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01-04-2021 | Dementia | Original Communication

SQSTM1 gene as a potential genetic modifier of CADASIL phenotype

Authors: Maria Rosário Almeida, Ana Rita Silva, Inês Elias, Carolina Fernandes, Rita Machado, Orlando Galego, Gustavo Cordeiro Santo

Published in: Journal of Neurology | Issue 4/2021

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common inherited cerebral small vessel disease and is caused by mutations in the NOTCH3 gene. Interestingly, CADASIL patients present a large phenotypic variability even harboring the same pathogenic variant. We describe two CADASIL siblings with a particularly aggressive clinical phenotype characterized by early-onset stroke, gait disturbances and/or dementia, severe emotional dysregulation, and dysexecutive syndrome together with a severe white matter burden on MRI. The genetic analysis revealed the co-occurrence of NOTCH3 (p.Gly420Cys) and SQSTM1 (p.Ser275Phefs*17) pathogenic variants which might worsen the aggressiveness of disease progression in both siblings. Interestingly, to the best of our knowledge, mutations in SQSTM1 gene have never been described in CADASIL patients before. Curiously, both Notch3 and p62 encoded proteins have a key role in the autophagy-lysosomal pathway which is impaired in CADASIL patients. Thus, the contribution of SQSTM1 gene to the clinical heterogeneity of CADASIL patients, in particular for those who develop cognitive impairment or dementia at an early age, is certainly overlooked. Therefore, we advocate expanding the genetic analysis to other genes associated with the phenotype spectrum of CADASIL patients using NGS-customized gene panel.

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Opherk C, Peters N, Herzog J, Luedtke R, Dichgans M (2004) Long- term prognosis and causes of death in CADASIL: a retrospective study in 411 patients. Brain 127(Pt 11):2533–2539. https://doi.org/10.1093/brain/awh282CrossRefPubMed

Chabriat H, Vahedi K, Bousser MG, Iba-Zizen MT, Joutel A, Nibbio A, Nagy TG, Tournier Lasserve E, Krebs MO, Julien J, Ducrocq X, Levasseur M, Mas JL, Dubois B, Homeyer P, Lyon-Caen O (1995) Clinical spectrum of CADASIL: a study of 7 families. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Lancet 346(8980):934–939. https://doi.org/10.1016/s0140-6736(95)91557-5CrossRefPubMed

Kalimo H, Viitanen M, Amberla K, Juvonen V, Marttila R, Pöyhönen M, Rinne JO, Savontaus M, Tuisku S, Winblad B (1999) CADASIL: hereditary disease of arteries causing brain infarcts and dementia. Neuropathol Appl Neurobiol 25(4):257–265. https://doi.org/10.1046/j.1365-2990.1999.00198.xCrossRefPubMed

Di Donato I, Bianchi S, De Stefano N, Dichgans M, Dotti MT, Duering M, Jouvent E, Korczyn AD, Lesnik-Oberstein SA, Malandrini A, Markus HS, Pantoni L, Penco S, Rufa A, Sinanović O, Stojanov D, Federico A (2017) Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) as a model of small vessel disease: update on clinical, diagnostic, and management aspects. BMC Med 15(1):41. https://doi.org/10.1186/s12916-017-0778-8CrossRefPubMedPubMedCentral

Dichgans M, Mayer M, Uttner I, Brüning R, Müller-Höcker J, Rungger G, Ebke M, Klockgether T, Gasser T (1998) The phenotypic spectrum of CADASIL: clinical findings in 102 cases. Ann Neurol 44(5):731–739. https://doi.org/10.1002/ana.410440506CrossRefPubMed

Noh SM, Chung SJ, Kim KK et al (2014) Emotional disturbance in CADASIL: its impact on quality of life and caregiver burden. Cerebrovasc Dis 37(3):188–194. https://doi.org/10.1159/000357798CrossRefPubMed

Joutel A, Monet-Leprêtre M, Gosele C, Baron-Menguy C, Hammes A, Schmidt S, Lemaire-Carrette B, Domenga V, Schedl A, Lacombe P, Hubner N (2010) Cerebrovascular dysfunction and microcirculation rarefaction precede white matter lesions in a mouse genetic model of cerebral ischemic small vessel disease. J Clin Invest 120(2):433–445. https://doi.org/10.1172/JCI39733CrossRefPubMedPubMedCentral

