Deciphering the Role of Oligodendrocytes in the Pathogenesis of Alzheimer’s Disease

• Applicant: Dr. Sarah Jaekel
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 447473440

Cortical myelination inversely reflects the pathology of Alzheimer’s Disease (AD) with late myelinating regions being early affected and vice versa. This pathological observation made by the Braaks, has been little explored but invokes the hypothesis that oligodendrocytes - the myelinating cells of the central nervous system - are actively involved in the pathogenesis of AD. Although AD has been mostly considered a neuronal pathology, there is accumulating evidence that the observed oligodendrocyte pathology is more than a bystander effect. My recently published and preliminary work on human oligodendrocyte heterogeneity suggests that there are underlying functional differences between oligodendrocyte states and that a heterogeneous distribution of these may explain the variable vulnerability of different cortical areas to AD pathology. This hypothesis forms the core of my research proposal that uses a combination of cutting-edge single nuclei RNA-sequencing technologies, in vitro and in vivo approaches to address this gap of knowledge. This innovative and multidisciplinary project will unravel functional differences in oligodendrocyte states and determine how a skew in these states contributes to AD pathogenesis. It will be carried out within an internationally leading neuroscience research hub at the Center for Stroke and Dementia in Munich with collaborations with internationally renowned experts both in AD and oligodendrocyte research and will help me to successfully establish myself as an independent group leader in this research field.

• DFG Programme: Independent Junior Research Groups