Characterization of non-human primate dura in health and neurodegeneration

Abstract

AbstractBrain meninges and associated vasculature participate in brain clearance and are implicated in many neurological conditions such as Alzheimer’s disease, meningitis, multiple sclerosis, stroke, and traumatic brain injury. However, most of our knowledge concerning brain clearance via meninges is based on rodent data, and relevance to human disease remains unclear. One of the technical barriers in studies of meningeal physiology in health and disease is that existing imaging modalities are suboptimal for large and optically non-transparent meningeal tissue of humans and non-human primate (NHP) animal models. To address this barrier, we performed first characterization of NHP dura by high resolution confocal microscopy of clarified tissue. We investigated vascular structures and resident cells in normal monkeys and primate models of tauopathy and synucleinopathy. We demonstrated the presence of an extensive meningeal vascular network covering the entire tissue surface with resolution to the smallest capillaries. This is also the first work to map lymphatic vessels in the dura of non-human primate (NHP). Overall, the NHP lymphatic meningeal system resembles the anatomy found in rat dura, but it is more complex. Analysis of dura from NPH models of tauopathy and synucleinopathy revealed an association with disease-specific biomarkers (amyloid, tau, α-synuclein) with both the blood and lymphatic vasculature. This work has broad relevance to many brain diseases where solute accumulation and abnormal macromolecular clearance is a part of the pathogenesis.