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Nasu–Hakola Disease (Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy—PLOSL): A Dementia Associated with Bone Cystic Lesions. From Clinical to Genetic and Molecular Aspects

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Abstract

The authors review the clinical, radiological, electrophysiological, pathological, and molecular aspects of Nasu–Hakola disease (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy or PLOSL). Nasu-Hakola disease is a unique disease characterized by multiple bone cysts associated with a peculiar form of neurodegeneration that leads to dementia and precocious death usually during the fifth decade of life. The diagnosis can be established on the basis of clinical and radiological findings. Recently, molecular analysis of affected families revealed mutations in the DAP12 (TYROBP) or TREM2 genes, providing an interesting example how mutations in two different subunits of a multi-subunit receptor complex result in an identical human disease phenotype. The association of PLOSL with mutations in the DAP12 or TREM2 genes has led to improved diagnosis of affected individuals. Also, the possible roles of the DAP12/TREM2 signaling pathway in microglia and osteoclasts in humans are just beginning to be elucidated. Some aspects of this peculiar signaling pathway are discussed here.

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REFERENCES

  • Abrikossoff, A. (1929). Über das Schicksal der spontan auftretenden Fettgranulome (lipophagen Granulome). Verh. Dtsch. Ges. Pathol. 24:57-64.

    Google Scholar 

  • Ahn, S., Yoo, M., Lee, S., and Choi, E. (1996). A clinical and histopathological study of 22 patients with membranous lipodystrophy. Clin. Exp. Dermatol. 21:269-272.

    Google Scholar 

  • Akai, M., Tateishi, A., Cheng, C. H., Morii, K., Abe, M., Ohno, T., and Ben, M. (1977). Membranous lipodystrophy: A clinicopathological study of six cases. J. Bone Joint Surg. Am. 59:802-809.

    Google Scholar 

  • Albright, A. V., Shieh, J. T., Itoh, T., Lee, B., Pleasure, D., O'Connor, M. J., Doms, R. W., and Gonzalez-Scarano, F. (1999). Microglia express CCR5, CXCR4, and CCR3, but of these, CCR5 is the principal coreceptor for human immunodeficiency virus type 1 dementia isolates. J. Virol. 73:205-213.

    Google Scholar 

  • Amano, N., Iwabuchi, K., Sakai, H., Yagishita, S., Itoh, Y., Iseki, E., Yokoi, S., Arai, N., and Kinoshita, J. (1987). Nasu-Hakola's disease (membranous lipodystrophy). Acta Neuropathol. (Berl.) 74:294-299.

    Google Scholar 

  • Araki, T., Ohba, H., Monzawa, S., Sakuyama, K., Hachiya, J., Seki, T., Takahashi, Y., and Yamaguchi, M. (1991). Membranous lipodystrophy: MR imaging appearance of the brain. Radiology 180:793-797.

    Google Scholar 

  • Bacon, K. B., and Harrison, J. K. (2000). Chemokines and their receptors in neurobiology: Perspectives in physiology and homeostasis. J. Neuroimmunol. 104:92-97.

    Google Scholar 

  • Bakker, A. B., Baker, E., Sutherland, G. R., Phillips, J. H., and Lanier, L. L. (1999). Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor involved in the activation of myeloid cells. Proc. Natl. Acad. Sci. U.S.A. 96:9792-9796.

    Google Scholar 

  • Bakker, A. B., Hoek, R. M., Cerwenka, A., Blom, B., Lucian, L., McNeil, T., Murray, R., Phillips, L. H., Sedgwick, J. D., and Lanier, L. L. (2000). DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming. Immunity 13:345-353.

    Google Scholar 

  • Banchereau, J., and Steinman, R. M. (1998). Dendritic cells and the control of immunity. Nature. 19:245-252.

    Google Scholar 

  • Bird, T. D., Koerker, R. M., Leaird, B. J., Vlcek, B. W., and Thorning, D. R. (1983). Lipomembranous polycystic osteodysplasia (brain, bone, and fat disease): A genetic cause of presenile dementia. Neurology 33:81-86.

