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Review

The Role of Microglia in Inherited White-Matter Disorders and Connections to Frontotemporal Dementia

, &
Pages 195-207 | Published online: 31 Mar 2021

References

  • van der Knaap MS, Bugiani M. Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms. Acta Neuropathol (Berl). 2017;134(3):351–382. doi:10.1007/s00401-017-1739-1
  • van der Knaap MS, Bugiani M. Leukodystrophies - much more than just diseases of myelin. Nat Rev Neurol. 2018;14(12):747–748. doi:10.1038/s41582-018-0093-9
  • van der Knaap MS, Schiffmann R, Mochel F, Wolf NI. Diagnosis, prognosis, and treatment of leukodystrophies. Lancet Neurol. 2019;18(10):962–972. doi:10.1016/S1474-4422(19)30143-7
  • Schiller S, Henneke M, Gärtner J. Opening new horizons in the treatment of childhood onset leukodystrophies. Neuropediatrics. 2019;50(4):211–218. doi:10.1055/s-0039-1685529
  • Helman G, Venkateswaran S, Vanderver A. The spectrum of adult-onset heritable white-matter disorders. Handb Clin Neurol. 2018;148:669–692. doi:10.1016/B978-0-444-64076-5.00043-0
  • Lynch DS, Wade C, de Paiva ARB, et al. Practical approach to the diagnosis of adult-onset leukodystrophies: an updated guide in the genomic era. J Neurol Neurosurg Psychiatry. 2019;90(5):543–554. doi:10.1136/jnnp-2018-319481
  • Prinz M, Priller J. Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease. Nat Rev Neurosci. 2014;15(5):300–312. doi:10.1038/nrn3722
  • Li Q, Barres BA. Microglia and macrophages in brain homeostasis and disease. Nat Rev Immunol. 2018;18(4):225–242. doi:10.1038/nri.2017.125
  • Song WM, Colonna M. The identity and function of microglia in neurodegeneration. Nat Immunol. 2018;19(10):1048–1058. doi:10.1038/s41590-018-0212-1
  • Kao AW, McKay A, Singh PP, Brunet A, Huang EJ. Progranulin, lysosomal regulation and neurodegenerative disease. Nat Rev Neurosci. 2017;18(6):325–333. doi:10.1038/nrn.2017.36
  • Paushter DH, Du H, Feng T, Hu F. The lysosomal function of progranulin, a guardian against neurodegeneration. Acta Neuropathol (Berl). 2018;136(1):1–17. doi:10.1007/s00401-018-1861-8
  • Lui H, Zhang J, Makinson SR, et al. Progranulin deficiency promotes circuit-specific synaptic pruning by microglia via complement activation. Cell. 2016;165(4):921–935. doi:10.1016/j.cell.2016.04.001
  • Krabbe G, Minami SS, Etchegaray JI, et al. Microglial NFκB-TNFα hyperactivation induces obsessive-compulsive behavior in mouse models of progranulin-deficient frontotemporal dementia. Proc Natl Acad Sci U S A. 2017;114(19):5029–5034. doi:10.1073/pnas.1700477114
  • Zhang J, Velmeshev D, Hashimoto K, et al. Neurotoxic microglia promote TDP-43 proteinopathy in progranulin deficiency. Nature. 2020:1–5. doi:10.1038/s41586-020-2709-7.