Joutel A, Andreux F, Gaulis S, Domenga V, Cecillon M, Battail N, Piga N, Chapon F, Godfrain C, Tournier-Lasserve E (2000) The ectodomain of the Notch3 receptor accumulates within the cerebrovasculature of CADASIL patients. J Clin Invest 105(5):597–605. https://doi.org/10.1172/JCI8047CrossRefPubMedPubMedCentral

Tournier-Lasserve E, Joutel A, Melki J, Weissenbach J, Lathrop GM, Chabriat H, Mas JL, Cabanis EA, Baudrimont M, Maciazek J et al (1993) Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy maps to chromosome 19q12. Nat Genet 3(3):256–259. https://doi.org/10.1038/ng0393-256CrossRefPubMed

10.

Joutel A, Corpechot C, Ducros A, Vahedi K, Chabriat H, Mouton P, Alamowitch S, Domenga V, Cécillion M, Marechal E, Maciazek J, Vayssiere C, Cruaud C, Cabanis EA, Ruchoux MM, Weissenbach J, Bach JF, Bousser MG, Tournier-Lasserve E (1996) Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 383(6602):707–710. https://doi.org/10.1038/383707a0CrossRefPubMed

11.

Wang T, Baron M, Trump D (2008) An overview of Notch3 function in vascular smooth muscle cells. Prog Biophys Mol Biol 96(1–3):499–509. https://doi.org/10.1016/j.pbiomolbio.2007.07.006CrossRefPubMed

12.

Siebel C, Lendahl U (2017) Notch signaling in development, tissue homeostasis, and disease. Physiol Rev 97(4):1235–1294. https://doi.org/10.1152/physrev.00005.2017CrossRefPubMed

13.

Coupland K, Lendahl U, Karlström H (2018) Role of NOTCH3 mutations in the cerebral small vessel disease cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke 49(11):2793–2800. https://doi.org/10.1161/STROKEAHA.118.021560CrossRefPubMed

14.

Boucher J, Gridley T, Liaw L (2012) Molecular pathways of notch signaling in vascular smooth muscle cells. Front Physiol 9(3):81. https://doi.org/10.3389/fphys.2012.00081CrossRef

15.

Dunn PJ, Maksemous N, Smith RA, Sutherland HG, Haupt LM, Griffiths LR (2020) Investigating diagnostic sequencing techniques for CADASIL diagnosis. Hum Genomics 14(1):2. https://doi.org/10.1186/s40246-019-0255-xCrossRefPubMedPubMedCentral

16.

Joutel A, Vahedi K, Corpechot C, Troesch A, Chabriat H, Vayssière C, Cruaud C, Maciazek J, Weissenbach J, Bousser MG, Bach JF, Tournier-Lasserve E (1997) Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients. Lancet 350(9090):1511–1515. https://doi.org/10.1016/S0140-6736(97)08083-5CrossRefPubMed

17.

Rutten JW, Dauwerse HG, Gravesteijn G, van Belzen MJ, van der Grond J, Polke JM, Bernal-Quiros M, Lesnik Oberstein SA (2016) Archetypal <i>NOTCH3</i> mutations frequent in public exome: implications for CADASIL. Ann Clin Transl Neurol 3(11):844–853. https://doi.org/10.1002/acn3.344CrossRefPubMedPubMedCentral

18.

Duering M, Karpinska A, Rosner S, Hopfner F, Zechmeister M, Peters N, Kremmer E, Haffner C, Giese A, Dichgans M, Opherk C (2011) Co-aggregate formation of CADASIL- mutant NOTCH3: a single-particle analysis. Hum Mol Genet 20(16):3256–3265. https://doi.org/10.1093/hmg/ddr237CrossRefPubMed

19.

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 Neuropathol 112(3):333–339. https://doi.org/10.1007/s00401-006-0116-2CrossRefPubMed

20.

Tikka S, Mykkänen K, Ruchoux MM, Bergholm R, Junna M, Pöyhönen M, Yki- Järvinen H, Joutel A, Viitanen M, Baumann M, Kalimo H (2009) Congruence between NOTCH3 mutations and GOM in 131 CADASIL patients. Brain 132(Pt 4):933–939. https://doi.org/10.1093/brain/awn364CrossRefPubMedPubMedCentral

21.

