Neuropathology of SCA34 showing widespread oligodendroglial pathology with vacuolar white matter degeneration: a case study.

Publisher: BioMed Central Country of Publication: England NLM ID: 101610673 Publication Model: Electronic Cited Medium: Internet ISSN: 2051-5960 (Electronic) Linking ISSN: 20515960 NLM ISO Abbreviation: Acta Neuropathol Commun Subsets: MEDLINE

Original Publication: London : BioMed Central, [2013]-

Brain/*pathology ; Nerve Degeneration/*pathology ; Oligodendroglia/*pathology ; Spinocerebellar Ataxias/*pathology ; White Matter/*pathology; Aged, 80 and over ; Eye Proteins/genetics ; Humans ; Male ; Membrane Proteins/genetics ; Mutation, Missense ; Nerve Degeneration/genetics ; Spinocerebellar Ataxias/genetics ; Vacuoles/pathology

Spinocerebellar ataxia type 34 (SCA34) is an autosomal dominant inherited ataxia due to mutations in ELOVL4, which encodes one of the very long-chain fatty acid elongases. SCA38, another spinocerebellar ataxia, is caused by mutations in ELOVL5, a gene encoding another elongase. However, there have been no previous studies describing the neuropathology of either SCA34 or 38. This report describes the neuropathological findings of an 83-year-old man with SCA34 carrying a pathological ELOVL4 mutation (NM_022726, c.736T>G, p.W246G). Macroscopic findings include atrophies in the pontine base, cerebellum, and cerebral cortices. Microscopically, marked neuronal and pontocerebellar fiber loss was observed in the pontine base. In addition, in the pontine base, accumulation of CD68-positive macrophages laden with periodic acid-Schiff (PAS)-positive material was observed. Many vacuolar lesions were found in the white matter of the cerebral hemispheres and, to a lesser extent, in the brainstem and spinal cord white matter. Immunohistological examination and ultrastructural observations with an electron microscope suggest that these vacuolar lesions are remnants of degenerated oligodendrocytes. Electron microscopy also revealed myelin sheath destruction. Unexpectedly, aggregation of the four-repeat tau was observed in a spatial pattern reminiscent of progressive supranuclear palsy. The tau lesions included glial fibrillary tangles resembling tuft-shaped astrocytes and neurofibrillary tangles and pretangles. This is the first report to illustrate that a heterozygous missense mutation in ELOVL4 leads to neuronal loss accompanied by macrophages laden with PAS-positive material in the pontine base and oligodendroglial degeneration leading to widespread vacuoles in the white matter in SCA34.
(© 2021. The Author(s).)

BMC Neurol. 2020 Apr 15;20(1):136. (PMID: 32293309)
Neuropathol Appl Neurobiol. 2014 Feb;40(2):225-30. (PMID: 23692129)
JAMA Neurol. 2015 Jul;72(7):797-805. (PMID: 26010696)
Arch Dermatol. 1972 Aug;106(2):183-8. (PMID: 5048218)
Neuropathology. 2016 Feb;36(1):64-76. (PMID: 26227820)
Front Cell Neurosci. 2019 Sep 20;13:428. (PMID: 31616255)
Acta Neuropathol. 2017 May;133(5):809-823. (PMID: 28064358)
Neurol Genet. 2020 Feb 20;6(2):e403. (PMID: 32211516)
Neuron. 2004 Nov 18;44(4):601-7. (PMID: 15541309)
Parkinsonism Relat Disord. 2019 Aug;65:238-242. (PMID: 31105016)
Neurol Genet. 2019 Sep 23;5(5):e357. (PMID: 31750392)
Acta Neuropathol. 2014 Dec;128(6):755-66. (PMID: 25348064)
Mol Neurobiol. 2021 Oct;58(10):4921-4943. (PMID: 34227061)
J Biol Chem. 2011 Aug 26;286(34):30022-33. (PMID: 21705317)
Brain. 2018 Aug 1;141(8):2329-2342. (PMID: 29860501)
J Lipid Res. 2010 Jul;51(7):1624-42. (PMID: 20299492)
Parkinsonism Relat Disord. 2016 Jul;28:80-6. (PMID: 27143115)
Front Neuroanat. 2017 May 01;11:38. (PMID: 28507511)
Acta Neuropathol Commun. 2014 Feb 07;2:15. (PMID: 24502382)
Acta Neuropathol. 1990;80(5):541-6. (PMID: 2251912)
Parkinsonism Relat Disord. 2011 Jun;17(5):365-71. (PMID: 21420891)
Acta Neuropathol. 2007 May;113(5):483-99. (PMID: 17401570)
Nat Genet. 2001 Jan;27(1):89-93. (PMID: 11138005)
Am J Hum Genet. 2011 Dec 9;89(6):745-50. (PMID: 22100072)
Neurol Genet. 2018 Jul 26;4(4):e263. (PMID: 30065956)
Am J Hum Genet. 2014 Aug 7;95(2):209-17. (PMID: 25065913)
Annu Rev Pathol. 2012;7:185-217. (PMID: 22313379)
J Neurol Neurosurg Psychiatry. 1996 Jun;60(6):615-20. (PMID: 8648326)
J Biochem. 2012 Nov;152(5):387-95. (PMID: 22984005)
Brain Pathol. 2005 Oct;15(4):287-95. (PMID: 16389941)
Neurology. 2018 Nov 20;91(21):e1988-e1998. (PMID: 30381368)
Acta Neuropathol. 2006 Oct;112(4):389-404. (PMID: 16906426)
Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18439-44. (PMID: 20937905)
Rinsho Shinkeigaku. 2012;52(3):156-60. (PMID: 22453039)
Acta Neuropathol. 2005 Feb;109(2):159-64. (PMID: 15549333)
Folia Neuropathol. 2016;54(1):9-22. (PMID: 27179217)
Sci Rep. 2019 Sep 13;9(1):13213. (PMID: 31519997)
PLoS One. 2011 Jan 11;6(1):e15946. (PMID: 21264320)
Neuropathology. 2011 Oct;31(5):510-8. (PMID: 21134000)
Sci Rep. 2018 Oct 12;8(1):15207. (PMID: 30315256)
JAMA Neurol. 2015 Aug;72(8):942-3. (PMID: 26258735)
JAMA Neurol. 2014 Apr;71(4):470-5. (PMID: 24566826)
Mol Neurobiol. 2020 Nov;57(11):4735-4753. (PMID: 32780351)
Neurodegener Dis. 2016;16(1-2):12-21. (PMID: 26550830)
Mol Neurobiol. 2018 Feb;55(2):1795-1813. (PMID: 29168048)
J Neurol Sci. 2018 Apr 15;387:187-195. (PMID: 29571861)
J Alzheimers Dis. 2002 Oct;4(5):399-404. (PMID: 12446971)
J Biol Chem. 2009 Nov 27;284(48):33549-60. (PMID: 19801672)

Keywords: Fatty acid elongase; Four-repeat tau; Neuropathology; Progressive supranuclear palsy (PSP); Spinocerebellar ataxia type 34 (SCA34); Tauopathy; Tuft shaped astrocytes; Very long-chain fatty acids (VLCFA)

0 (ELOVL4 protein, human)
0 (Eye Proteins)
0 (Membrane Proteins)

Date Created: 20211025 Date Completed: 20220221 Latest Revision: 20220221

20240829

PMC8543940

10.1186/s40478-021-01272-w

34689836