    Google Scholar 

  • Blair, H. C. (1998). How the osteoclast degrades bone. Bioessays 20:837-846.

    Google Scholar 

  • Blair, H. C., Zaidi, M., and Schlesinger, P. H. (2002). Mechanisms balancing skeletal matrix synthesis and degradation. Biochem. J. 364:329-341.

    Google Scholar 

  • Bouchon, A., Dietrich, J., and Colonna, M. (2000). Cutting edge: Inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes. J. Immunol. 164:4991-4995.

    Google Scholar 

  • Bouchon, A., Hernandez-Munain, C., Cella, M., and Colonna, M. (2001). A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells. J. Exp. Med. 194:1111-1122.

    Google Scholar 

  • Brown, D. R. (2001). Microglia and prion disease. Microsc. Res. Tech. 54:71-80.

    Google Scholar 

  • Campbell, K. S., and Colonna, M. (1999). DAP12: A key accessory protein for relaying signals by natural killer cell receptors. Int. J. Biochem. Cell. Biol. 31:631-636.

    Google Scholar 

  • Chabas, D., Baranzini, S. E., Mitchell, D., Bernard, C. C., Rittling, S. R., Denhardt, D. T., Sobel, R. A., Lock, C., Karpuj, M., Pedotti, R., Heller, R., Oksenberg, J. R., and Steinman, L. (2001). The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease. Science 294:1731-1735.

    Google Scholar 

  • Chung, D. H., Seaman, W. E., and Daws, M. R. (2002). Characterization of TREM-3, an activating receptor on mouse macrophages: Definition of a family of single Ig domain receptors on mouse chromosome 17. Eur. J. Immunol. 32:59-66.

    Google Scholar 

  • Compston, J. E. (2002). Bone marrow and bone: A functional unit. J. Endocrinol. 173:387-394.

    Google Scholar 

  • Coraci, I. S., Husemann, J., Berman, J. W., Hulette, C., Dufour, J. H., Campanella, G. K., Luster, A. D., Silverstein, S. C., and El-Khoury, J. B. (2002). CD36, a class B scavenger receptor, is expressed on microglia in Alzheimer's disease brains and can mediate production of reactive oxygen species in response to beta-amyloid fibrils. Am. J. Pathol. 160:101-112.

    Google Scholar 

  • Cummings, J. L. (1986). Subcortical dementia. Neuropsychology, neuropsychiatry, and pathophysiology. Br. J. Psychiatr 149:682-697.

    Google Scholar 

  • Diefenbach, A., Tomasello, E., Lucas, M., Jamieson, A. M., Hsia, J. K., Vivier, E., and Raulet, D. H. (2002). Selective associations with signaling proteins determine stimulatory versus costimulatory activity of NKG2D. Nat. Immunol. 3:1142-1149.

    Google Scholar 

  • Deisenhammer, F., Willeit, J., Schmidauer, C., Kiechl, S., and Pohl, P. (1993). [Membranous lipodystrophy (Nasu-Hakola disease)]. Nervenarzt. 64:263-265.

    Google Scholar 

  • Dietrich, J., Cella, M., Seiffert, M., Buhring, H. J., and Colonna, M. (2000). Cutting edge: Signal-regulatory protein beta 1 is a DAP12-associated activating receptor expressed in myeloid cells. J. Immunol. 164:9-12.

    Google Scholar 

  • Ducy, P., Schinke, T., and Karsenty, G. (2000). The osteoblast: A sophisticated fibroblast under central surveillance. Science 289:1501-1504.

    Google Scholar 

  • Duong, L. T., and Rodan, G. A. (2001). Regulation of osteoclast formation and function. Ver. Endocr. Metab. Disord. 2:95-104.

    Google Scholar 

  • Gallucci, S., Lolkema, M., and Matzinger, P. (1999). Natural adjuvants: Endogeneous activators of dendritic cells. Nat. Med. 11:1249-1255.