  • Simons C, Dyment D, Bent SJ, et al. A recurrent de novo mutation in TMEM106B causes hypomyelinating leukodystrophy. Brain J Neurol. 2017;140(12):3105–3111. doi:10.1093/brain/awx314
  • Cesani M, Lorioli L, Grossi S, et al. Mutation update of ARSA and PSAP genes causing metachromatic leukodystrophy. Hum Mutat. 2016;37(1):16–27. doi:10.1002/humu.22919
  • Cruts M, Gijselinck I, van der Zee J, et al. Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature. 2006;442(7105):920–924. doi:10.1038/nature05017
  • Baker M, Mackenzie IR, Pickering-Brown SM, et al. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature. 2006;442(7105):916–919. doi:10.1038/nature05016
  • Caroppo P, Le Ber I, Camuzat A, et al. Extensive white matter involvement in patients with frontotemporal lobar degeneration: think progranulin. JAMA Neurol. 2014;71(12):1562–1566. doi:10.1001/jamaneurol.2014.1316
  • Sudre CH, Bocchetta M, Heller C, et al. White matter hyperintensities in progranulin-associated frontotemporal dementia: a longitudinal GENFI study. NeuroImage Clin. 2019;24:102077. doi:10.1016/j.nicl.2019.102077
  • Premi E, Formenti A, Gazzina S, et al. Effect of TMEM106B polymorphism on functional network connectivity in asymptomatic GRN mutation carriers. JAMA Neurol. 2014;71(2):216–221. doi:10.1001/jamaneurol.2013.4835
  • Philtjens S, Van Mossevelde S, van der Zee J, et al. Rare nonsynonymous variants in SORT1 are associated with increased risk for frontotemporal dementia. Neurobiol Aging. 2018;66:181.e3–181.e10. doi:10.1016/j.neurobiolaging.2018.02.011
  • Paloneva J, Kestilä M, Wu J, et al. Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts. Nat Genet. 2000;25(3):357–361. doi:10.1038/77153
  • Paloneva J, Manninen T, Christman G, et al. Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype. Am J Hum Genet. 2002;71(3):656–662. doi:10.1086/342259
  • Ulland TK, Colonna M. TREM2 - a key player in microglial biology and Alzheimer disease. Nat Rev Neurol. 2018;12:1. doi:10.1038/s41582-018-0072-1
  • Paloneva J, Autti T, Raininko R, et al. CNS manifestations of Nasu-Hakola disease: a frontal dementia with bone cysts. Neurology. 2001;56(11):1552–1558. doi:10.1212/WNL.56.11.1552
  • Klünemann HH, Ridha BH, Magy L, et al. The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2. Neurology. 2005;64(9):1502–1507. doi:10.1212/01.WNL.0000160304.00003.CA
  • Chouery E, Delague V, Bergougnoux A, Koussa S, Serre J-L, Mégarbané A. Mutations in TREM2 lead to pure early-onset dementia without bone cysts. Hum Mutat. 2008;29(9):E194–E204. doi:10.1002/humu.20836
  • Guerreiro RJ, Lohmann E, Brás JM, et al. Using exome sequencing to reveal mutations in TREM2 presenting as a frontotemporal dementia-like syndrome without bone involvement. JAMA Neurol. 2013;70(1):78–84. doi:10.1001/jamaneurol.2013.579
  • Guerreiro R, Bilgic B, Guven G, et al. Novel compound heterozygous mutation in TREM2 found in a Turkish frontotemporal dementia-like family. Neurobiol Aging. 2013;34(12):2890.e1–e5. doi:10.1016/j.neurobiolaging.2013.06.005
  • Borroni B, Ferrari F, Galimberti D, et al. Heterozygous TREM2 mutations in frontotemporal dementia. Neurobiol Aging. 2013. doi:10.1016/j.neurobiolaging.2013.09.017
  • Su W-H, Shi Z-H, Liu S-L, Wang X-D, Liu S, Ji Y. The rs75932628 and rs2234253 polymorphisms of the TREM2 gene were associated with susceptibility to frontotemporal lobar degeneration in Caucasian populations. Ann Hum Genet. 2018;82(4):177–185. doi:10.1111/ahg.12241
  • Jonsson T, Stefansson H, Steinberg S, et al. Variant of TREM2 associated with the risk of Alzheimer’s disease. N Engl J Med. 2013;368(2):107–116. doi:10.1056/NEJMoa1211103
