{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:14:41Z","timestamp":1790622881856,"version":"4.1.0"},"reference-count":205,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T00:00:00Z","timestamp":1654473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cLa Caixa\u201d Foundation","award":["100010434"],"award-info":[{"award-number":["100010434"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Primary microglial leukodystrophy or leukoencephalopathy are disorders in which a genetic defect linked to microglia causes cerebral white matter damage. Pigmented orthochromatic leukodystrophy, adult-onset orthochromatic leukodystrophy associated with pigmented macrophages, hereditary diffuse leukoencephalopathy with (axonal) spheroids, and adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) are different terms apparently used to designate the same disease. However, ALSP linked to dominantly inherited mutations in CSF1R (colony stimulating factor receptor 1) cause CSF-1R-related leukoencephalopathy (CRP). Yet, recessive ALSP with ovarian failure linked to AARS2 (alanyl-transfer (t)RNA synthase 2) mutations (LKENP) is a mitochondrial disease and not a primary microglial leukoencephalopathy. Polycystic membranous lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL; Nasu\u2013Hakola disease: NHD) is a systemic disease affecting bones, cerebral white matter, selected grey nuclei, and adipose tissue The disease is caused by mutations of one of the two genes TYROBP or TREM2, identified as PLOSL1 and PLOSL2, respectively. TYROBP associates with receptors expressed in NK cells, B and T lymphocytes, dendritic cells, monocytes, macrophages, and microglia. TREM2 encodes the protein TREM2 (triggering receptor expressed on myeloid cells 2), which forms a receptor signalling complex with TYROBP in macrophages and dendritic cells. Rather than pure microglial leukoencephalopathy, NHD can be considered a multisystemic \u201cimmunological\u201d disease.<\/jats:p>","DOI":"10.3390\/ijms23116341","type":"journal-article","created":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T10:08:24Z","timestamp":1654510104000},"page":"6341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["The Primary Microglial Leukodystrophies: A Review"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9888-8754","authenticated-orcid":false,"given":"Isidro","family":"Ferrer","sequence":"first","affiliation":[{"name":"Network Centre of Biomedical Research of Neurodegenerative Diseases (CIBERNED), Department of Pathology and Experimental Therapeutics, Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, 08907 Barcelona, L\u2019Hospitalet de Llobregat, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s00401-017-1739-1","article-title":"Leukodystrophies: A proposed classification system based on pathological changes and pathogenetic mechanisms","volume":"134","author":"Bugiani","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/nrneurol.2017.175","article-title":"Adulthood leukodystrophies","volume":"14","author":"Curiel","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1093\/brain\/awx045","article-title":"Clinical and genetic characterization of leukoencephalopathies in adults","volume":"140","author":"Lynch","year":"2017","journal-title":"Brain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/S1474-4422(19)30143-7","article-title":"Diagnosis, prognosis, and treatment of leukodystrophies","volume":"18","author":"Schiffmann","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1148\/rg.2019180081","article-title":"Adult Leukodystrophies: A Step-by-Step Diagnostic Approach","volume":"39","author":"Resende","year":"2019","journal-title":"RadioGraphics"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105087","DOI":"10.1016\/j.nbd.2020.105087","article-title":"Glial cells in the driver seat of leukodystrophy pathogenesis","volume":"146","author":"Garcia","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nrneurol.2010.17-c1","article-title":"Nasu\u2013Hakola disease and primary microglial dysfunction","volume":"6","author":"Bianchin","year":"2010","journal-title":"Nat. Rev. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1212\/WNL.0000000000006642","article-title":"CSF1R-related leukoencephalopathy. A major player in primary microgliopathies","volume":"91","author":"Konno","year":"2018","journal-title":"Neurology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"dmm048925","DOI":"10.1242\/dmm.048925","article-title":"The multicellular interplay of microglia in health and disease: Lessons from leukodystrophy","volume":"14","author":"Berdowski","year":"2021","journal-title":"Dis. Model. Mech."},{"key":"ref_10","first-page":"254","article-title":"Ludo van Bogaert (1897\u20131989)","volume":"96","author":"Martin","year":"1996","journal-title":"Acta Neurol. Belg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1097\/00005072-198709000-00007","article-title":"Pigmentary Type of Orthochromatic Leukodystrophy: A new case with ultrastructural and biochemical study","volume":"46","author":"Gray","year":"1987","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_12","first-page":"337","article-title":"Leucodystrophy with pigmented glial and scavenger cells (pigmentary type of orthochromatic leucodystrophy)","volume":"14","author":"Ferrer","year":"1988","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/BF00293382","article-title":"The dominant form of the pigmentary orthochromatic leukodystrophy","volume":"82","author":"Constantinidis","year":"1991","journal-title":"Acta Neuropathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1017\/S0317167100021491","article-title":"A Rare Form of Adult Onset Leukodystrophy: Orthochromatic Leukodystrophy with Pigmented Glia","volume":"24","author":"Shannon","year":"1997","journal-title":"Can. J. Neurol. Sci. J. Can. Sci. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/ane.12954","article-title":"AARS2-related ovarioleukodystrophy: Clinical and neuroimaging features of three new cases","volume":"138","author":"Taglia","year":"2018","journal-title":"Acta Neurol. Scand."},{"key":"ref_16","first-page":"1","article-title":"Hereditary diffuse leucoencephalopathy with spheroids","volume":"314","author":"Axelsson","year":"1984","journal-title":"Acta Psychiatr. Scand. Suppl."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1007\/s00401-006-0046-z","article-title":"Hereditary diffuse leukoencephalopathy with spheroids: Clinical, pathologic and genetic studies of a new kindred","volume":"111","author":"Baba","year":"2006","journal-title":"Acta Neuropathol."