Inflammatory networks that mediate cognitive decline in Alzheimer’s Disease

Age-related diseases, such as Alzheimer’s disease (AD), are defining public health concerns of the 21st century and are the leading cause of disability worldwide. A growing body of evidence notes that central nervous system immune changes superimposed on ongoing chronic neurodegeneration may have a major impact on disease progression in AD and other neurodegenerative conditions. The role of the peripheral immune system in AD, including cellular elements of both the innate and adaptive immunity are still enigmatic. In collaboration with the Cleveland Alzheimer’s disease Research Center Luo Ruvo Center for Brain health we investigate immune cell identity and abundance in the periphery and cerebrospinal fluid (CSF) at single cell resolution among preclinical-AD, MCI-AD, and AD-Dementia stages and among normal aging controls. Our studies corroborate the severity of blood brain barrier (BBB) changes associated with specific immune cell profiles noted in CSF and the periphery across AD stages and its impact on longitudinal cognitive decline. The overall goal of this work is to characterize immune cell identity and abundance in the periphery and the CNS at single cell resolution across different AD clinical stages and in tandem, to clarify the peripheral anatomical context of immune cell activation and the degree of BBB changes. Success will help elucidate a better understanding of the temporal course of immune response in relation to initiation of clinical decline and subsequent phenotypic heterogeneity of AD trajectories.