  • Guerreiro R, Wojtas A, Bras J, et al. TREM2 variants in Alzheimer’s disease. N Engl J Med. 2013;368(2):117–127. doi:10.1056/NEJMoa1211851
  • Colonna M, Wang Y. TREM2 variants: new keys to decipher Alzheimer disease pathogenesis. Nat Rev Neurosci. 2016;17(4):201–207. doi:10.1038/nrn.2016.7
  • Ulrich JD, Ulland TK, Colonna M, Holtzman DM. Elucidating the Role of TREM2 in Alzheimer’s Disease. Neuron. 2017;94(2):237–248. doi:10.1016/j.neuron.2017.02.042
  • Yeh FL, Hansen DV, Sheng M. TREM2, microglia, and neurodegenerative diseases. Trends Mol Med. 2017;23(6):512–533. doi:10.1016/j.molmed.2017.03.008
  • Cantoni C, Bollman B, Licastro D, et al. TREM2 regulates microglial cell activation in response to demyelination in vivo. Acta Neuropathol (Berl). 2015;129(3):429–447. doi:10.1007/s00401-015-1388-1
  • Poliani PL, Wang Y, Fontana E, et al. TREM2 sustains microglial expansion during aging and response to demyelination. J Clin Invest. 2015;125(5):2161–2170. doi:10.1172/JCI77983
  • Nugent AA, Lin K, van Lengerich B, et al. TREM2 regulates microglial cholesterol metabolism upon chronic phagocytic challenge. Neuron. 2019. doi:10.1016/j.neuron.2019.12.007
  • Cignarella F, Filipello F, Bollman B, et al. TREM2 activation on microglia promotes myelin debris clearance and remyelination in a model of multiple sclerosis. Acta Neuropathol (Berl). 2020;290(686–698):26043. doi:10.1007/s00401-020-02193-z
  • Wider C, Van Gerpen JA, DeArmond S, Shuster EA, Dickson DW, Wszolek ZK. Leukoencephalopathy with spheroids (HDLS) and pigmentary leukodystrophy (POLD): a single entity? Neurology. 2009;72(22):1953–1959. doi:10.1212/WNL.0b013e3181a826c0
  • Rademakers R, Baker M, Nicholson AM, et al. Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids. Nat Genet. 2011;44(2):200–205. doi:10.1038/ng.1027
  • Nicholson AM, Baker MC, Finch NA, et al. CSF1R mutations link POLD and HDLS as a single disease entity. Neurology. 2013;80(11):1033–1040. doi:10.1212/WNL.0b013e31828726a7
  • Adams SJ, Kirk A, Auer RN. Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP): integrating the literature on hereditary diffuse leukoencephalopathy with spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD). J Clin Neurosci. 2018;48:42–49. doi:10.1016/j.jocn.2017.10.060
  • Ginhoux F, Greter M, Leboeuf M, et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science. 2010;330(6005):841–845. doi:10.1126/science.1194637
  • Wang Y, Szretter KJ, Vermi W, et al. IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia. Nat Immunol. 2012;13(8):753–760. doi:10.1038/ni.2360
  • Konno T, Kasanuki K, Ikeuchi T, Dickson DW, Wszolek ZK. CSF1R-related leukoencephalopathy: a major player in primary microgliopathies. Neurology. 2018;91(24):1092–1104. doi:10.1212/WNL.0000000000006642
  • Gelfand JM, Greenfield AL, Barkovich M, et al. Allogeneic HSCT for adult-onset leukoencephalopathy with spheroids and pigmented glia. Brain J Neurol. 2020;143(2):503–511. doi:10.1093/brain/awz390
  • Oosterhof N, Chang IJ, Karimiani EG, et al. Homozygous mutations in CSF1R cause a pediatric-onset leukoencephalopathy and can result in congenital absence of microglia. Am J Hum Genet. 2019;104(5):936–947. doi:10.1016/j.ajhg.2019.03.010
  • Greter M, Lelios I, Pelczar P, et al. Stroma-derived interleukin-34 controls the development and maintenance of langerhans cells and the maintenance of microglia. Immunity. 2012;37(6):1050–1060. doi:10.1016/j.immuni.2012.11.001