},{"key":"ref_18","first-page":"665","article-title":"Hereditary diffuse leukoencephalopathy with spheroids: Ultrastructural and immunoe-lectron microscopic studies","volume":"3","author":"Lin","year":"2010","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1097\/NEN.0000000000000139","article-title":"Early Pathologic Changes in Hereditary Diffuse Leukoencephalopathy with Spheroids","volume":"73","author":"Riku","year":"2014","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1111\/bpa.12120","article-title":"Enlarging the Nosological Spectrum of Hereditary Diffuse Leukoencephalopathy with Axonal Spheroids (HDLS)","volume":"24","author":"Hoffmann","year":"2014","journal-title":"Brain Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1212\/WNL.0b013e3181a826c0","article-title":"Leukoencephalopathy with spheroids (HDLS) and pigmentary leukodystrophy (POLD): A single entity?","volume":"72","author":"Wider","year":"2009","journal-title":"Neurology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1212\/WNL.54.2.463","article-title":"Autosomal dominant diffuse leukoencephalopathy with neuroaxonal spheroids","volume":"54","author":"Naidu","year":"2000","journal-title":"Neurology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/s00401-004-0847-x","article-title":"Adult onset leukodystrophy with neuroaxonal spheroids and pigmented glia: Report of a family, historical perspective, and review of the literature","volume":"107","author":"Marotti","year":"2004","journal-title":"Acta Neuropathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s00401-005-1113-6","article-title":"Autosomal dominant leukodystrophy with axonal spheroids and pigmented glia: Clinical and neuropathological characteristics","volume":"111","author":"Itoh","year":"2005","journal-title":"Acta Neuropathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1097\/nen.0b013e3180986247","article-title":"A Comparative Morphologic Analysis of Adult Onset Leukodystrophy with Neuroaxonal Spheroids and Pigmented Glia-A Role for Oxidative Damage","volume":"66","author":"Ali","year":"2007","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/j.1750-3639.2008.00163.x","article-title":"Adult Onset Leukodystrophy with Neuroaxonal Spheroids: Clinical, Neuroimaging and Neuropathologic Observations","volume":"19","author":"Freeman","year":"2008","journal-title":"Brain Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1136\/jnnp-2015-310788","article-title":"Hereditary leukoencephalopathy with axonal spheroids: A spectrum of phenotypes from CNS vasculitis to parkinsonism in an adult onset leukodystrophy series","volume":"87","author":"Lynch","year":"2015","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jns.2011.10.006","article-title":"Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS): A misdiagnosed disease entity","volume":"314","author":"Sundal","year":"2012","journal-title":"J. Neurol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1212\/WNL.0b013e31828726a7","article-title":"CSF1R mutations link POLD and HDLS as a single disease entity","volume":"80","author":"Nicholson","year":"2013","journal-title":"Neurology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1212\/WNL.0000000000000026","article-title":"Hereditary diffuse leukoencephalopathy with axonal spheroids: More than just a rare disease","volume":"82","author":"Wider","year":"2013","journal-title":"Neurology"},{"key":"ref_31","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Stephens, K., and Amemiya, A. (2017). CSFR1-related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia. GeneReviews\u00ae [Internet], University of Washington."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/ng.1027","article-title":"Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids","volume":"44","author":"Rademakers","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1212\/WNL.0000000000000497","article-title":"Novel (ovario) leukodystrophy related to AARS2 mutations","volume":"82","author":"Dallabona","year":"2014","journal-title":"Neurology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.ajhg.2015.02.012","article-title":"Loss-of-Function Alanyl-tRNA Synthetase Mutations Cause an Autosomal-Recessive Early-Onset Epileptic Encephalopathy with Persistent Myelination Defect","volume":"96","author":"Simons","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2352","DOI":"10.1038\/s41436-021-01286-8","article-title":"Expanded phenotype of AARS1-related white matter disease","volume":"23","author":"Helman","year":"2021","journal-title":"Genet. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/ene.13125","article-title":"Clinical and genetic characterization of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia associated with CSF1R mutation","volume":"24","author":"Konno","year":"2016","journal-title":"Eur. J. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.parkreldis.2013.05.013","article-title":"Parkinsonian features in hereditary diffuse leukoencephalopathy with spheroids (HDLS) and CSF1R mutations","volume":"19","author":"Sundal","year":"2013","journal-title":"Park. Relat. Disord."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1007\/s00415-012-6680-6","article-title":"Adult-onset leukoencephalopathy with neuroaxonal spheroids and pigmented glia: Report of five cases and a new mutation","volume":"260","author":"Kleinfeld","year":"2012","journal-title":"J. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1111\/nan.12046","article-title":"A clinicopathological and genetic study of sporadic diffuse leukoencephalopathy with spheroids: A report of two cases","volume":"39","author":"Kimura","year":"2013","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1001\/jamaneurol.2013.698","article-title":"Genetic Analysis of Inherited Leukodystrophies","volume":"70","author":"Guerreiro","year":"2013","journal-title":"JAMA Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1212\/WNL.0000000000000046","article-title":"Haploinsufficiency of CSF-1R and clinicopathologic characterization in patients with HDLS","volume":"82","author":"Konno","year":"2013","journal-title":"Neurology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.jns.2016.06.013","article-title":"A family with hereditary diffuse leukoencephalopathy with spheroids caused by a novel c.2442+2T>C mutation in the CSF1R gene","volume":"367","author":"Kawakami","year":"2016","journal-title":"J. Neurol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"S39","DOI":"10.1016\/j.parkreldis.2017.08.018","article-title":"Cognitive dysfunction and symptoms of movement disorders in adult-onset leukoencephalopathy with axonal spheroids and pigmented glia","volume":"46","author":"Ikeuchi","year":"2018","journal-title":"Park. Relat. Disord."},{"key":"ref_44","first-page":"6093","article-title":"A novel dominant-negative mutation of the CSF1R gene causes adult-onset leukoencephalopathy with axonal spheroids and pigmented glia","volume":"11","author":"Leng","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"492","DOI":"10.5414\/NP300603","article-title":"Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia: Report on a case with morphometric studies","volume":"32","author":"Calatayud","year":"2013","journal-title":"Clin. Neuropathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s40035-019-0171-y","article-title":"Clinicopathologic characterization and abnormal autophagy of CSF1R-related leukoencephalopathy","volume":"8","author":"Tian","year":"2019","journal-title":"Transl. Neurodegener."