Skip to main content

Advertisement

SpringerLink
Log in

Discovering the Italian phenotype of cerebral amyloid angiopathy (CAA): the SENECA project

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

Cerebral amyloid angiopathy (CAA) is one of the major types of cerebral small vessel disease, and a leading cause of spontaneous intracerebral hemorrhage and cognitive decline in elderly patients. Although increasingly detected, a number of aspects including the pathophysiology, the clinical and neuroradiological phenotype, and the disease course are still under investigation. The incomplete knowledge of the disease limits the implementation of evidence-based guidelines on patient’s clinical management and the development of treatments able to prevent or reduce disease progression. The SENECA (SEarchiNg biomarkErs of Cerebral Angiopathy) project is the first Italian multicenter cohort study aimed at better defining the disease natural history and identifying clinical and neuroradiological markers of disease progression. By a multidisciplinary approach and the collection of a large and well-phenotyped series and biorepository of CAA patients, the study is ultimately expected to improve the diagnosis and the knowledge of CAA pathophysiological mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Banerjee G, Carare R, Cordonnier C, Greenberg SM, Schneider JA, Smith EE, Buchem MV, Grond JV, Verbeek MM, Werring DJ (2017) The increasing impact of cerebral amyloid angiopathy: essential new insights for clinical practice. J Neurol Neurosurg Psychiatry 88:982–994

    Article  Google Scholar 

  2. Charidimou A, Boulouis G, Gurol ME, Ayata C, Bacskai BJ, Frosch MP, Viswanathan A, Greenberg SM (2017) Emerging concepts in sporadic cerebral amyloid angiopathy. Brain 140:1829–1850

    Article  Google Scholar 

  3. Charidimou A, Gang Q, Werring DJ (2012) Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry 83:124–137

    Article  Google Scholar 

  4. Keable A, Fenna K, Yuen HM, Johnston DA, Smyth NR, Smith C, Al-Shahi Salman R, Samarasekera N, Nicoll JA, Attems J, Kalaria RN, Weller RO, Carare RO (2016) Deposition of amyloid β in the walls of human leptomeningeal arteries in relation to perivascular drainage pathways in cerebral amyloid angiopathy. Biochim Biophys Acta 1862:1037–1046

    Article  CAS  Google Scholar 

  5. Rostagno A, Holton JL, Lashley T, Revesz T, Ghiso J (2010) Cerebral amyloidosis: amyloid subunits, mutants and phenotypes. Cell Mol Life Sci 67:581–600

    Article  CAS  Google Scholar 

  6. Wermer MJH, Greenberg SM (2018) The growing clinical spectrum of cerebral amyloid angiopathy. Curr Opin Neurol 31:28–35

    Article  Google Scholar 

  7. Chen SJ, Tsai HH, Tsai LK, Tang SC, Lee BC, Liu HM, Yen RF, Jeng JS (2019) Advances in cerebral amyloid angiopathy imaging. Ther Adv Neurol Disord 12:1756286419844113

    PubMed  PubMed Central  Google Scholar 

  8. Sharma R, Dearaugo S, Infeld B, O'Sullivan R, Gerraty RP (2018) Cerebral amyloid angiopathy: Review of clinico-radiological features and mimics. J Med Imaging Radiat Oncol. https://doi.org/10.1111/1754-9485.12726

  9. Boulouis G, Charidimou A, Greenberg SM (2016) Sporadic cerebral amyloid angiopathy: pathophysiology, neuroimaging features, and clinical implications. Semin Neurol 36:233–243

    Article  Google Scholar 

  10. Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, Lindley RI, O'Brien JT, Barkhof F, Benavente OR, Black SE, Brayne C, Breteler M, Chabriat H, Decarli C, de Leeuw FE, Doubal F, Duering M, Fox NC, Greenberg S, Hachinski V, Kilimann I, Mok V, Rv O, Pantoni L, Speck O, Stephan BC, Teipel S, Viswanathan A, Werring D, Chen C, Smith C, van Buchem M, Norrving B, Gorelick PB, Dichgans M, STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1) (2013) Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 12:822–838

    Article  Google Scholar 

  11. Greenberg SM, Charidimou A (2018) Diagnosis of cerebral amyloid angiopathy: evolution of the Boston criteria. Stroke 49:491–497