    Google Scholar 

  • Gebicke-Haerter, P. J. (2001). Microglia in neurodegeneration: Molecular aspects. Microsc. Res. Tech. 54:47-58.

    Google Scholar 

  • Gebicke-Haerter, P. J., Spleiss, O., Ren, L. Q., Li, H., Dichmann, S., Norgauer, J., and Boddeke, H. W. (2001). Microglial chemokines and chemokine receptors. Prog. Brain Res. 132:525-532.

    Google Scholar 

  • Gebicke-Haerter, P. J., Van Calker, D., Norenberg, W., and Illes, P. (1996). Molecular mechanisms of microglial activation. plications for regeneration and neurodegenerative diseases. Neurochem. Int. 29:1-12.

    Google Scholar 

  • Gilfillan, S., Ho, E. L., Cella, M., Yokoyama, W. M., and Colonna, M. (2002). NKG2D recruits two distinct adapters to trigger NK cell activation and costimulation. Nat. Immunol. 3:1150-1155.

    Google Scholar 

  • Gonzalez-Scarano, F., and Baltuch, G. (1999). Microglia as mediators of inflammatory and degenerative diseases. Annu. Rev. Neurosci. 22:219-240.

    Google Scholar 

  • Greenfield, E. M., Bi, Y., and Miyauchi, A. (1999). Regulation of osteoclast activity. Life Sci. 65:1087-1102.

    Google Scholar 

  • Hakola, H. P. (1972). Neuropsychiatric and genetic aspects of a new hereditary disease characterized by progressive dementia and lipomembranous polycystic osteodysplasia. Acta Psychiatr. Scand. Suppl. 232:1-173.

    Google Scholar 

  • Hakola, H. P., and Karjalanen, P. (1975). Bone mineral content in hereditary polycystic osteodysplasia associated with progressive dementia. Acta. Radiol. Diagn. 16:385-392.

    Google Scholar 

  • Hakola, H. P. (1998). Benton's Visual Retention Test in patients with polycystic lipomembranous dysplasia with sclerosing leukoencephalopathy. Dement. Geriatr. Cogn. Disord. 9:39-43.

    Google Scholar 

  • Hakola, H. P., Jarvi, O. H., and Sourander, P. (1970). Osteodysplasia polycystica hereditaria combined with sclerosing leucoencephalopathy, a new entity of the dementia praesenilis group. Acta Neurol. Scand. 46(Suppl 43):79.

    Google Scholar 

  • Hakola, H. P., Karjalainen, P., and Virtama, P. (1988). Bone scintigraphy in polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy. Nucl. Med. Commun. 9:1005-1011.

    Google Scholar 

  • Hakola, H. P., and Partanen, V. S. (1983). Neurophysiological findings in the hereditary presenile dementia characterised by polycystic lipomembranous osteodysplasia and sclerosing leukoencephalopathy. J. Neurol. Neurosurg. Psychiatry 46:515-520.

    Google Scholar 

  • Hakola, H. P., and Puranen, M. (1993). Neuropsychiatric and brain CT findings in polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy. Acta Neurol. Scand. 88:370-375.

    Google Scholar 

  • Halliday, G., Robinson, S. R., Shepherd, C., and Kril, J. (2000). Alzheimer's disease and inflammation: A review of cellular and therapeutic mechanisms. Clin. Exp. Pharmacol. Physiol. 27:1-8.

    Google Scholar 

  • Harada, K. (1975). [A case of “membranous lipodystrophy (Nasu)” with emphasis on psychiatric and neuropathologic aspects (Author's Transl.)]. Folia Psychiatr. Neurol. Jpn. 29:169-177.

    Google Scholar 

  • Hasegawa, Y., and Inagaki, Y. (1983). Membranous lipodystrophy (lipomembranous polycystic osteodysplasia). Two case reports. Clin. Orthop. 12:229-232.