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1111\/psyg.12387","article-title":"Remarkable behavioural signs and progressive non-fluent aphasia in a patient with adult-onset leucoencephalopathy with axonal spheroids and pigmented glia","volume":"19","author":"Funayama","year":"2018","journal-title":"Psychogeriatrics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"319","DOI":"10.3233\/JAD-150097","article-title":"A Novel CSF1R Mutation in a Patient with Clinical and Neuroradiological Features of Hereditary Diffuse Leukoencephalopathy with Axonal Spheroids","volume":"47","author":"Stabile","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Shu, Y., Long, L., Liao, S., Yang, J., Li, J., Qiu, W., Yang, Y., Bao, J., Wu, A., and Hu, X. (2016). Involvement of the optic nerve in mutated CSF1R-induced hereditary diffuse leukoencephalopathy with axonal spheroids. BMC Neurol., 16.","DOI":"10.1186\/s12883-016-0694-0"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1001\/jamaneurol.2016.2229","article-title":"Analysis of Mutations in AARS2 in a Series of CSF1R-Negative Patients with Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia","volume":"73","author":"Lynch","year":"2016","journal-title":"JAMA Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s10048-019-00579-0","article-title":"A novel CSF-1R mutation in a family with hereditary diffuse leukoencephalopathy with axonal spheroids misdiagnosed as hydrocephalus","volume":"20","author":"Wang","year":"2019","journal-title":"Neurogenetics"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1007\/s10072-019-04116-7","article-title":"Biopsy histopathology in the diagnosis of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP)","volume":"41","author":"Mao","year":"2019","journal-title":"Neurol. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1038\/s10038-018-0446-7","article-title":"An adolescence-onset male leukoencephalopathy with remarkable cerebellar atrophy and novel compound heterozygous AARS2 gene mutations: A case report","volume":"63","author":"Dong","year":"2018","journal-title":"J. Hum. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1212\/01.wnl.0000325916.30701.21","article-title":"Insights into the dynamics of hereditary diffuse leukoencephalopathy with axonal spheroids","volume":"71","author":"Wider","year":"2008","journal-title":"Neurology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1212\/WNL.0b013e318263575a","article-title":"MRI characteristics and scoring in HDLS due to CSF1R gene mutations","volume":"79","author":"Sundal","year":"2012","journal-title":"Neurology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1007\/s00415-013-7093-x","article-title":"An adult-onset leukoencephalopathy with axonal spheroids and pigmented glia accompanied by brain calcifications: A case report and a literature review of brain calcifications disorders","volume":"260","author":"Fujioka","year":"2013","journal-title":"J. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1007\/s00415-014-7509-2","article-title":"Imaging features in conventional MRI, spectroscopy and diffusion weighted images of hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS)","volume":"261","author":"Bender","year":"2014","journal-title":"J. Neurol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s40478-015-0219-x","article-title":"Common neuropathological features underlie distinct clinical presentations in three siblings with hereditary diffuse leukoencephalopathy with spheroids caused by CSF1R p.Arg782His","volume":"3","author":"Robinson","year":"2015","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1001\/jamaneurol.2017.1062","article-title":"Brain Calcifications in Adult-Onset Genetic Leukoencephalopathies","volume":"74","author":"Ayrignac","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.3174\/ajnr.A5744","article-title":"Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia: An MRI Study of 16 French Cases","volume":"39","author":"Codjia","year":"2018","journal-title":"Am. J. Neuroradiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3174\/ajnr.A4938","article-title":"Diagnostic Value of Brain Calcifications in Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia","volume":"38","author":"Konno","year":"2016","journal-title":"Am. J. Neuroradiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"297","DOI":"10.2463\/mrms.mp.2016-0016","article-title":"MR Spectroscopy in Patients with Hereditary Diffuse Leukoencephalopathy with Spheroids and Asymptomatic Carriers of Colony-stimulating Factor 1 Receptor Mutation","volume":"16","author":"Abe","year":"2017","journal-title":"Magn. Reson. Med Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.jns.2010.06.027","article-title":"Adult-onset leukodystrophy with axonal spheroids","volume":"297","author":"Mendes","year":"2010","journal-title":"J. Neurol. Sci."},{"key":"ref_64","first-page":"285","article-title":"Adult onset leukodystrophy with neuroaxonal spheroids and demyelinating plaque-like lesions","volume":"32","author":"Shah","year":"2011","journal-title":"Neuropathology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1097\/NEN.0000000000000008","article-title":"Adult-Onset Leukodystrophy: Review of 3 Clinicopathologic Phenotypes and a Proposed Classification","volume":"72","author":"Alturkustani","year":"2013","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1111\/bpa.12443","article-title":"Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu-Hakola disease: Lesion staging and dynamic changes of axons and microglial subsets","volume":"27","author":"Oyanagi","year":"2017","journal-title":"Brain Pathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1097\/NEN.0000000000000168","article-title":"Pathologic Staging of White Matter Lesions in Adult-Onset Leukoencephalopathy\/Leukodystrophy With Axonal Spheroids","volume":"74","author":"Alturkustani","year":"2015","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1002\/ajmg.b.32100","article-title":"CSF1R mutations identified in three families with autosomal dominantly inherited leukoencephalopathy","volume":"159B","author":"Mitsui","year":"2012","journal-title":"Am. J. Med. Genet. Part B Neuropsychiatr. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.jns.2013.06.007","article-title":"A novel A781V mutation in the CSF1R gene causes hereditary diffuse leucoencephalopathy with axonal spheroids","volume":"332","author":"Ahmed","year":"2013","journal-title":"J. Neurol. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1212\/01.wnl.0000436945.01023.ac","article-title":"De novo mutations in hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS)","volume":"81","author":"Karle","year":"2013","journal-title":"Neurology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1111\/ene.12572","article-title":"Hereditary diffuse leukoencephalopathy with spheroids with phenotype of primary progressive multiple sclerosis","volume":"22","author":"Sundal","year":"2014","journal-title":"Eur. J. Neurol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1007\/s10072-016-2634-6","article-title":"Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS): Update on molecular genetics","volume":"37","author":"Stabile","year":"2016","journal-title":"Neurol. