Notch3 ectodomain is a major component of granular osmiophilic material (GOM) in CADASIL

Akira Ishiko, Atsushi Shimizu, Eiichiro Nagata, Keikichi Takahashi, Takeshi Tabira, Norihiro Suzuki

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited systemic vascular disorder characterized by recurrent subcortical ischemic strokes leading to vascular dementia. The gold standard to confirm the diagnosis is to identify a mutation in the underlying gene NOTCH3, encoding a transmembrane receptor protein. Granular osmiophilic material (GOM) deposition around vascular smooth muscle cells is a specific diagnostic feature of CADASIL and electron microscopic examination of a skin biopsy is another useful method for its diagnosis. Although accumulation of Notch3 ectodomain on the surface of vascular smooth muscle cells has been reported, the composition of GOM has not been elucidated. To elucidate the relationship between Notch3 protein and GOM, we performed postembedding immunogold electron microscopy using cryofixed and freeze substituted skin taken from two CADASIL patients. Our results demonstrate that GOM around vascular smooth muscle cells was specifically labeled with antibodies against the extracellular portion of Notch3 but not with antibodies recognizing the intracellular Notch3 domain. In non-CADASIL skin sections, no antibody binding was detected around the small dermal arteries. From these results, the major component of GOM in CADASIL patients is the ectodomain of the Notch3 gene product. Our results shed light on the relationship between Notch3 gene mutations and morphological deposition of GOM around the vascular smooth muscle cells.

Original languageEnglish
Pages (from-to)333-339
Number of pages7
JournalActa Neuropathologica
Volume112
Issue number3
DOIs
Publication statusPublished - 2006 Sep

Fingerprint

CADASIL
Vascular Smooth Muscle
Smooth Muscle Myocytes
Skin
Vascular Dementia
Antibodies
Genes
Mutation
Blood Vessels
Electron Microscopy
Arteries
Stroke
Electrons
Biopsy
Proteins

Keywords

  • CADASIL
  • Electron microscopy
  • Immunoelectron microscopy
  • Immunogold
  • Notch3

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Ishiko, A., Shimizu, A., Nagata, E., Takahashi, K., Tabira, T., & Suzuki, N. (2006). Notch3 ectodomain is a major component of granular osmiophilic material (GOM) in CADASIL. Acta Neuropathologica, 112(3), 333-339. https://doi.org/10.1007/s00401-006-0116-2

Notch3 ectodomain is a major component of granular osmiophilic material (GOM) in CADASIL. / Ishiko, Akira; Shimizu, Atsushi; Nagata, Eiichiro; Takahashi, Keikichi; Tabira, Takeshi; Suzuki, Norihiro.

In: Acta Neuropathologica, Vol. 112, No. 3, 09.2006, p. 333-339.

Research output: Contribution to journalArticle

Ishiko, A, Shimizu, A, Nagata, E, Takahashi, K, Tabira, T & Suzuki, N 2006, 'Notch3 ectodomain is a major component of granular osmiophilic material (GOM) in CADASIL', Acta Neuropathologica, vol. 112, no. 3, pp. 333-339. https://doi.org/10.1007/s00401-006-0116-2
Ishiko, Akira ; Shimizu, Atsushi ; Nagata, Eiichiro ; Takahashi, Keikichi ; Tabira, Takeshi ; Suzuki, Norihiro. / Notch3 ectodomain is a major component of granular osmiophilic material (GOM) in CADASIL. In: Acta Neuropathologica. 2006 ; Vol. 112, No. 3. pp. 333-339.
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