Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease 1.0.0

By contrast, the parenchyma of the CNS is devoid of lymphatic vasculature2; in the brain, removal of cellular debris and toxic molecules, such as amyloid-β peptides, is mediated by a combination of transcellular transport mechanisms across the blood−brain and blood−cerebrospinal fluid (CSF) barriers7–9, phagocytosis and digestion by resident microglia and recruited monocytes and/or macrophages10,11, as well as CSF influx and ISF efflux through a paravascular (glymphatic) route12–14 PubMed:30046111

Analysis of lymphoid and myeloid cell populations in the meninges (Extended Data Fig. 9d) demonstrated a significant increase in the number of macrophages upon lymphatic ablation compared to both control groups (Extended Data Fig. 9e), which might be correlated with increased amyloid-β deposition and inflammation in the meninges PubMed:30046111

Staining for amyloid-β in the brains of nine patients with Alzheimer’s disease and eight controls without Alzheimer’s disease (Extended Data Table 1) revealed, as expected, marked parenchymal deposition of amyloid-β in the brains of patients with Alzheimer’s disease, but not in the brains of the controls without Alzheimer’s disease (Extended Data Fig. 9l, m) PubMed:30046111

Notably, when compared to tissue from controls, all samples from patients with Alzheimer’s disease demonstrated striking vascular amyloid-β pathology in the cortical leptomeninges (Extended Data Fig. 9l, m) and amyloid-β deposition in the dura mater adjacent to the superior sagittal sinus (Fig. 3i, j) or further away from the sinus (Fig. 3k, l) PubMed:30046111

These findings showed that prominent meningeal amyloid-β deposition observed in patients with Alzheimer’s disease is also observed in mouse models of Alzheimer’s disease after meningeal lymphatic vessel ablation PubMed:30046111