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"491","DOI":"10.3389\/fgene.2019.00491","article-title":"A Novel Splicing Mutation in the CSF1R Gene in a Family with Hereditary Diffuse Leukoencephalopathy with Axonal Spheroids","volume":"10","author":"Yang","year":"2019","journal-title":"Front. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.jns.2014.12.021","article-title":"Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia linked CSF1R mutation: Report of four Korean cases","volume":"349","author":"Kim","year":"2014","journal-title":"J. Neurol. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"10042","DOI":"10.1038\/srep10042","article-title":"Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia Caused by a Novel R782G Mutation in CSF1R","volume":"5","author":"Foulds","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1177\/1971400918822136","article-title":"Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia: Clinical and imaging characteristics","volume":"32","author":"Makary","year":"2019","journal-title":"Neuroradiol. J."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e00595","DOI":"10.1002\/mgg3.595","article-title":"Functional characterization of a novel CSF1R mutation causing hereditary diffuse leukoencephalopathy with spheroids","volume":"7","author":"Kraya","year":"2019","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/ene.14086","article-title":"Factors predictive of the presence of a CSF1R mutation in patients with leukoencephalopathy","volume":"27","author":"Kondo","year":"2019","journal-title":"Eur. J. Neurol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1007\/s00415-018-9017-2","article-title":"Identification and functional characterization of novel mutations including frameshift mutation in exon 4 of CSF1R in patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia","volume":"265","author":"Miura","year":"2018","journal-title":"J. Neurol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Chitu, V., G\u00f6khan, \u015e., and Stanley, E.R. (2021). Modeling CSF-1 receptor deficiency diseases\u2014How close are we?. FEBS J.","DOI":"10.1111\/febs.16085"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/j.ajhg.2019.03.010","article-title":"Homozygous Mutations in CSF1R Cause a Pediatric-Onset Leukoencephalopathy and Can Result in Congenital Absence of Microglia","volume":"104","author":"Oosterhof","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.ajhg.2019.03.004","article-title":"Bi-allelic CSF1R Mutations Cause Skeletal Dysplasia of Dysosteosclerosis-Pyle Disease Spectrum and Degenerative Encephalopathy with Brain Malformation","volume":"104","author":"Guo","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1093\/jnen\/nly087","article-title":"AARS2 Compound Heterozygous Variants in a Case of Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia","volume":"77","author":"Wang","year":"2018","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/jhg.2016.64","article-title":"The first Japanese case of leukodystrophy with ovarian failure arising from novel compound heterozygous AARS2 mutations","volume":"61","author":"Hamatani","year":"2016","journal-title":"J. Hum. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/jhg.2016.126","article-title":"Novel AARS2 gene mutation producing leukodystrophy: A case report","volume":"62","author":"Szpisjak","year":"2016","journal-title":"J. Hum. Genet."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e21","DOI":"10.1111\/ene.13245","article-title":"Two Korean siblings with recently described ovarioleukodystrophy related to AARS2 mutations","volume":"24","author":"Lee","year":"2017","journal-title":"Eur. J. Neurol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1002\/ajmg.a.61188","article-title":"Expansion of the clinical spectrum associated with AARS2-related disorders","volume":"179","author":"Srivastava","year":"2019","journal-title":"Am. J. Med Genet. Part A"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/s40478-019-0843-y","article-title":"An AARS variant as the likely cause of Swedish type hereditary diffuse leukoencephalopathy with spheroids","volume":"7","author":"Sundal","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1080\/13816810.2017.1350723","article-title":"Retinopathy and optic atrophy: Expanding the phenotypic spectrum of pathogenic variants in the AARS2 gene","volume":"39","author":"Peragallo","year":"2017","journal-title":"Ophthalmic Genet."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1007\/s12311-019-01080-y","article-title":"Alanyl-tRNA Synthetase 2 (AARS2)-Related Ataxia Without Leukoencephalopathy","volume":"19","author":"Kuo","year":"2019","journal-title":"Cerebellum"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e00582","DOI":"10.1002\/mgg3.582","article-title":"AARS 2 leukoencephalopathy: A new variant of mitochondrial encephalomyopathy","volume":"7","author":"Tang","year":"2019","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.ajhg.2011.04.006","article-title":"Exome Sequencing Identifies Mitochondrial Alanyl-tRNA Synthetase Mutations in Infantile Mitochondrial Cardiomyopathy","volume":"88","author":"Tyynismaa","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1017\/S1047951116001876","article-title":"Thymidine kinase 2 and alanyl-tRNA synthetase 2 deficiencies cause lethal mitochondrial cardiomyopathy: Case reports and review of the literature","volume":"27","author":"Mazurova","year":"2016","journal-title":"Cardiol. Young"},{"key":"ref_94","first-page":"258","article-title":"Instability of the mitochondrial alanyl-tRNA synthetase underlies fatal infantile-onset cardiomyopathy","volume":"28","author":"Sommerville","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s13258-020-00933-9","article-title":"Alanyl-tRNA synthetase 1 (AARS1) gene mutation in a family with intermediate Charcot-Marie-Tooth neuropathy","volume":"42","author":"Lee","year":"2020","journal-title":"Genes Genom."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"100681","DOI":"10.1016\/j.ymgmr.2020.100681","article-title":"Recurrent acute liver failure in alanyl-tRNA synthe-tase-1 (AARS1) deficiency","volume":"25","author":"Marten","year":"2020","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.tcb.2004.09.016","article-title":"CSF-1 regulation of the wandering macrophage: Complexity in action","volume":"14","author":"Pixley","year":"2004","journal-title":"Trends Cell Biol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Erblich, B., Zhu, L., Etgen, A.M., Dobrenis, K., and Pollard, J.W. (2011). Absence of Colony Stimulation Factor-1 Receptor Results in Loss of Microglia, Disrupted Brain Development and Olfactory Deficits. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026317"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.nbd.2014.12.001","article-title":"Phenotypic characterization of a Csf1r haploinsufficient mouse model of adult-onset leukodystrophy with axonal spheroids and pigmented glia (ALSP)","volume":"74","author":"Chitu","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"104867","DOI":"10.1016\/j.nbd.2020.104867","article-title":"Altered features of monocytes in adult onset leukoencephalopathy with axonal spheroids and pigmented glia: A clue to the pathomechanism of microglial dyshomeostasis","volume":"140","author":"Hamatani","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1016\/j.celrep.2018.06.113","article-title":"Colony-Stimulating Factor 1 Receptor (CSF1R) Regulates Microglia Density and Distribution, but Not Microglia Differentiation In Vivo","volume":"24","author":"Oosterhof","year":"2018","journal-title":"Cell Rep."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/nrneurol.2010.17","article-title":"Microglia in neurodegenerative disease","volume":"6","author":"Perry","year":"2010","journal-title":"Nat. Rev. Neurol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/nrn3722","article-title":"Microglia and brain macrophages in the molecular age: From origin to neuropsychiatric disease","volume":"15","author":"Prinz","year":"2014","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e135","DOI":"10.1212\/NXG.0000000000000135","article-title":"Redefining the phenotype of ALSP and AARS2 mutation\u2013related leukodystrophy","volume":"3","author":"Lakshmanan","year":"2017","journal-title":"Neurol. Genet."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"119","DOI":"10.5607\/en.2019.28.1.119","article-title":"An Autopsy Proven Case of CSF1R-mutant Adult-onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP) with Premature Ovarian Failure","volume":"28","author":"Kim","year":"2019","journal-title":"Exp. Neurobiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jocn.2017.10.060","article-title":"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)","volume":"48","author":"Adams","year":"2018","journal-title":"J. Clin. Neurosci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1212\/01.wnl.0000304045.99153.8f","article-title":"Sporadic adult-onset leukoencephalopathy with neuroaxonal spheroids mimicking cerebral MS","volume":"70","author":"Keegan","year":"2008","journal-title":"Neurology"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.clineuro.2014.04.022","article-title":"Diffuse leukoencephalopathy with spheroids: Biopsy findings and a novel mutation","volume":"122","author":"Levin","year":"2014","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_109","first-page":"308","article-title":"Sporadic adult-onset leucodystrophy with axonal spheroids and pigmented glia with no mutations in the known targeted genes","volume":"68","author":"Imizcoz","year":"2015","journal-title":"Histopathology"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"792840","DOI":"10.3389\/fnagi.2021.792840","article-title":"Recent Advances in Basic Research for CSF1R-Microglial Encephalopathy","volume":"13","author":"Wang","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_111","first-page":"626","article-title":"Two cases of cystic bone disease showing peculiar features","volume":"35","author":"Terayama","year":"1961","journal-title":"Nippon Seikeigeka Gakkai Zasshi"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.1600-0404.1970.tb02161.x","article-title":"Osteodysplasia polycystica hereditaria combined with sclerosing leucoencephalopathy","volume":"46","author":"Hakola","year":"2009","journal-title":"Acta Neurol. Scand."},{"key":"ref_113","first-page":"1","article-title":"Neuropsychiatric and genetic aspects of a new hereditary disease characterized by progressive dementia and lipomembranous polycystic osteodysplasia","volume":"232","author":"Hakola","year":"1972","journal-title":"Acta Psychiatr. Scand. Suppl."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1007\/BF00340444","article-title":"A new hereditary disease with progressive dementia and polycystic osteodysplasia: Neuroradiological analysis of seven cases","volume":"6","author":"Hakola","year":"1973","journal-title":"Neuroradiology"},{"key":"ref_115","first-page":"539","article-title":"A lipid metabolic disease\u2014\u201cMembranous lipodystrophy\u201d\u2014An autopsy case demonstrating numerous peculiar membrane-structures composed of compound lipid in bone and bone marrow and various adipose tissues","volume":"23","author":"Nasu","year":"1973","journal-title":"Acta Pathol. Jpn."},{"key":"ref_116","first-page":"169","article-title":"A case of \u201cmembranous lipodystrophy (Nasu)\u201d with emphasis on psychiatric and neuropathologic aspects","volume":"29","author":"Harada","year":"1975","journal-title":"Folia Psychiatr. Neurol. Jpn."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/BF00361370","article-title":"Radiologic bone changes of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy","volume":"8","author":"Hakola","year":"1982","journal-title":"Skelet. Radiol."},{"key":"ref_118","first-page":"38","article-title":"Membranous lipodystrophy (Nasu disease): Clinical and neuropathological study of a case","volume":"4","author":"Minagawa","year":"1985","journal-title":"Clin. Neuropathol."},{"key":"ref_119","unstructured":"Henriksson, M., Huttunen, M., Kuoppasalmi, K., Lindfors, O., and Lonnqvist, J. (1990). Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (membranous lipodystrophy): A neuropsychiatric follow-up study, Monographs of Psychiatria Fennica."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1159\/000282479","article-title":"Membranous Lipodystrophy (Nasu\u2019s Disease): A Rare Cause of Neuropathic Urinary Incontinence","volume":"50","author":"Ishigooka","year":"1993","journal-title":"Urol. Int."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1136\/jmg.34.9.753","article-title":"Nasu-Hakola syndrome: Polycystic lipomembranous osteodysplasia with sclerosing leucoencephalopathy and presenile dementia","volume":"34","author":"Verloes","year":"1997","journal-title":"J. Med. Genet."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1212\/WNL.56.11.1552","article-title":"CNS manifestations of Nasu-Hakola disease: A frontal dementia with bone cysts","volume":"56","author":"Bm","year":"2001","journal-title":"Neurology"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1023\/B:CEMN.0000012721.08168.ee","article-title":"Nasu-Hakola disease (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy\u2014PLOSL): A dementia associated with bone cystic lesions. From clinical to genetic and molecular aspects","volume":"24","author":"Bianchin","year":"2004","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/j.1440-1789.2010.01127.x","article-title":"Nasu-Hakola disease: The first case reported by Nasu and review: The 50th An-niversary of Japanese Society of Neuropathology","volume":"30","author":"Kaneko","year":"2010","journal-title":"Neuropathology"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1111\/j.1601-5215.2011.00626.x","article-title":"Rorschach assessment of personality functioning in patients with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy","volume":"24","author":"Ilonen","year":"2012","journal-title":"Acta Neuropsychiatr."