  • Wu S, Xue R, Hassan S, et al. Il34-Csf1r pathway regulates the migration and colonization of microglial precursors. Dev Cell. 2018;46(5):552–563.e4. doi:10.1016/j.devcel.2018.08.005
  • Dallabona C, Diodato D, Kevelam SH, et al. Novel (ovario) leukodystrophy related to AARS2 mutations. Neurology. 2014;82(23):2063–2071. doi:10.1212/WNL.0000000000000497
  • Lynch DS, Zhang WJ, Lakshmanan R, et al. Analysis of mutations in AARS2 in a series of CSF1R-negative patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia. JAMA Neurol. 2016;73(12):1433–1439. doi:10.1001/jamaneurol.2016.2229
  • Taglia I, Di Donato I, Bianchi S, et al. AARS2-related ovarioleukodystrophy: clinical and neuroimaging features of three new cases. Acta Neurol Scand. 2018;42(Suppl3):S27. doi:10.1111/ane.12954
  • Goldmann T, Zeller N, Raasch J, et al. USP18 lack in microglia causes destructive interferonopathy of the mouse brain. EMBO J. 2015;34(12):1612–1629. doi:10.15252/embj.201490791
  • Meuwissen MEC, Schot R, Buta S, et al. Human USP18 deficiency underlies type 1 interferonopathy leading to severe pseudo-TORCH syndrome. J Exp Med. 2016;213(7):1163–1174. doi:10.1084/jem.20151529
  • Schwabenland M, Mossad O, Peres AG, et al. Loss of USP18 in microglia induces white matter pathology. Acta Neuropathol Commun. 2019;7(1):106. doi:10.1186/s40478-019-0757-8
  • Honke N, Shaabani N, Zhang D-E, Hardt C, Lang KS. Multiple functions of USP18. Cell Death Dis. 2016;7(11):e2444. doi:10.1038/cddis.2016.326
  • Takata K, Ginhoux F. Poised for action: USP18 restrains microglial activation in the white matter. EMBO J. 2015;34(12):1603–1605. doi:10.15252/embj.201591899
  • Engelen M, Kemp S, Poll-The B-T. X-linked adrenoleukodystrophy: pathogenesis and treatment. Curr Neurol Neurosci Rep. 2014;14(10):486. doi:10.1007/s11910-014-0486-0
  • Huffnagel IC, Laheji FK, Aziz-Bose R, et al. The natural history of adrenal insufficiency in X-linked adrenoleukodystrophy: an International Collaboration. J Clin Endocrinol Metab. 2019;104(1):118–126. doi:10.1210/jc.2018-01307
  • Gong Y, Sasidharan N, Laheji F, et al. Microglial dysfunction as a key pathological change in adrenomyeloneuropathy. Ann Neurol. 2017;82(5):813–827. doi:10.1002/ana.25085
  • Bergner CG, van der Meer F, Winkler A, et al. Microglia damage precedes major myelin breakdown in X-linked adrenoleukodystrophy and metachromatic leukodystrophy. Glia. 2019;67(6):1196–1209. doi:10.1002/glia.23598
  • Eichler FS, Ren J-Q, Cossoy M, et al. Is microglial apoptosis an early pathogenic change in cerebral X-linked adrenoleukodystrophy? Ann Neurol. 2008;63(6):729–742. doi:10.1002/ana.21391
  • Shapiro E, Krivit W, Lockman L, et al. Long-term effect of bone-marrow transplantation for childhood-onset cerebral X-linked adrenoleukodystrophy. Lancet Lond Engl. 2000;356(9231):713–718. doi:10.1016/S0140-6736(00)02629-5
  • Eichler F, Duncan C, Musolino PL, et al. Hematopoietic Stem-cell gene therapy for cerebral adrenoleukodystrophy. N Engl J Med. 2017;377(17):1630–1638. doi:10.1056/NEJMoa1700554
  • Maegawa GHB. Lysosomal leukodystrophies lysosomal storage diseases associated with white matter abnormalities. J Child Neurol. 2019;34(6):339–358. doi:10.1177/0883073819828587
  • Suzuki K. Twenty five years of the “psychosine hypothesis”: a personal perspective of its history and present status. Neurochem Res. 1998;23(3):251–259. doi:10.1023/a:1022436928925
  • Graziano ACE, Cardile V. History, genetic, and recent advances on Krabbe disease. Gene. 2015;555(1):2–13. doi:10.1016/j.gene.2014.09.046
