Neuroinflammation in Alzheimer disease

Abstract

Increasing evidence points to a pivotal role of immune processes in the pathogenesis of Alzheimer disease, which is the most prevalent neurodegenerative and dementia-causing disease of our time. Multiple lines of information provided by experimental, epidemiological, neuropathological and genetic studies suggest a pathological role for innate and adaptive immune activation in this disease. Here, we review the cell types and pathological mechanisms involved in disease development as well as the influence of genetics and lifestyle factors. Given the decade-long preclinical stage of Alzheimer disease, these mechanisms and their interactions are driving forces behind the spread and progression of the disease. The identification of treatment opportunities will require a precise understanding of the cells and mechanisms involved as well as a clear definition of their temporal and topographical nature. We will also discuss new therapeutic strategies for targeting neuroinflammation, which are now entering the clinic and showing promise for patients. This Review provides an in-depth examination of how inflammation contributes to neurodegeneration in Alzheimer disease. The authors explore the impact of extrinsic factors, such as brain trauma, diet and infections, and host-intrinsic factors, such as the activity of microglial cells and other immune, vascular and neuronal cell populations, on disease development. They also highlight emerging drugs that target this inflammatory component for therapy of Alzheimer disease.