},{"key":"ref_126","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Stephens, K., and Amemiya, A. (2020). Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). GeneReviews\u00ae [Internet], University of Washington."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/0022-510X(89)90074-9","article-title":"Nasu-Hakola disease (membranous lipodystrophy): Clinical, histopathological and biochemical studies of three cases","volume":"91","author":"Kitajima","year":"1989","journal-title":"J. Neurol. Sci."},{"key":"ref_128","first-page":"71","article-title":"Neuropsychological tests and functional nuclear neuroim-aging provide evidence of subclinical impairment in Nasu-Hakola disease heterozygotes","volume":"20","author":"Montalbetti","year":"2005","journal-title":"Funct. Neurol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"E194","DOI":"10.1002\/humu.20836","article-title":"Mutations in TREM2 lead to pure early-onset dementia without bone cysts","volume":"29","author":"Chouery","year":"2008","journal-title":"Hum. Mutat."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2890.e1","DOI":"10.1016\/j.neurobiolaging.2013.06.005","article-title":"A novel compound heterozygous mutation in TREM2 found in a Turkish frontotemporal dementia-like family","volume":"34","author":"Guerreiro","year":"2013","journal-title":"Neurobiol. Aging"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1001\/jamaneurol.2013.579","article-title":"Using Exome Sequencing to Reveal Mutations in TREM2 Presenting as a Frontotemporal Dementia\u2013like Syndrome Without Bone Involvement","volume":"70","author":"Guerreiro","year":"2013","journal-title":"JAMA Neurol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jns.2013.01.021","article-title":"Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL): A new report of an Italian woman and review of the literature","volume":"326","author":"Bock","year":"2013","journal-title":"J. Neurol. Sci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2419.e23","DOI":"10.1016\/j.neurobiolaging.2014.04.010","article-title":"Homozygous TREM2 mutation in a family with atypical frontotemporal dementia","volume":"35","author":"Guerreiro","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/BF00343833","article-title":"Membranous lipodystrophy. A case report","volume":"231","author":"Matsuo","year":"1982","journal-title":"Arch Psychiatr. Nervenkr."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1007\/s00256-014-1887-5","article-title":"Membranous lipodystrophy: Skeletal findings on CT and MRI","volume":"43","author":"Nwawka","year":"2014","journal-title":"Skelet. Radiol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1136\/jnnp.46.6.515","article-title":"Neurophysiological findings in the hereditary presenile dementia characterised by polycystic lipomembranous osteodysplasia and sclerosing leukoencephalopathy","volume":"46","author":"Hakola","year":"1983","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1212\/WNL.33.1.81","article-title":"Lipomembranous polycystic osteodysplasia (brain, bone, and fat disease): A genetic cause of presenile dementia","volume":"33","author":"Bird","year":"1983","journal-title":"Neurology"},{"key":"ref_138","first-page":"1232","article-title":"A case of membranous lipodystrophy (Nasu) with diffuse cerebral, white matter involvement and cerebellar atrophy on brain CT and NM (in Japanese)","volume":"30","author":"Shibata","year":"1990","journal-title":"Rinsho Shinkeigaku"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1148\/radiology.180.3.1871295","article-title":"Membranous lipodystrophy: MR imaging appearance of the brain","volume":"180","author":"Araki","year":"1991","journal-title":"Radiology"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s13760-018-1023-8","article-title":"Early-onset dementia, leukoencephalopathy and brain calcifications: A clinical, imaging and pathological comparison of ALSP and PLOSL\/Nasu Hakola disease","volume":"118","author":"Coomans","year":"2018","journal-title":"Acta Neurol. Belg."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/BF02984623","article-title":"Regional cerebral blood flow in a patient with Nasu-Hakola disease","volume":"19","author":"Takeshita","year":"2005","journal-title":"Ann. Nucl. Med."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1212\/01.WNL.0000160304.00003.CA","article-title":"The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2","volume":"64","author":"Klunemann","year":"2005","journal-title":"Neurology"},{"key":"ref_143","first-page":"281","article-title":"Membranous lipodystrophy. Light and electron microscopic study of a biopsy case","volume":"37","author":"Sageshima","year":"1987","journal-title":"Acta Pathol. Jpn."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/BF01605140","article-title":"Degenerative change of adipose tissue; the so-called membranous lipodystrophy","volume":"416","author":"Machinami","year":"1990","journal-title":"Virchows Arch."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/BF01600227","article-title":"Ultrastructural lipid and glycoconjugate cytochemistry of membranous lipodystrophy (Nasu-Hakola disease)","volume":"419","author":"Mii","year":"1991","journal-title":"Virchows Arch."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.bone.2018.10.008","article-title":"Bone matrix hypermineralization associated with low bone turnover in a case of Nasu-Hakola disease","volume":"123","author":"Shboul","year":"2018","journal-title":"Bone"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/BF00707983","article-title":"Membranocystic lesions of the lung in Nasu-Hakola disease","volume":"408","author":"Yagishita","year":"1985","journal-title":"Virchows Arch."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1046\/j.1440-1789.2000.00297.x","article-title":"Nasu-Hakola disease: A review of its leukoencephalopathic and membranolipodystrophic features","volume":"20","author":"Tanaka","year":"2000","journal-title":"Neuropathology"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/j.1440-1789.2010.01152.x","article-title":"Gray matter lesions in Nasu-Hakola disease: A report on three autopsy cases","volume":"31","author":"Aoki","year":"2010","journal-title":"Neuropathology"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1111\/j.1600-0404.1994.tb02646.x","article-title":"Vascular changes and blood-brain barrier damage in the pathogenesis of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (membranous lipodystrophy)","volume":"89","author":"Kalimo","year":"1994","journal-title":"Acta. Neurol. Scand."