  • Nicaise AM, Bongarzone ER, Crocker SJ. A microglial hypothesis of globoid cell leukodystrophy pathology. J Neurosci Res. 2016;94(11):1049–1061. doi:10.1002/jnr.23773
  • Ijichi K, Brown GD, Moore CS, et al. MMP-3 mediates psychosine-induced globoid cell formation: implications for leukodystrophy pathology. Glia. 2013;61(5):765–777. doi:10.1002/glia.22471
  • Potter GB, Santos M, Davisson MT, et al. Missense mutation in mouse GALC mimics human gene defect and offers new insights into Krabbe disease. Hum Mol Genet. 2013;22(17):3397–3414. doi:10.1093/hmg/ddt190
  • Giri S, Khan M, Rattan R, Singh I, Singh AK. Krabbe disease: psychosine-mediated activation of phospholipase A2 in oligodendrocyte cell death. J Lipid Res. 2006;47(7):1478–1492. doi:10.1194/jlr.M600084-JLR200
  • Ida H, Rennert OM, Watabe K, Eto Y, Maekawa K. Pathological and biochemical studies of fetal Krabbe disease. Brain Dev. 1994;16(6):480–484. doi:10.1016/0387-7604(94)90013-2
  • Krivit W, Shapiro EG, Peters C, et al. Hematopoietic stem-cell transplantation in globoid-cell leukodystrophy. N Engl J Med. 1998;338(16):1119–1126. doi:10.1056/NEJM199804163381605
  • Escolar ML, Poe MD, Provenzale JM, et al. Transplantation of umbilical-cord blood in babies with infantile Krabbe’s disease. N Engl J Med. 2005;352(20):2069–2081. doi:10.1056/NEJMoa042604
  • McGraw P, Liang L, Escolar M, Mukundan S, Kurtzberg J, Provenzale JM. Krabbe disease treated with hematopoietic stem cell transplantation: serial assessment of anisotropy measurements–initial experience. Radiology. 2005;236(1):221–230. doi:10.1148/radiol.2353040716
  • Giera S, Luo R, Ying Y, et al. Microglial transglutaminase-2 drives myelination and myelin repair via GPR56/ADGRG1 in oligodendrocyte precursor cells. eLife. 2018;7. doi:10.7554/eLife.33385
  • Wang J, He X, Meng H, et al. Robust myelination of regenerated axons induced by combined manipulations of GPR17 and microglia. Neuron. 2020;108(5):876–886.e4. doi:10.1016/j.neuron.2020.09.016
  • Lund H, Pieber M, Parsa R, et al. Fatal demyelinating disease is induced by monocyte-derived macrophages in the absence of TGF-β signaling. Nat Immunol. 2018;19(5):1–7. doi:10.1038/s41590-018-0091-5
  • Qin Y, Garrison BS, Ma W, et al. A milieu molecule for TGF-β required for microglia function in the nervous system. Cell. 2018;174(1):156–171.e16. doi:10.1016/j.cell.2018.05.027
  • Arnold TD, Lizama CO, Cautivo KM, et al. Impaired αVβ8 and TGFβ signaling lead to microglial dysmaturation and neuromotor dysfunction. J Exp Med. 2019;216(4):900–915. doi:10.1084/jem.20181290
  • Li Q, Cheng Z, Zhou L, et al. Developmental heterogeneity of microglia and brain myeloid cells revealed by deep single-cell RNA sequencing. Neuron. 2019;101(2):207–223.e10. doi:10.1016/j.neuron.2018.12.006
  • Safaiyan S, Besson-Girard S, Kaya T, et al. White matter aging drives microglial diversity. Neuron. 2021. doi:10.1016/j.neuron.2021.01.027
  • Sirkis DW, Geier EG, Bonham LW, Karch CM, Yokoyama JS. Recent advances in the genetics of frontotemporal dementia. Curr Genet Med Rep. 2019;7(1):41–52. doi:10.1007/s40142-019-0160-6
  • Mahoney CJ, Simpson IJA, Nicholas JM, et al. Longitudinal diffusion tensor imaging in frontotemporal dementia. Ann Neurol. 2015;77(1):33–46. doi:10.1002/ana.24296
  • Jiskoot LC, Bocchetta M, Nicholas JM, et al. Presymptomatic white matter integrity loss in familial frontotemporal dementia in the GENFI cohort: a cross-sectional diffusion tensor imaging study. Ann Clin Transl Neurol. 2018;5(9):1025–1036. doi:10.1002/acn3.601
  • Le Ber I, Camuzat A, Hannequin D, et al. Phenotype variability in progranulin mutation carriers: a clinical, neuropsychological, imaging and genetic study. Brain J Neurol. 2008;131(Pt 3):732–746. doi:10.1093/brain/awn012