    Google Scholar 

  • Hill, P. A. (1998). Bone remodelling. Br. J. Orthod. 25:101-107.

    Google Scholar 

  • Hull, M., Lieb, K., and Fiebich, B. L. (2002). Pathways of inflammatory activation in Alzheimer's disease: Potential targets for disease modifying drugs. Curr. Med. Chem. 9:83-88.

    Google Scholar 

  • Kalimo, H., Sourander, P., Jarvi, O., and Hakola, P. (1994). Vascular changes and blood-brain barrier damage in the pathogenesis of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (membranous lipodystrophy). Acta Neurol. Scand. 89:353-361.

    Google Scholar 

  • Kaul, M., Garden, G. A., and Lipton, S. A. (2001). Pathways to neuronal injury and apoptosis in HIV-associated dementia. Nature 410:988-994.

    Google Scholar 

  • Kaul, M., and Lipton, S. A. (1999). Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis. Proc. Natl. Acad. Sci. U.S.A. 96:8212-8216.

    Google Scholar 

  • Kenny, A. M., and Raisz, L. G. (2002). Mechanisms of bone remodeling: Implications for clinical practice. J. Reprod. Med. 47:63-70.

    Google Scholar 

  • Kitajima, I., Kuriyama, M., Usuki, F., Izumo, S., Osame, M., Suganuma, T., Murata, F., and Nagamatsu, K. (1989). Nasu-Hakola disease (membranous lipodystrophy). Clinical, histopathological and biochemical studies of three cases. J. Neurol. Sci. 91:35-52.

    Google Scholar 

  • Kocer, N., Dervisoglu, S., Ersavasti, G., Altug, A., and Cokyuksel, O. (1994). Case report 867. Membranous lipodystrophy (polycystic lipomembranous osteodysplasia). Skeletal Radiol 23:577-579.

    Google Scholar 

  • Kondo, T., Takahashi, K., Kohara, N., Takahashi, Y., Hayashi, S., Takahashi, H., Matsuo, H., Yamazaki, M., Inoue, K., Miyamoto, K., and Yamamura, T. (2002). Heterogeneity of presenile dementia with bone cysts (Nasu-Hakola disease). Three genetic forms. Neurology 59:1105-1107.

    Google Scholar 

  • Langford, D., and Masliah, E. (2001). Crosstalk between components of the blood brain barrier and cells of the CNS in microglial activation in AIDS. Brain Pathol. 11:306-312.

    Google Scholar 

  • Lanier, L. L. (1998). NK cell receptors. Annu. Rev. Immunol. 16:359-393.

    Google Scholar 

  • Lanier, L. L., and Bakker, A. B. (2000). The ITAM-bearing transmembrane adaptor DAP12 in lymphoid and myeloid cell function. Immunol. Today 21:611-614.

    Google Scholar 

  • Lanier, L. L., Corliss, B., Wu, J., and Phillips, J. H. (1998a). Association of DAP12 with activating CD94/NKG2C NK cell receptors. Immunity 8:693-701.

    Google Scholar 

  • Lanier, L. L., Corliss, B. C., Wu, J., Leong, C., and Phillips, J. H. (1998b). Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells. Nature. 391:703-707.

    Google Scholar 

  • Machinami, R. (1984). Incidence of membranous lipodystrophy-like change among patients with limb necrosis caused by chronic arterial obstruction. Arch. Pathol. Lab. Med. 108:823-826.

    Google Scholar 

  • Machinami, R. (2001). [Membranous lipodystrophy of the bone]. Ann. Pathol. 21:524-528.

    Google Scholar 

  • Malandrini, A., Scarpini, C., Palmeri, S., Villanova, M., Parrotta, E., Tripodi, S., Giani, S., DeFalco, D., and Guazzi, G. C. (1996). Palatal myoclonus and unusual MRI findings in a patient with membranous lipodystrophy. Brain. Dev. 18:59-63.

    Google Scholar 

  • Manolagas, S. C. (2000). Birth and death of bone cells: Basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr. Rev. 21:115-137.

