vascular hypothesis. Moreover, they may affect the clinical course of the disease and may have therapeutic consequences. The aim of this article is to review available data to understand the meaning of brain microbleeds in clinical terms and underlying pathology in the context of Alzheimer's disease. We also review the available evidence and highlight the pitfalls of our current knowledge on brain microbleeds in the setting of clinical trials design.