  • Ameur F, Colliot O, Caroppo P, et al. White matter lesions in FTLD: distinct phenotypes characterize GRN and C9ORF72 mutations. Neurol Genet. 2016;2(1):e47. doi:10.1212/NXG.0000000000000047
  • Woollacott IOC, Bocchetta M, Sudre CH, et al. Pathological correlates of white matter hyperintensities in a case of progranulin mutation associated frontotemporal dementia. Neurocase. 2018;24(3):166–174. doi:10.1080/13554794.2018.1506039
  • Zhou X, Sun L, Bracko O, et al. Impaired prosaposin lysosomal trafficking in frontotemporal lobar degeneration due to progranulin mutations. Nat Commun. 2017;8(1):1–14. doi:10.1038/ncomms15277
  • Götzl JK, Brendel M, Werner G, et al. Opposite microglial activation stages upon loss of PGRN or TREM2 result in reduced cerebral glucose metabolism. EMBO Mol Med. 2019;11(6). doi:10.15252/emmm.201809711
  • Cruchaga C, Graff C, Chiang -H-H, et al. Association of TMEM106B gene polymorphism with age at onset in granulin mutation carriers and plasma granulin protein levels. Arch Neurol. 2011;68(5):581–586. doi:10.1001/archneurol.2010.350
  • Finch N, Carrasquillo MM, Baker M, et al. TMEM106B regulates progranulin levels and the penetrance of FTLD in GRN mutation carriers. Neurology. 2011;76(5):467–474. doi:10.1212/WNL.0b013e31820a0e3b
  • van der Zee J, Van Langenhove T, Kleinberger G, et al. TMEM106B is associated with frontotemporal lobar degeneration in a clinically diagnosed patient cohort. Brain J Neurol. 2011;134(Pt3):808–815. doi:10.1093/brain/awr007
  • Dopper EGP, Rombouts SARB, Jiskoot LC, et al. Structural and functional brain connectivity in presymptomatic familial frontotemporal dementia. Neurology. 2014;83(2):e19–e26. doi:10.1212/WNL.0000000000000583
  • Feng T, Mai S, Roscoe JM, et al. Loss of TMEM106B and PGRN leads to severe lysosomal abnormalities and neurodegeneration in mice. EMBO Rep. 2020;127(10):e50219. doi:10.15252/embr.202050219
  • Werner G, Damme M, Schludi M, et al. Loss of TMEM106B potentiates lysosomal and FTLD-like pathology in progranulin-deficient mice. EMBO Rep. 2020;21(10):e50241. doi:10.15252/embr.202050241
  • Zhou X, Brooks M, Jiang P, et al. Loss of Tmem106b exacerbates FTLD pathologies and causes motor deficits in progranulin-deficient mice. EMBO Rep. 2020;39:e50197. doi:10.15252/embr.202050197
  • Clayton EL, Isaacs AM. Progranulin and TMEM106B: when two become wan. EMBO Rep. 2020;21(10):e51668. doi:10.15252/embr.202051668
  • Zhou X, Nicholson AM, Ren Y, et al. Loss of TMEM106B leads to myelination deficits: implications for frontotemporal dementia treatment strategies. Brain J Neurol. 2020;61(6):435–1919. doi:10.1093/brain/awaa141
  • Feng T, Sheng RR, Solé-Domènech S, et al. A role of the frontotemporal lobar degeneration risk factor TMEM106B in myelination. Brain J Neurol. 2020;143(7):2255–2271. doi:10.1093/brain/awaa154
  • Zhou X, Rademakers R. TMEM106B and myelination: rare leukodystrophy families reveal unexpected connections. Brain J Neurol. 2017;140(12):3069–3080. doi:10.1093/brain/awx318
  • Yan H, Kubisiak T, Ji H, Xiao J, Wang J, Burmeister M. The recurrent mutation in TMEM106B also causes hypomyelinating leukodystrophy in China and is a CpG hotspot. Brain J Neurol. 2018;141(5):e36. doi:10.1093/brain/awy029
  • Panman JL, Jiskoot LC, Bouts MJRJ, et al. Gray and white matter changes in presymptomatic genetic frontotemporal dementia: a longitudinal MRI study. Neurobiol Aging. 2019;76:115–124. doi:10.1016/j.neurobiolaging.2018.12.017