    Google Scholar 

  • Matsushita, M., Oyanagi, S., Hanawa, S., Shiraki, H., and Kosaka, K. (1981). Nasu-Hakola's disease (membranous lipodystrophy). A case report. Acta Neuropathol. (Berl.) 54:89-93.

    Google Scholar 

  • McVicar, D. W., Taylor, L. S., Gosselin, P., Willette-Brown, J., Mikhael, A. I., Geahlen, R. L., Nakamura, M. C., Linnemeyer, P., Seaman, W. E., Anderson, S. K., Ortaldo, J. R., and Mason, L. H. (1998). DAP12-mediated signal transduction in natural killer cells. A dominant role for the Syk protein-tyrosine kinase. J. Biol. Chem. 273:32934-32942.

    Google Scholar 

  • Merrill, J. E. (1992). Proinflammatory and antiinflammatory cytokines in multiple sclerosis and central nervous system acquired immunodeficiency syndrome. J. Immunother. 12:167-170.

    Google Scholar 

  • Minagar, A., Shapshak, P., Fujimura, R., Ownby, R., Heyes, M., and Eisdorfer, C. (2002). The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis. J. Neurol. Sci. 202:13.

    Google Scholar 

  • Mitrovic, B., Martin, F. C., Charles, A. C., Ignarro, L. J., Anton, P. A., Shanahan, F., and Merrill, J. E. (1994). Neurotransmitters and cytokines in CNS pathology. Prog. Brain. Res. 103:319-330.

    Google Scholar 

  • Miyazu, K., Kobayashi, K., Fukutani, Y., Nakamura, I., Hasegawa, H., Yamaguchi, N., and Saitoh, T. (1991). Membranous lipodystrophy (Nasu-Hakola disease) with thalamic degeneration: Report of an autopsied case. Acta Neuropathol. (Berl.) 82:414-419.

    Google Scholar 

  • Moretta, A., Bottino, C., Vitale, M., Pende, D., Cantoni, C., Mingari, M. C., et al. (2001). Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu. Ver. Immunol. 19:197-223.

    Google Scholar 

  • Motohashi, N., Shinohara, M., Shioe, K., Fukuzawa, H., Akiyama, Y., and Kariya, T. (1995). A case of membranous lipodystrophy (Nasu-Hakola disease) with unique MRI findings. Neuroradiology 37:549-550.

    Google Scholar 

  • Nakamura, Y. (2002). Regulating factors for microglial activation. Biol. Pharm. Bull. 25:945-953.

    Google Scholar 

  • Nasu, T., Tsukahara, Y., and Terayama, K. (1973). A lipid metabolic disease--“membranous lipodystrophy”--an autopsy case demonstrating numerous peculiar membrane-structures composed of compound lipid in bone and bone marrow and various adipose tissues. Acta Pathol. Jpn. 23:539-558.

    Google Scholar 

  • Ohtani, Y., Miura, S., Tamai, Y., Kojima, H., and Kashima, H. (1979). Neutral lipid and sphingolipid composition of the brain of a patient with membranous lipodystrophy. J. Neurol. 220:77-82.

    Google Scholar 

  • Okada, K., Hoshi, N., Kawamura, K., Sato, K., and Yamamoto, M. (1999). Membranocystic lesion in lumbar yellow ligament. Spine. 24:1147-1150.

    Google Scholar 

  • Paloneva, J., Autti, T., Raininko, R., Partanen, J., Salonen, O., Puranen, M., Hakola, P., and Haltia, M. (2001). CNS manifestations of Nasu-Hakola disease: A frontal dementia with bone cysts. Neurology 56:1552-1558.

    Google Scholar 

  • Paloneva, J., Kestila, M., Wu, J., Salminen, A., Bohling, T., Ruotsalainen, V., Hakola, P., Bakker, A. B., Phillips, J. H., Pekkarinen, P., Lanier, L. L., Timonen, T., and Peltonen, L. (2000). Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts. Nat. Genet. 25:357-361.