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/BF00689400","article-title":"Nasu-Hakola\u2019s disease (membranous lipodystrophy)","volume":"54","author":"Matsushita","year":"1981","journal-title":"Acta Neuropathol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1007\/BF00296554","article-title":"Membranous lipodystrophy (Nasu-Hakola disease) with thalamic degeneration: Report of an autopsied case","volume":"82","author":"Miyazu","year":"1991","journal-title":"Acta Neuropathol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"32","DOI":"10.5582\/irdr.2017.01088","article-title":"Alzheimer\u2019s disease pathology in Nasu-Hakola disease brains","volume":"7","author":"Satoh","year":"2018","journal-title":"Intractable Rare Dis. Res."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3233\/JAD-201085","article-title":"Neuropathological Alzheimer\u2019s Disease Lesions in Nasu-Hakola Disease with TREM2 Mutation: Atypical Distribution of Neurofibrillary Changes","volume":"79","author":"Maderna","year":"2021","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1440-1819.1989.tb03104.x","article-title":"Fatty Acid Analysis of Galactolipids and Ganglioside in the Brains of Four Cases of Nasu-Hakola Disease","volume":"43","author":"Yokoi","year":"1989","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_156","first-page":"49","article-title":"Pheripheral motor-sensory neuropathy in membranous lipodystrophy (Nasu\u2019s disease): A case report","volume":"11","author":"Iannaccone","year":"1992","journal-title":"Clin. Neuropathol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/77153","article-title":"Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts","volume":"25","author":"Paloneva","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1086\/342259","article-title":"Mutations in Two Genes Encoding Different Subunits of a Receptor Signaling Complex Result in an Identical Disease Phenotype","volume":"71","author":"Paloneva","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1212\/WNL.59.7.1105","article-title":"Heterogeneity of presenile dementia with bone cysts (Nasu-Hakola disease): Three genetic forms","volume":"59","author":"Kondo","year":"2002","journal-title":"Neurology"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1136\/jnnp.74.6.825-a","article-title":"An Italian family affected by Nasu-Hakola disease with a novel genetic mutation in the TREM2 gene","volume":"74","author":"Soragna","year":"2003","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1111\/j.1468-1331.2010.03311.x","article-title":"Nasu-Hakola disease with a splicing mutation of TREM2 in a Japanese family","volume":"18","author":"Numasawa","year":"2010","journal-title":"Eur. J. Neurol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"194.e13","DOI":"10.1016\/j.neurobiolaging.2017.01.015","article-title":"A novel mutation in TREM2 gene causing Nasu-Hakola disease and review of the literature","volume":"53","author":"Dardiotis","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/j.jmb.2017.04.004","article-title":"TREM2-Ligand Interactions in Health and Disease","volume":"429","author":"Kober","year":"2017","journal-title":"J. Mol. Biol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"5083","DOI":"10.4049\/jimmunol.158.11.5083","article-title":"Killer-cell activatory receptors for MHC class I mole-cules are included in a multimeric complex expressed by human killer cells","volume":"158","author":"Olcese","year":"1997","journal-title":"J. Immunol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/35642","article-title":"Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells","volume":"391","author":"Lanier","year":"1998","journal-title":"Nature"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"34115","DOI":"10.1074\/jbc.273.51.34115","article-title":"Gene Structure, Expression Pattern, and Biological Activity of Mouse Killer Cell Activating Receptor-associated Protein (KARAP)\/DAP-12","volume":"273","author":"Tomasello","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1002\/(SICI)1521-4141(199802)28:02<599::AID-IMMU599>3.0.CO;2-F","article-title":"Signaling through human killer cell activating receptors triggers tyrosine phosphorylation of an associated protein complex","volume":"28","author":"Campbell","year":"1998","journal-title":"Eur. J. Immunol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1002\/eji.200425932","article-title":"KARAP\/DAP12\/TYROBP: Three names and a multiplicity of biological functions","volume":"35","author":"Tomasello","year":"2005","journal-title":"Eur. J. Immunol."},{"key":"ref_169","first-page":"89","article-title":"The TREM2-DAP12 signaling pathway in Nasu\u2013Hakola disease: A molecular genetics perspective","volume":"5","author":"Humphrey","year":"2015","journal-title":"Res. Rep. Biochem."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1440-1789.2011.01256.x","article-title":"Phosphorylated Syk expression is enhanced in Nasu-Hakola disease brains","volume":"32","author":"Satoh","year":"2012","journal-title":"Neuropathology"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1084\/jem.20022220","article-title":"Impaired Differentiation of Osteoclasts in TREM-2\u2013deficient Individuals","volume":"198","author":"Cella","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1084\/jem.20030027","article-title":"DAP12\/TREM2 Deficiency Results in Impaired Osteoclast Differentiation and Osteoporotic Features","volume":"198","author":"Paloneva","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1172\/JCI16923","article-title":"Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice","volume":"111","author":"Kaifu","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1359\/JBMR.051016","article-title":"TREM2, a DAP12-Associated Receptor, Regulates Osteoclast Differentiation and Function","volume":"21","author":"Humphrey","year":"2005","journal-title":"J. Bone Miner. Res."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S0002-9440(10)62251-1","article-title":"Brain and Bone Damage in KARAP\/DAP12 Loss-of-Function Mice Correlate with Alterations in Microglia and Osteoclast Lineages","volume":"166","author":"Nataf","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1007\/s11064-008-9657-1","article-title":"Developmental Regulation of TREM2 and DAP12 Expression in the Murine CNS: Implications for Nasu-Hakola Disease","volume":"34","author":"Thrash","year":"2008","journal-title":"Neurochem. Res."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nri1106","article-title":"TREMs in the immune system and beyond","volume":"3","author":"Colonna","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.coi.2009.01.009","article-title":"TREM and TREM-like receptors in inflammation and disease","volume":"21","author":"Ford","year":"2009","journal-title":"Curr. Opin. Immunol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.neuropharm.2016.01.028","article-title":"TREM2 modifies microglial phenotype and provides neuroprotection in P301S tau transgenic mice","volume":"105","author":"Jiang","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.15252\/embr.201743922","article-title":"TREM 2 deficiency impairs chemotaxis and microglial responses to neuronal injury","volume":"18","author":"Mazaheri","year":"2017","journal-title":"EMBO Rep."