  • Amick J, Ferguson SM. C9orf72: at the intersection of lysosome cell biology and neurodegenerative disease. Traffic Cph Den. 2017;18(5):267–276. doi:10.1111/tra.12477
  • van Blitterswijk M, Mullen B, Nicholson AM, et al. TMEM106B protects C9ORF72 expansion carriers against frontotemporal dementia. Acta Neuropathol (Berl). 2014;127(3):397–406. doi:10.1007/s00401-013-1240-4
  • Gallagher MD, Suh E, Grossman M, et al. TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions. Acta Neuropathol (Berl). 2014;127(3):407–418. doi:10.1007/s00401-013-1239-x
  • Premi E, Grassi M, van Swieten J, et al. Cognitive reserve and TMEM106B genotype modulate brain damage in presymptomatic frontotemporal dementia: a GENFI study. Brain J Neurol. 2017;140(6):1784–1791. doi:10.1093/brain/awx103
  • Spiegel R, Bach G, Sury V, et al. A mutation in the saposin A coding region of the prosaposin gene in an infant presenting as Krabbe disease: first report of saposin A deficiency in humans. Mol Genet Metab. 2005;84(2):160–166. doi:10.1016/j.ymgme.2004.10.004
  • Vaccaro AM, Motta M, Tatti M, et al. Saposin C mutations in Gaucher disease patients resulting in lysosomal lipid accumulation, saposin C deficiency, but normal prosaposin processing and sorting. Hum Mol Genet. 2010;19(15):2987–2997. doi:10.1093/hmg/ddq204
  • Motta M, Tatti M, Furlan F, et al. Clinical, biochemical and molecular characterization of prosaposin deficiency. Clin Genet. 2016;90(3):220–229. doi:10.1111/cge.12753
  • Kolter T, Sandhoff K. Principles of lysosomal membrane digestion: stimulation of sphingolipid degradation by sphingolipid activator proteins and anionic lysosomal lipids. Annu Rev Cell Dev Biol. 2005;21(1):81–103. doi:10.1146/annurev.cellbio.21.122303.120013
  • Zhou X, Sun L, Bastos de Oliveira F, et al. Prosaposin facilitates sortilin-independent lysosomal trafficking of progranulin. J Cell Biol. 2015;210(6):991–1002. doi:10.1083/jcb.201502029
  • Arrant AE, Roth JR, Boyle NR, et al. Impaired β-glucocerebrosidase activity and processing in frontotemporal dementia due to progranulin mutations. Acta Neuropathol Commun. 2019;7(1):1–17. doi:10.1186/s40478-019-0872-6
  • Valdez C, Ysselstein D, Young TJ, Zheng J, Krainc D. Progranulin mutations result in impaired processing of prosaposin and reduced glucocerebrosidase activity. Hum Mol Genet. 2020;29(5):716–726. doi:10.1093/hmg/ddz229
  • Nicholson AM, Finch NA, Almeida M, et al. Prosaposin is a regulator of progranulin levels and oligomerization. Nat Commun. 2016;7(1):11992. doi:10.1038/ncomms11992
  • Hu F, Padukkavidana T, Vægter CB, et al. Sortilin-mediated endocytosis determines levels of the frontotemporal dementia protein, progranulin. Neuron. 2010;68(4):654–667. doi:10.1016/j.neuron.2010.09.034
  • Wang Y, Cella M, Mallinson K, et al. TREM2 lipid sensing sustains the microglial response in an Alzheimer’s Disease Model. Cell. 2015;160(6):1061–1071. doi:10.1016/j.cell.2015.01.049
  • Oosterhof N, Kuil LE, van der Linde HC, et al. Colony-stimulating factor 1 receptor (CSF1R) regulates microglia density and distribution, but not microglia differentiation in vivo. Cell Rep. 2018;24(5):1203–1217.e6. doi:10.1016/j.celrep.2018.06.113
  • Kempthorne L, Yoon H, Madore C, et al. Loss of homeostatic microglial phenotype in CSF1R-related Leukoencephalopathy. Acta Neuropathol Commun. 2020;8(1):1–15. doi:10.1186/s40478-020-00947-0
  • Prokop S, Miller KR, Drost N, et al. Impact of peripheral myeloid cells on amyloid-β pathology in Alzheimer’s disease-like mice. J Exp Med. 2015;212(11):1811–1818. doi:10.1084/jem.20150479