• Shinji Ito, Masaki Takao, Toshio Fukutake, Hiroyuki Hatsuta, Sayaka Funabe, Nobuo Ito, Yutaka Shimoe, Toshiro Niki, Imaharu Nakano, Masashi Fukayama, and Shigeo Murayama.
• From the Department of Neuropathology (SI, MT, HH, SF, SM) and Department of Neurology (SM), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan; Department of Pathology (SI), Toranomon Hospital, Tokyo, Japan; Department of Neurology (MT), Saitama International Medical Center, Saitama Medical University, Saitama, Japan; Department of Neurology (TF), Kameda Medical Center, Chiba, Japan; Department of Pathology (NI), Iida Municipal Hospital, Nagano, Japan; Department of Neurology (YS), Kashima Rosai Hospital, Ibaraki, Japan; Department of Integrative Pathology (TN) and Department of Neurology (IN), Jichi Medical University, Tochigi, Japan; and Department of Pathology (MF), The University of Tokyo, Graduate School of Medicine, Tokyo, Japan.
• J. Neuropathol. Exp. Neurol. 2016 Nov 1; 75 (11): 1020-1030.

AbstractCerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a nonhypertensive hereditary cerebral small vessel disease that is caused by mutations in a single gene, HTRA1. The HTRA1 protein normally represses transforming growth factor-β (TGF-β) signaling and its mutations result in vascular changes. Ten homozygous, 1 compound heterozygous, and 1 homozygous frameshift mutation have been identified in the HTRA1 gene of patients with genetically confirmed CARASIL. However, few studies have compared neuropathologic findings in patients with the same or different mutations in HTRA1. We analyzed histopathologic alterations in 3 autopsied patients with genetically confirmed CARASIL: 2 of them had the HTRA1 p.R302X mutation and 1 had the HTRA1 p.A252T mutation. All 3 had similar cerebral arteriopathy showing myointimal proliferation, multi-layering and splitting of elastic laminae, and marked loss of medial smooth muscle cells. One CARASIL patient with the p.R302X mutation had atherosclerosis-like intimal thickening and arteriolosclerosis in the arteries of visceral organs, indicating that atherosclerotic changes are not confined to the intracranial vasculature but can occur throughout the body. CARASIL is a unique hereditary disease that shows similar neuropathology, systemic vascular pathology, and other TGF-β1-related pathology associated with HTRA1 mutation.© 2016 American Association of Neuropathologists, Inc. All rights reserved.

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