    Article  Google Scholar 

  12. Rodrigues MA, Samarasekera N, Lerpiniere C, Humphreys C, McCarron MO, White PM, Nicoll JAR, Sudlow CLM, Cordonnier C, Wardlaw JM, Smith C, Al-Shahi Salman R (2018) The Edinburgh CT and genetic diagnostic criteria for lobar intracerebral haemorrhage associated with cerebral amyloid angiopathy: model development and diagnostic test accuracy study. Lancet Neurol 17:232–240

    Article  Google Scholar 

  13. Charidimou A, Farid K, Tsai HH, Tsai LK, Yen RF, Baron JC (2018) Amyloid-PET burden and regional distribution in cerebral amyloid angiopathy: a systematic review and meta-analysis of biomarker performance. J Neurol Neurosurg Psychiatry 89:410–417

    Article  Google Scholar 

  14. Charidimou A, Farid K, Baron JC (2017) Amyloid-PET in sporadic cerebral amyloid angiopathy: a diagnostic accuracy meta-analysis. Neurology 89:1490–1498

    Article  Google Scholar 

  15. Charidimou A, Friedrich JO, Greenberg SM, Viswanathan A (2018) Core cerebrospinal fluid biomarker profile in cerebral amyloid angiopathy: a meta-analysis. Neurology 90:e754–e762

    Article  CAS  Google Scholar 

  16. Charidimou A, Frosch MP, Salman RA, Baron JC, Cordonnier C, Hernandez-Guillamon M, Linn J, Raposo N, Rodrigues M, Romero JR, Schneider JA, Schreiber S, Smith EE, van Buchem MA, Viswanathan A, Wollenweber FA, Werring DJ, Greenberg SM, International CAA Association (2019) Advancing diagnostic criteria for sporadic cerebral amyloid angiopathy: atudy protocol for a multicenter MRI-pathology validation of Boston criteria v2.0. Int J Stroke 12:1747493019855888

    Google Scholar 

  17. Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H (2005) The Montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53:695–699

    Article  Google Scholar 

  18. Burton L, Tyson SF (2015) Screening for cognitive impairment after stroke: a systematic review of psychometric properties and clinical utility. J Rehabil Med 47(3):193–203. https://doi.org/10.2340/16501977-1930

    Article  PubMed  Google Scholar 

  19. Greenberg SM, Vernooij MW, Cordonnier C, Viswanathan A, Al-Shahi Salman R, Warach S, Launer LJ, Van Buchem MA, Breteler MM, Microbleed Study Group (2009) Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol 8:165–174

    Article  Google Scholar 

  20. Cordonnier C, Potter GM, Jackson CA, Doubal F, Keir S, Sudlow CL, Wardlaw JM, Al-Shahi Salman R (2009) Improving interrater agreement about brain microbleeds: development of the Brain Observer MicroBleed Scale (BOMBS). Stroke 40:94–99

    Article  Google Scholar 

  21. Gregoire SM, Chaudhary UJ, Brown MM, Yousry TA, Kallis C, Jäger HR, Werring DJ (2009) The Microbleed anatomical rating scale (MARS): reliability of a tool to map brain microbleeds. Neurology 73:1759–1766

    Article  CAS  Google Scholar 

  22. Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA (1987) MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. AJR Am J Roentgenol 149:351–356

    Article  CAS  Google Scholar 

  23. Charidimou A, Martinez-Ramirez S, Reijmer YD, Oliveira-Filho J, Lauer A, Roongpiboonsopit D, Frosch M, Vashkevich A, Ayres A, Rosand J, Gurol ME, Greenberg SM, Viswanathan A (2016) Total magnetic resonance imaging burden of small vessel disease in cerebral amyloid angiopathy: an imaging-pathologic study of concept validation. JAMA Neurol 73:994–1001

    Article  Google Scholar 

  24. Potter GM, Chappell FM, Morris Z, Wardlaw JM (2015) Cerebral perivascular spaces visible on magnetic resonance imaging: development of a qualitative rating scale and its observer reliability. Cerebrovasc Dis 39:224–231

    Article  Google Scholar 

  25. van Veluw SJ, Biessels GJ, Luijten PR, Zwanenburg JJ (2015) Assessing cortical cerebral microinfarcts on high resolution MR images. J Vis Exp 105 https://doi.org/10.3791/53125