Okeda R, Arima K, Kawai M (2002) Arterial changes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in relation to pathogenesis of diffuse myelin loss of cerebral white matter: examination of cerebral medullary arteries by reconstruction of serial sections of an autopsy case. Stroke 33(11):2565–2569. https://doi.org/10.1161/01.str.0000032620.91848.1cCrossRefPubMed

22.

Yamamoto Y, Ihara M, Tham C, Low RW, Slade JY, Moss T, Oakley AE, Polvikoski T, Kalaria RN (2009) Neuropathological correlates of temporal pole white matter hyperintensities in CADASIL. Stroke 40(6):2004–2011. https://doi.org/10.1161/STROKEAHA.108.528299CrossRefPubMedPubMedCentral

23.

Miao Q, Paloneva T, Tuominen S, Pöyhönen M, Tuisku S, Viitanen M, Kalimo H (2004) Fibrosis and stenosis of the long penetrating cerebral arteries: the cause of the white matter pathology in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Brain Pathol 14(4):358–364. https://doi.org/10.1111/j.1750-3639.2004.tb00078.xCrossRefPubMed

24.

Yao M, Hervé D, Jouvent E, Duering M, Reyes S, Godin O, Guichard JP, Dichgans M, Chabriat H (2014) Dilated perivascular spaces in small-vessel disease: a study in CADASIL. Cerebrovasc Dis 37(3):155–163. https://doi.org/10.1159/000356982CrossRefPubMed

25.

Ruchoux MM, Chabriat H, Bousser MG, Baudrimont M, Tournier-Lasserve E (1994) Presence of ultrastructural arterial lesions in muscle and skin vessels of patients with CADASIL. Stroke 25(11):2291–2292. https://doi.org/10.1161/01.str.25.11.2291CrossRefPubMed

26.

Mancuso M, Arnold M, Bersano A et al (2020) Monogenic cerebral small-vessel diseases: diagnosis and therapy. Consensus recommendations of the European Academy of Neurology. Eur J Neurol 27(6):909–927. https://doi.org/10.1111/ene.14183CrossRefPubMed

27.

Joutel A, Favrole P, Labauge P, Chabriat H, Lescoat C, Andreux F, Domenga V, Cécillon M, Vahedi K, Ducros A, Cave-Riant F, Bousser MG, Tournier-Lasserve E (2001) Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis. Lancet 358(9298):2049–2051. https://doi.org/10.1016/S0140-6736(01)07142-2CrossRefPubMed

28.

Kalimo H, Ruchoux MM, Viitanen M, Kalaria RN (2002) CADASIL: a common form of hereditary arteriopathy causing brain infarcts and dementia. Brain Pathol 12(3):371–384. https://doi.org/10.1111/j.1750-3639.2002.tb00451.xCrossRefPubMed

29.

Sathe S, DePeralta E, Pastores G, Kolodny EH (2009) Acute confusional migraine may be a presenting feature of CADASIL. Headache 49(4):590–596. https://doi.org/10.1111/j.1526-4610.2009.01363.xCrossRefPubMed

30.

Mehta S, Mehndiratta P, Sila CA (2013) Spontaneous cerebellar hemorrhage associated with a novel Notch3 mutation. J Clin Neurosci 20(7):1034–1036. https://doi.org/10.1016/j.jocn.2012.11.003CrossRefPubMed

31.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, ACMG Laboratory Quality Assurance Committee (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17(5):405–424. https://doi.org/10.1038/gim.2015.30CrossRefPubMedPubMedCentral

32.

Kumar P, Henikoff S, Ng PC (2009) Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 4(7):1073–1081. https://doi.org/10.1038/nprot.2009.86CrossRefPubMed

33.

Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR (2010) A method and server for predicting damaging missense mutations. Nat Methods 7(4):248–249. https://doi.org/10.1038/nmeth0410-248CrossRefPubMedPubMedCentral

34.

Schwarz JM, Rödelsperger C, Schuelke M, Seelow D (2010) MutationTaster evaluates disease-causing potential of sequence alterations. Nat Methods 7(8):575–576. https://doi.org/10.1038/nmeth0810-575CrossRefPubMed

35.

Pejaver V, Urresti J, Lugo-Martinez J, Pagel KA, Lin GN, Nam H, Mort M, Cooper DN, Sebat J, Iakoucheva LM, Mooney SD, Radivojac P (2017) MutPred2: inferring the molecular and phenotypic impact of amino acid variants. bioRxiv 134981; doi: https://doi.org/10.1101/134981

36.