    Google Scholar 

  • Paloneva, J., Manninen, T., Christman, G., Hovanes, K., Mandelin, J., Adolfsson, R., Bianchin, M., Bird, T., Miranda, R., Salmaggi, A., Tranebjaerg, L., Konttinen, Y., and Peltonen, L. (2002). Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype. Am. J. Hum. Genet. 71:656-662.

    Google Scholar 

  • Pazzaglia, U. E., Benazzo, F., Byers, P. D., Riboni, L., and Ceciliani, L. (1987). Pathogenesis of membranous lipodystrophy. Case report and review of the literature. Clin. Orthop. 279-287.

  • Pekkarinen, P., Hovatta, I., Hakola, P., Jarvi, O., Kestila, M., Lenkkeri, U., Adolfsson, R., Holmgren, G., Nylander, P. O., Tranebjaerg, L., Terwilliger, J. D., Lonnqvist, J., and Peltonen, L. (1998). Assignment of the locus for PLO-SL, a frontal-lobe dementia with bone cysts, to 19q13. Am. J. Hum. Genet. 62:362-372.

    Google Scholar 

  • Preziuso, L., Muncibi, F., and Aglietti, F. G. (1992). A case of membranous lipodystrophy with skeletal involvement. Chir. Organi. Mov. 77:205-211.

    Google Scholar 

  • Sageshima, M., Masuda, H., Kawamura, K., and Shozawa, T. (1987). Membranous lipodystrophy. Light and electron microscopic study of a biopsy case. Acta Pathol. Jpn. 37:281-290.

    Google Scholar 

  • Sami, S., Liu, G., Hornicek, F., Cates, J. M., and Mankin, H. J. (2002). Membranous lipodystrophy. A case report. J. Bone Joint Surg. Am. 84-A:630-633.

    Google Scholar 

  • Sauter, B., Albert, M. L., Francisco, L., Larson, M., Somersoon, S., and Bhardwaj, N. (2000). Consequences of cell death: Exposure to necrotic tumor cells, but not primary cells or apoptotic cells, introduces the maturation of immunostimulatory dendritic cells. J. Exp. Med. 191:411-416.

    Google Scholar 

  • Schafer, C., Klunemann, H. H., Ibach, B., Mueller, J., Putzhammer, A., Trender-Gerhard, I., Schuierer, G., and Klein, H. E. (2002). [Presenile dementia in polycystic lipomembranous osteodysplasia]. Nervenarzt 73:879-882.

    Google Scholar 

  • Sjolin, H., Tomasello, E., Mousavi-Jazi, M., Bartolazzi, A., Karre, K., Vivier, E., and Cerboni, C. (2002). Pivotal role of KARAP/DAP12 adaptor molecule in the natural killer cell-mediated resistance to murine cytomegalovirus infection. J. Exp. Med. 195:825-834.

    Google Scholar 

  • Smith, K. M., Wu, J., Bakker, A. B., Phillips, J. H., and Lanier, L. L. (1998). Ly-49D and Ly-49H associate with mouse DAP12 and form activating receptors. J. Immunol. 161:7-10.

    Google Scholar 

  • Stubgen, J. P., and Lotz, B. P. (1992). Membranous lipodystrophy. Clinical and electrophysiological observations in the first South African case. S. Afr. Med. J. 81:620-622.

    Google Scholar 

  • Tanaka, J. (1980). Leukoencephalopathic alteration in membranous lipodystrophy. Acta Neuropathol. (Berl.) 50:193-197.

    Google Scholar 

  • Tanaka, J. (2000). Nasu-Hakola disease: A review of its leukoencephalopathic and membranolipodystrophic features. Neuropathology 20(Suppl):S25-S29.

    Google Scholar 

  • Teitelbaum, S. L. (2000). Bone resorption by osteoclasts. Science 289:1504-1508.

