GBD 2016 Neurology Collaborators. Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 18, 459–480 (2019).

Article  Google Scholar 

De Angelis, F., John, N. A. & Brownlee, W. J. Disease-modifying therapies for multiple sclerosis. BMJ 363, k4674 (2018).

Article  Google Scholar 

International Multiple Sclerosis Genetics Consortium. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science 365, eaav7188 (2019).

Article  Google Scholar 

International Multiple Sclerosis Genetics Consortium; MultipleMS Consortium. Locus for severity implicates CNS resilience in progression of multiple sclerosis. Nature 619, 323–331 (2023).

Article  Google Scholar 

Gusev, A. et al. Partitioning heritability of regulatory and cell-type-specific variants across 11 common diseases. Am. J. Hum. Genet. 95, 535–552 (2014).

Article  CAS  Google Scholar 

Maurano, M. T. et al. Systematic localization of common disease-associated variation in regulatory DNA. Science 337, 1190–1195 (2012).

Article  CAS  Google Scholar 

Chun, S. et al. Limited statistical evidence for shared genetic effects of eQTLs and autoimmune-disease-associated loci in three major immune-cell types. Nat. Genet. 49, 600–605 (2017).

Article  CAS  Google Scholar 

Yazar, S. et al. Single-cell eQTL mapping identifies cell type-specific genetic control of autoimmune disease. Science 376, eabf3041 (2022).

Article  CAS  Google Scholar 

Schmiedel, B. J. et al. Single-cell eQTL analysis of activated T cell subsets reveals activation and cell type-dependent effects of disease-risk variants. Sci. Immunol. 7, eabm2508 (2022).

Article  CAS  Google Scholar 

Hollenbach, J. A. et al. A specific amino acid motif of HLA-DRB1 mediates risk and interacts with smoking history in Parkinson’s disease. Proc. Natl Acad. Sci. USA 116, 7419–7424 (2019).

Article  CAS  Google Scholar 

Nalls, M. A. et al. Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet Neurol. 18, 1091–1102 (2019).

Article  CAS  Google Scholar 

Foo, J. N. et al. Identification of risk loci for Parkinson disease in Asians and comparison of risk between Asians and Europeans: a genome-wide association study. JAMA Neurol. 77, 746–754 (2020).

Article  Google Scholar 

Yu, E. et al. Machine learning nominates the inositol pathway and novel genes in Parkinson’s disease. Brain 147, 887–899 (2023).

Article  Google Scholar 

Beilina, A. et al. Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease. Proc. Natl Acad. Sci. USA 111, 2626–2631 (2014).

Article  CAS  Google Scholar 

Diaz-Ortiz, M. E. et al. GPNMB confers risk for Parkinson’s disease through interaction with α-synuclein. Science 377, eabk0637 (2022).

Article  CAS  Google Scholar 

Frischer, J. M. et al. Clinical and pathological insights into the dynamic nature of the white matter multiple sclerosis plaque. Ann. Neurol. 78, 710–721 (2015).

Article  Google Scholar 

Kutzelnigg, A. et al. Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 128, 2705–2712 (2005).

Article  Google Scholar 

iMSMS Consortium. Gut microbiome of multiple sclerosis patients and paired household healthy controls reveal associations with disease risk and course. Cell 185, 3467–3486.e16 (2022).

Article  Google Scholar 

Tan, A. H., Lim, S. Y. & Lang, A. E. The microbiome-gut-brain axis in Parkinson disease — from basic research to the clinic. Nat. Rev. Neurol. 18, 476–495 (2022).

Article  Google Scholar 

Yang, C. et al. Immunoglobulin A antibody composition is sculpted to bind the self gut microbiome. Sci. Immunol. 7, eabg3208 (2022).

Article  CAS  Google Scholar 

Rustenhoven, J. & Kipnis, J. Brain borders at the central stage of neuroimmunology. Nature 612, 417–429 (2022).

Article  CAS  Google Scholar 

Fitzpatrick, Z. et al. Gut-educated IgA plasma cells defend the meningeal venous sinuses. Nature 587, 472–476 (2020).

Article  CAS  Google Scholar 

Howell, O. W. et al. Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis. Brain 134, 2755–2771 (2011).

Article  Google Scholar 

Magliozzi, R. et al. Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain 130, 1089–1104 (2007).

Article  Google Scholar 

Serafini, B., Rosicarelli, B., Magliozzi, R., Stigliano, E. & Aloisi, F. Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol. 14, 164–174 (2004).

Article  Google Scholar 

Pikor, N. B. et al. Integration of Th17- and lymphotoxin-derived signals initiates meningeal-resident stromal cell remodeling to propagate neuroinflammation. Immunity 43, 1160–1173 (2015).

Article  CAS  Google Scholar 

Calabrese, M. et al. The changing clinical course of multiple sclerosis: a matter of gray matter. Ann. Neurol. 74, 76–83 (2013).

Article  Google Scholar 

Zuo, M. et al. Age-dependent gray matter demyelination is associated with leptomeningeal neutrophil accumulation. JCI Insight 7, e158144 (2022).

Article  Google Scholar 

Graves, J. S. et al. Ageing and multiple sclerosis. Lancet Neurol. 22, 66–77 (2023).

Article  Google Scholar 

Macaron, G. et al. Impact of aging on treatment considerations for multiple sclerosis patients. Front. Neurol. 14, 1197212 (2023).

Article  Google Scholar 

Sampson, T. R. et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell 167, 1469–1480 (2016).

Article  CAS  Google Scholar 

Vijiaratnam, N., Simuni, T., Bandmann, O., Morris, H. R. & Foltynie, T. Progress towards therapies for disease modification in Parkinson’s disease. Lancet Neurol. 20, 559–572 (2021).

Article  CAS  Google Scholar 

Jenner, P. Functional models of Parkinson’s disease: a valuable tool in the development of novel therapies. Ann. Neurol. 64, S16–S29 (2008).

Article  CAS  Google Scholar 

Lodygin, D. et al. β-Synuclein-reactive T cells induce autoimmune CNS grey matter degeneration. Nature 566, 503–508 (2019).

Article  CAS  Google Scholar 

Atkinson, J. R. et al. Biological aging of CNS-resident cells alters the clinical course and immunopathology of autoimmune demyelinating disease. JCI Insight 7, e158153 (2022).

Article  Google Scholar 

Matheoud, D. et al. Intestinal infection triggers Parkinson’s disease-like symptoms in Pink1−/− mice. Nature 571, 565–569 (2019).

Article  CAS  Google Scholar 

Najm, F. J. et al. Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo. Nature 522, 216–220 (2015).

Article  CAS  Google Scholar 

James, O. G. et al. iPSC-derived myelinoids to study myelin biology of humans. Dev. Cell 56, 1346–1358.e6 (2021).

Article  CAS  Google Scholar 

Madhavan, M. et al. Induction of myelinating oligodendrocytes in human cortical spheroids. Nat. Methods 15, 700–706 (2018).

Article  CAS  Google Scholar 

Okuda, D. T. et al. Incidental MRI anomalies suggestive of multiple sclerosis: the radiologically isolated syndrome. Neurology 72, 800–805 (2009).

Article  CAS  Google Scholar 

Amato, M. P. et al. Association of MRI metrics and cognitive impairment in radiologically isolated syndromes. Neurology 78, 309–314 (2012).

Article  CAS  Google Scholar 

Bonzano, L. et al. Subclinical motor impairment assessed with an engineered glove correlates with magnetic resonance imaging tissue damage in radiologically isolated syndrome. Eur. J. Neurol. 26, 162–167 (2019).

Article  CAS