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1016\/j.stemcr.2018.03.003","article-title":"Functional Studies of Missense TREM2 Mutations in Human Stem Cell-Derived Microglia","volume":"10","author":"Brownjohn","year":"2018","journal-title":"Stem Cell Rep."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/j.1440-1789.2010.01174.x","article-title":"Immunohistochemical characterization of microglia in Nasu-Hakola disease brains","volume":"31","author":"Satoh","year":"2011","journal-title":"Neuropathology"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1111\/neup.12222","article-title":"Immunohistochemical characterization of CD33 expression on microglia in Nasu-Hakola disease brains","volume":"35","author":"Satoh","year":"2015","journal-title":"Neuropathology"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s10048-015-0451-3","article-title":"Variable expression of microglial DAP12 and TREM2 genes in Nasu-Hakola disease","volume":"16","author":"Sasaki","year":"2015","journal-title":"Neurogenetics"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"275","DOI":"10.5582\/irdr.2016.01086","article-title":"Expression of gp91phox and p22phox, catalytic subunits of NADPH oxidase, on microglia in Nasu-Hakola disease brains","volume":"5","author":"Satoh","year":"2016","journal-title":"Intractable Rare Dis. Res."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"4957","DOI":"10.1038\/srep04957","article-title":"Direct induction of ramified microglia-like cells from human monocytes: Dynamic microglial dysfunction in Nasu-Hakola disease","volume":"4","author":"Ohgidani","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s13024-020-00409-0","article-title":"Trem2 Y38C mutation and loss of Trem2 impairs neuronal synapses in adult mice","volume":"15","author":"Jadhav","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"50","DOI":"10.5582\/irdr.2016.01097","article-title":"Expression of GPR17, a regulator of oligodendrocyte differentiation and maturation, in Nasu-Hakola disease brains","volume":"6","author":"Satoh","year":"2017","journal-title":"Intractable Rare Dis. Res."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/1750-1172-9-68","article-title":"LC3, an autophagosome marker, is expressed on oligodendrocytes in Nasu-Hakola disease brains","volume":"9","author":"Satoh","year":"2014","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"11421","DOI":"10.1523\/JNEUROSCI.2251-04.2004","article-title":"Impaired Synaptic Function in the Microglial KARAP\/DAP12-Deficient Mouse","volume":"24","author":"Roumier","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.immuni.2018.04.016","article-title":"The Microglial Innate Immune Receptor TREM2 Is Required for Synapse Elimination and Normal Brain Connectivity","volume":"48","author":"Filipello","year":"2018","journal-title":"Immunity"},{"key":"ref_192","doi-asserted-by":"crossref","unstructured":"Mecca, C., Giambanco, I., Donato, R., and Arcuri, C. (2018). Microglia and Aging: The Role of the TREM2\u2013DAP12 and CX3CL1-CX3CR1 Axes. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010318"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/nri2014","article-title":"Activating and inhibitory functions of DAP12","volume":"7","author":"Turnbull","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"206","DOI":"10.3389\/fncel.2018.00206","article-title":"Microglial TREM2\/DAP12 Signaling: A Double-Edged Sword in Neural Diseases","volume":"12","author":"Konishi","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/s00401-020-02193-z","article-title":"TREM2 activation on microglia promotes myelin debris clearance and remyelination in a model of multiple sclerosis","volume":"140","author":"Cignarella","year":"2020","journal-title":"Acta Neuropathol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.nbd.2004.09.007","article-title":"Dap12 and Trem2, molecules involved in innate immunity and neurodegeneration, are co-expressed in the CNS","volume":"18","author":"Kiialainen","year":"2005","journal-title":"Neurobiol. Dis."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1111\/j.1460-9568.2004.03729.x","article-title":"Distribution and signaling of TREM2\/DAP12, the receptor system mutated in human polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy dementia","volume":"20","author":"Sessa","year":"2004","journal-title":"Eur. J. Neurosci."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1136\/jnnp-2018-319481","article-title":"Practical approach to the diagnosis of adult-onset leukodystrophies: An updated guide in the genomic era","volume":"90","author":"Lynch","year":"2018","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"788168","DOI":"10.3389\/fneur.2021.788168","article-title":"Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia: Review of Clinical Manifestations as Foundations for Therapeutic Development","volume":"12","author":"Papapetropoulos","year":"2022","journal-title":"Front. Neurol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/ene.15115","article-title":"Evaluation of CSF1R-related adult onset leukoencephalopathy with axonal spheroids and pigmented glia diagnostic criteria","volume":"29","author":"Ayrignac","year":"2021","journal-title":"Eur. J. Neurol."},{"key":"ref_201","first-page":"1375","article-title":"Haematopoietic stem cell transplantation in CSF1R-related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia","volume":"90","author":"Mochel","year":"2019","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1093\/brain\/awz390","article-title":"Allogeneic HSCT for adult-onset leukoencephalopathy with spheroids and pigmented glia","volume":"143","author":"Gelfand","year":"2019","journal-title":"Brain"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1002\/mds.28515","article-title":"Is Pre-Symptomatic Immunosuppression Protective in CSF1R-related Leukoencephalopathy?","volume":"36","author":"Tipton","year":"2021","journal-title":"Mov. Disord."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"2901","DOI":"10.1002\/mds.28734","article-title":"Treatment of CSF1R-Related Leukoencephalopathy: Breaking New Ground","volume":"36","author":"Tipton","year":"2021","journal-title":"Mov. Disord."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.3389\/fimmu.2019.01685","article-title":"Phenotypic Expansion in Nasu-Hakola Disease: Immunological Findings in Three Patients and Proposal of a Unifying Pathogenic Hypothesis","volume":"10","author":"Errichiello","year":"2019","journal-title":"Front. Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/11\/6341\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:25:08Z","timestamp":1760138708000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/11\/6341"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,6]]},"references-count":205,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["ijms23116341"],"URL":"https:\/\/doi.org\/10.3390\/ijms23116341","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,6]]}}}