Rentzsch P, Witten D, Cooper GM, Shendure J, Kircher M (2019) CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res 47(D1):D886–D894. https://doi.org/10.1093/nar/gky1016CrossRefPubMed

37.

Guerreiro M, Silva AP, Botelho MA, Leitão O, Castro-Caldas A, Garcia C (1994) Adaptação à população portuguesa da tradução do Mini Mental State Examination (MMSE) [Adaptation to the Portuguese population of the translation of the Mini Mental State Examination]. Revista Portuguesa de Neurologia 1(9):9–10

38.

Freitas S, Simões MR, Alves L, Santana I (2011) Montreal Cognitive Assessment (MoCA): normative study for the Portuguese population. J Clin Exp Neuropsychol 33:989–996. https://doi.org/10.1080/13803395.2011.589374CrossRefPubMed

39.

Lemos R, Martins C, Simões MR, Santana I (2012) Estudo de adaptação do Teste de Recordação Selectiva Livre e Guiada para a população portuguesa [Adaptation study of the Free and Cued Selective Reminding Test for the Portuguese population]. Avaliação Psicológica 11(1):49–61

40.

Fernandes S (2013) Stroop—Teste de Cores e Palavras [Stroop—colors and wording test]. Cegoc, Lisboa

41.

Espirito-Santo H, Lemos L, Torres-Pena I, Vicente F, Silva F, Costa M, Marques M, Simões S, Guadalupe S, e Daniel FB (2015) Bateria de avaliação frontal (FAB). EM Simões, I Santana e Grupo de Estudos de Envelhecimento Cerebral e Demência (coord.). 3rd Eds. Escalas e testes na demência. Novartis, Porto Salvo. pp. 68–75

42.

Freitas S, Nogueira J, Gerardo B, Simões MR (2018) Protocolo de Fluência Verbal (PFV) [The verbal fluency protocol (VFP)]. Coimbra, Portugal: PsyLabAssessment, Faculdade de Psicologia e de Ciências da Educação da Universidade de Coimbra

43.

Wechsler D (2008) Escala de Inteligência de Wechsler para Adultos—Terceira edição (WAIS-III) [Wechsler Adult Intelligence Scale-Third Edition]. Cegoc, Lisboa

44.

Pestana J, Menéres S, Gouveia M, Oliveira R (2018) The reading the mind in the eyes test: a Portuguese version of the adults test. Análise Psicológica 36(3):369–381. https://doi.org/10.14417/ap.1305CrossRef

45.

Pais-Ribeiro J, Silva I, Ferreira T, Martins A, Meneses R, Baltar M (2007) Validation study of a Portuguese version of the Hospital Anxiety and Depression Scale. Psychol Health Med 12(2):225–237CrossRefPubMed

46.

Coutlee CG, Politzer CS, Hoyle RH, Huettel SA (2014) An abbreviated impulsiveness scale constructed through confirm- atory factor analysis of the Barratt impulsiveness scale version 11. Arch Sci Psychol 2(1):1PubMedPubMedCentral

47.

Simões MR, Sousa LB, Vilar M, Pinho MS, Prieto G, Firmino H (2017) Escala de Depressão Geriátrica (GDS) [Geriatric Depression Scale]. In: MM Gonçalves, MR Simões, LS Almeida (Coord.). Psicologia Clínica e da Saúde [Clinical Psychology and Health]. Lisboa: PACTOR. pp.219–233. ISBN 978–989–693–064–6

48.

Zúñiga-Ramírez C, de Oliveira LM, Kramis-Hollands M, Algarni M, Soto-Escageda A, Sáenz-Farret M, González-Usigli HA, Fasano A (2019) Beyond dystonia and ataxia: expanding the phenotype of SQSTM1 mutations. Parkinsonism Relat Disord 62:192–195. https://doi.org/10.1016/j.parkreldis.2018.12.031CrossRefPubMed

49.

Rutten JW, Haan J, Terwindt GM, van Duinen SG, Boon EM, Lesnik Oberstein SA (2014) Interpretation of NOTCH3 mutations in the diagnosis of CADASIL. Expert Rev Mol Diagn 14(5):593–603. https://doi.org/10.1586/14737159.2014.922880CrossRefPubMed

50.

