Dural Ectopic Lymphatic Structures Accumulate During Aging and Are Dysregulated in Neurodegenerative Diseases

The meninges serve as an interface between the peripheral immune system and the central nervous system (CNS), playing a crucial role in maintaining parenchymal homeostasis. Neurodegenerative conditions, such as amyloidosis and tauopathies, are marked by extracellular neurotoxic amyloid-β (Aβ) plaques and intracellular tau tangles, both of which contribute to neuronal cell death and cognitive decline. The role of adaptive immunity in these pathologies remains debated, with studies suggesting it can either mitigate or exacerbate neuropathological progression. Ectopic lymphoid structures (ELS) resemble secondary lymphoid organs, form at sites of inflammation or pathology, and house adaptive immune cells. While ELSs can be beneficial in clearing infections or tumors, they may also have detrimental effects in certain pathological conditions. To explore the role of meningeal ELS in aging and CNS pathology, we analyzed the meninges of aged wild-type mice and mouse models of early-onset Alzheimer’s disease, tauopathy, and Down syndrome-related neurodegenerative disorders. Our findings suggest that the accumulation of dural ELS varies according to age, brain pathology, and sex. These results provide insight into the potential contribution of meningeal ELS to healthy aging and neurodegenerative conditions, offering new directions for future research.