    Google Scholar 

  • Teitelbaum, S. L., Tondravi, M. M., and Ross, F. P. (1997). Osteoclasts, macrophages, and the molecular mechanisms of bone resorption. J. Leukoc. Biol. 61:381-388.

    Google Scholar 

  • Tomasello, E., Desmoulins, P.O., Chemin, K., Guia, S., Cremer, H., Ortaldo, J., Love, P., Kaiserlian, D., and Vivier, E. (2000). Combined natural killer cell and dendritic cell functional deficiency in KARAP/DAP12 loss-of-function mutant mice. Immunity 13:355-364.

    Google Scholar 

  • Tranebjaerg, L., Schrader, H., and Paloneva, J. (2000). [Polycystic lipomembranous osteodysplasia]. Tidsskr. Nor. Laegeforen. 120:3196.

    Google Scholar 

  • Ueki, Y., Kohara, N., Oga, T., Fukuyama, H., Akiguchi, I., Kimura, J., and Shibasaki, H. (2000). Membranous lipodystrophy presenting with palilalia: A PET study of cerebral glucose metabolism. Acta Neurol. Scand. 102:60-64.

    Google Scholar 

  • Vaananen, H. K., Zhao, H., Mulari, M., and Halleen, J. M. (2000). The cell biology of osteoclast function. J. Cell. Sci. 113(Pt. 3):377-381.

    Google Scholar 

  • Van Everbroeck, B., Dewulf, E., Pals, P., Lubke, U., Martin, J. J., and Cras, P. (2002). The role of cytokines, astrocytes, microglia and apoptosis in Creutzfeldt-Jakob disease. Neurobiol. Aging. 23:59-64.

    Google Scholar 

  • Verloes, A., Maquet, P., Sadzot, B., Vivario, M., Thiry, A., and Franck, G. (1997). Nasu-Hakola syndrome: Polycystic lipomembranous osteodysplasia with sclerosing leucoencephalopathy and presenile dementia. J. Med. Genet. 34:753-737.

    Google Scholar 

  • Wood, C. (1978). Membranous lipodystrophy of bone. Arch. Pathol. Lab. Med. 102:22-27.

    Google Scholar 

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Authors and Affiliations

  1. CIREP, Department of Neurology, Psychiatry and Medical Psychology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil

    Marino Muxfeldt Bianchin, Roger Walz, Carlos G. Carlotti Jr. & Américo C. Sakamoto

  2. Hospital Regional de São José Homero de Miranda Gomes, São José, Santa Catarina, Brazil

    Marino Muxfeldt Bianchin, Heraldo M. Capella, Daniel Loureiro Chaves, Gerson Gandi Ganev & Mônica Aparecida Poffo

  3. Diagnóstico Médico por Imagem—DMI, São José, Santa Catarina, Brazil

    Daniel Loureiro Chaves

  4. Hospital Governador Celso Ramos, Florianópolis, Santa Catarina, Brazil

    Daniel Loureiro Chaves & Evaldo Schaeffer Neto

  5. Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil

    Mário Steindel & Edmundo C. Grisard

  6. Departamento de Patologia, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil

    João Péricles da Silva Jr.

  7. Florianópolis, Laboratório de Anatomia Patológica Ltda—AP, Santa Catarina, Brazil

    João Péricles da Silva Jr.

  8. SONITEC—Diagnóstico Por Imagem, Florianópolis, Santa Catarina, Brazil

    Evaldo Schaeffer Neto

  9. Laboratory of Molecular Biology, Surgery Departament, Ribeirão Preto School of Medicine, University Hospital, University of São Paulo, Ribeirão, Preto, SP, Brazil

    Carlos G. Carlotti Jr.

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Bianchin, M.M., Capella, H.M., Chaves, D.L. et al. Nasu–Hakola Disease (Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy—PLOSL): A Dementia Associated with Bone Cystic Lesions. From Clinical to Genetic and Molecular Aspects. Cell Mol Neurobiol 24, 1–24 (2004). https://doi.org/10.1023/B:CEMN.0000012721.08168.ee

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