＜Late Breaking Symposium―2＞新たな若年性認知症：神経軸索ジストロフィーを伴う遺伝性白質脳症（HDLS）
遺伝性白質脳症とhereditary diffuse leukoencephalopathy with spheroids（HDLS）の分子病態
池内 健
新潟大学超域学術院・神経内科〔〒951―8585 新潟市中央区旭町通1―757〕
Adult-onset leukoencephalopathy involving the white matter of the brain is a heterogeneous disorder that exhibits a wide range of clinical manifestations. Recent advances in molecular genetics enable gene-based diagnosis of some forms of adult-onset leukoencephalopathy. In this review, the classification of adult-onset leukoencephalopathy based on molecular genetic findings is proposed. The autosomal dominant forms of adult-onset leukoencephalopathy include hereditary diffuse leukoencephalopathy with spheroids (HDLS), autosomal dominant adultonset leukoencephalopathy (ALDL), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and Alexander disease. The autosomal recessive forms of adult-onset leukoencephalopathy include cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), vanishing white matter (VWM) with leukoencephalopathy, Nasu-Hakola disease, and metachromatic leukodystrophy (MDL). X-chromosome-linked disorders include fragile X-associated tremor and ataxia syndrome (FXTAS) and adrenoleukodystrophy (ALD). Identification of the genes responsible for adult-onset leukoencephalopathy provides an important clue for elucidation of molecular pathophysiology underlying white matter disorders. One example is the identification of mutations in colony stimulating factor 1 receptor (CSF-1R) in patients with HDLS. Missense and splice site mutations have been found in the tyrosine kinase domain of CSF-1R. CSF-1R is highly expressed in microglia in the brain. It has been demonstrated that mice depleted of CSF-1R exhibit loss of microglia in the brain. In addition, stimulation of IL-34, a ligand of CSF-1R, induces proliferation and activation of microglia. These findings raise an intriguing possibility that dysfunction of microglia may play a role in the pathogenesis of white matter lesions occurring in patients with HDLS.
Full Text of this Article in Japanese PDF (227K)
(臨床神経, 52：1386−1389, 2012)
key words：成人発症，遺伝性白質脳症，神経軸索スフェロイド，CSF-1R，ミクログリア
（受付日：2012年5月25日）