Rutten JW, Van Eijsden BJ, Duering M, Jouvent E, Opherk C, Pantoni L, Federico A, Dichgans M, Markus HS, Chabriat H, Lesnik Oberstein SAJ (2019) The effect of NOTCH3 pathogenic variant position on CADASIL disease severity: NOTCH3 EGFr 1–6 pathogenic variant are associated with a more severe phenotype and lower survival compared with EGFr 7–34 pathogenic variant. Genet Med 21(3):676–682. https://doi.org/10.1038/s41436-018-0088-3CrossRefPubMed

51.

Bjørkøy G, Lamark T, Johansen T (2006) p62/SQSTM1: a missing link between protein aggregates and the autophagy machinery. Autophagy 2(2):138–139. https://doi.org/10.4161/auto.2.2.2405CrossRefPubMed

52.

Wooten MW, Geetha T, Babu JR, Seibenhener ML, Peng J, Cox N, Diaz-Meco MT, Moscat J (2008) Essential role of sequestosome 1/p62 in regulating accumulation of Lys63-ubiquitinated proteins. J Biol Chem 283(11):6783–6789. https://doi.org/10.1074/jbc.M709496200CrossRefPubMed

53.

Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, Øvervatn A, Bjørkøy G, Johansen T (2007) p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 282(33):24131–24145. https://doi.org/10.1074/jbc.M702824200CrossRefPubMed

54.

Hewitt G, Korolchuk VI (2017) Repair, reuse, recycle: the expanding role of autophagy in genome maintenance. Trends Cell Biol 27(5):340–351. https://doi.org/10.1016/j.tcb.2016.11.011CrossRefPubMed

55.

Seibenhener ML, Babu JR, Geetha T, Wong HC, Krishna NR, Wooten MW (2004) Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation. Mol Cell Biol 24(18):8055–8068. https://doi.org/10.1128/MCB.24.18.8055-8068.2004CrossRefPubMedPubMedCentral

56.

Babu JR, Geetha T, Wooten MW (2005) Sequestosome 1/p62 shuttles polyubiquitinated tau for proteasomal degradation. J Neurochem 94(1):192–203. https://doi.org/10.1111/j.1471-4159.2005.03181.xCrossRefPubMed

57.

Laurin N, Brown JP, Morissette J, Raymond V (2002) Recurrent mutation of the gene encoding sequestosome 1 (SQSTM1/p62) in Paget disease of bone. Am J Hum Genet 70(6):1582–1588. https://doi.org/10.1086/340731CrossRefPubMedPubMedCentral

58.

Le Ber I, Camuzat A, Guerreiro R, Bouya-Ahmed K, Bras J, Nicolas G, Gabelle A, Didic M, De Septenville A, Millecamps S, Lenglet T, Latouche M, Kabashi E, Campion D, Hannequin D, Hardy J, Brice A (2013) French Clinical and Genetic Research Network on FTD/FTD-ALS SQSTM1 mutations in French patients with frontotemporal dementia or frontotemporal dementia with amyotrophic lateral sclerosis. JAMA Neurol 70(11):1403–1410. https://doi.org/10.1001/jamaneurol.2013.3849CrossRefPubMedPubMedCentral

59.

Rubino E, Rainero I, Chiò A, Rogaeva E, Galimberti D, Fenoglio P, Grinberg Y, Isaia G, Calvo A, Gentile S, Bruni AC, St George-Hyslop PH, Scarpini E, Gallone S, Pinessi L, TODEM Study Group (2012) SQSTM1 mutations in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Neurology 79(15):1556–1562. https://doi.org/10.1212/WNL.0b013e31826e25dfCrossRefPubMedPubMedCentral

60.

Kuusisto E, Salminen A, Alafuzoff I (2002) Early accumulation of p62 in neurofibrillary tangles in Alzheimer’s disease: possible role in tangle formation. Neuropathol Appl Neurobiol 28(3):228–237. https://doi.org/10.1046/j.1365-2990.2002.00394.xCrossRefPubMed

61.

Nakaso K, Yoshimoto Y, Nakano T, Takeshima T, Fukuhara Y, Yasui K, Araga S, Yanagawa T, Ishii T, Nakashima K (2004) Transcriptional activation of p62/A170/ZIP during the formation of the aggregates: possible mechanisms and the role in Lewy body formation in Parkinson’s disease. Brain Res 1012(1–2):42–51. https://doi.org/10.1016/j.brainres.2004.03.029CrossRefPubMed

62.

Ma S, Attarwala IY, Xie XQ (2019) SQSTM1/p62: a potential target for neurodegenerative disease. ACS Chem Neurosci 10(5):2094–2114. https://doi.org/10.1021/acschemneuro.8b00516CrossRefPubMed

63.

Geetha T, Wooten MW (2002) Structure and functional properties of the ubiquitin binding protein p62. FEBS Lett 512(1–3):19–24. https://doi.org/10.1016/s0014-5793(02)02286-xCrossRefPubMed

64.

Hase Y, Chen A, Bates LL, Craggs LJL, Yamamoto Y, Gemmell E, Oakley AE, Korolchuk VI, Kalaria RN (2018) Severe white matter astrocytopathy in CADASIL. Brain Pathol 28(6):832–843. https://doi.org/10.1111/bpa.12621CrossRefPubMedPubMedCentral

65.

Hanemaaijer ES, Panahi M, Swaddiwudhipong N, Tikka S, Winblad B, Viitanen M, Piras A, Behbahani H (2018) Autophagy-lysosomal defect in human CADASIL vascular smooth muscle cells. Eur J Cell Biol 97(8):557–567. https://doi.org/10.1016/j.ejcb.2018.10.001CrossRefPubMed

66.

Rami A, Langhagen A, Steiger S (2008) Focal cerebral ischemia induces upregulation of Beclin 1 and autophagy-like cell death. Neurobiol Dis 29(1):132–141. https://doi.org/10.1016/j.nbd.2007.08.005CrossRefPubMed

67.

Xu F, Gu JH, Qin ZH (2012) Neuronal autophagy in cerebral ischemia. Neurosci Bull 28(5):658–666. https://doi.org/10.1007/s12264-012-1268-9CrossRefPubMedPubMedCentral

68.

Puissant A, Fenouille N, Auberger P (2012) When autophagy meets cancer through p62/SQSTM1. Am J Cancer Res 28(6):832–843. https://doi.org/10.1111/bpa.12621CrossRef

69.

Risacher SL, Saykin AJ, West JD et al (2009) Baseline MRI predictors of conversion from MCI to probable AD in the ADNI cohort. Curr Alzheimer Res 6(4):347–361. https://doi.org/10.2174/156720509788929273CrossRefPubMedPubMedCentral

70.

Gesierich B, Opherk C, Rosand J, Gonik M, Malik R, Jouvent E, Hervé D, Adib-Samii P, Bevan S, Pianese L, Silvestri S, Dotti MT, De Stefano N, van der Grond J, Boon EM, Pescini F, Rost N, Pantoni L, Oberstein SA, Federico A, Ragno M, Markus HS, Tournier-Lasserve E, Chabriat H, Dichgans M, Duering M, Ewers M (2016) APOE ɛ2 is associated with white matter hyperintensity volume in CADASIL. J Cereb Blood Flow Metab 36(1):199–203. https://doi.org/10.1038/jcbfm.2015.85CrossRefPubMedPubMedCentral

71.

Viswanathan A, Gschwendtner A, Guichard JP, Buffon F, Cumurciuc R, O’Sullivan M, Holtmannspötter M, Pachai C, Bousser MG, Dichgans M, Chabriat H (2007) Lacunar lesions are independently associated with disability and cognitive impairment in CADASIL. Neurology 69(2):172–179. https://doi.org/10.1212/01.wnl.0000265221.05610.70CrossRefPubMed

72.

Liem MK, van der Grond J, Haan J, van den Boom R, Ferrari MD, Knaap YM, Breuning MH, van Buchem MA, Middelkoop HA, Lesnik Oberstein SA (2007) Lacunar infarcts are the main correlate with cognitive dysfunction in CADASIL. Stroke 38(3):923–928. https://doi.org/10.1161/01.STR.0000257968.24015.bfCrossRefPubMed

Title: SQSTM1 gene as a potential genetic modifier of CADASIL phenotype
Authors: Maria Rosário Almeida
Ana Rita Silva
Inês Elias
Carolina Fernandes
Rita Machado
Orlando Galego
Gustavo Cordeiro Santo
Publication date: 01-04-2021
Publisher: Springer Berlin Heidelberg
Keywords: Dementia
Dementia
CADASIL
Published in: Journal of Neurology / Issue 4/2021
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-020-10308-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

SQSTM1 gene as a potential genetic modifier of CADASIL phenotype

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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