  26. van Veluw SJ, Hilal S, Kuijf HJ, Ikram MK, Xin X, Yeow TB, Venketasubramanian N, Biessels GJ, Chen C (2015) Cortical microinfarcts on 3T MRI: clinical correlates in memory-clinic patients. Alzheimers Dement 11:1500–1509

    Article  Google Scholar 

  27. Pasquier F, Hamon M, Lebert F, Jacob B, Pruvo JP, Petit H (1997) Medial temporal lobe atrophy in memory disorders. J Neurol 244:175–181

    Article  CAS  Google Scholar 

  28. Song L, Xue R, Ge P, Li M, Wang L, Zheng F, Zhao L, Wang Z, Wang Z, Wang Q, Liu N, Sun X (2017) Identification of post-translational modifications of Aβ peptide in platelet membranes from patients with cerebral amyloid angiopathy. J Neurol Sci 383:11–17

    Article  CAS  Google Scholar 

  29. Kniewallner KM, Ehrlich D, Kiefer A, Marksteiner J, Humpel C (2015) Platelets in the Alzheimer's disease brain: do they play a role in cerebral amyloid angiopathy? Curr Neurovasc Res 12:4–14

    Article  CAS  Google Scholar 

  30. Howe MD, Atadja LA, Furr JW, Maniskas ME, Zhu L, McCullough LD, Urayama A (2018) Fibronectin induces the perivascular deposition of cerebrospinal fluid-derived amyloid-β in aging and after stroke. Neurobiol Aging 72:1–13

    Article  CAS  Google Scholar 

  31. Auriel E, Charidimou A, Gurol ME, Ni J, Van Etten ES, Martinez-Ramirez S, Boulouis G, Piazza F, DiFrancesco JC, Frosch MP, Pontes-Neto OV, Shoamanesh A, Reijmer Y, Vashkevich A, Ayres AM, Schwab KM, Viswanathan A, Greenberg SM (2016) Validation of Clinicoradiological criteria for the diagnosis of cerebral amyloid Angiopathy-related inflammation. JAMA Neurol 73:197–202

    Article  Google Scholar 

  32. Piazza F, Greenberg SM, Savoiardo M, Gardinetti M, Chiapparini L, Raicher I, Nitrini R, Sakaguchi H, Brioschi M, Billo G, Colombo A, Lanzani F, Piscosquito G, Carriero MR, Giaccone G, Tagliavini F, Ferrarese C, DiFrancesco JC (2013) Anti-amyloid β autoantibodies in cerebral amyloid angiopathy-related inflammation: implications for amyloid-modifying therapies. Ann Neurol 73:449–458

    Article  CAS  Google Scholar 

  33. Wollenweber FA, Opherk C, Zedde M, Catak C, Malik R, Duering M, Konieczny MJ, Pascarella R, Samões R, Correia M, Martí-Fàbregas J, Linn J, Dichgans M (2019) Prognostic relevance of cortical superficial siderosis in cerebral amyloid angiopathy. Neurology 92:e792–e801

    Article  CAS  Google Scholar 

  34. Gurol ME, Irizarry MC, Smith EE, Raju S, Diaz-Arrastia R, Bottiglieri T, Rosand J, Growdon JH, Greenberg SM (2006) Plasma beta-amyloid and white matter lesions in AD, MCI, and cerebral amyloid angiopathy. Neurology 66:23–29

    Article  CAS  Google Scholar 

  35. Weber SA, Patel RK, Lutsep HL (2018) Cerebral amyloid angiopathy: diagnosis and potential therapies. Expert Rev Neurother 18:503–513

    Article  CAS  Google Scholar 

  36. Charidimou A, Frosch MP, Salman RA, Baron JC, Cordonnier C, Hernandez-Guillamon M, Linn J, Raposo N, Rodrigues M, Romero JR, Schneider JA, Schreiber S, Smith EE, van Buchem MA, Viswanathan A, Wollenweber FA, Werring DJ, Greenberg SM; International CAA Association (2019) Advancing diagnostic criteria for sporadic cerebral amyloid angiopathy: study protocol for a multicenter MRI-pathology validation of Boston criteria v2.0. Int J Stroke 1747493019855888

  37. Leurent C, Goodman JA, Zhang Y, He P, Polimeni JR, Gurol ME, Lindsay M, Frattura L, Sohur US, Viswanathan A, Bednar MM, Smith EE, Ponezumab Trial Study Group, Greenberg SM (2019) Immunotherapy with ponezumab for probable cerebral amyloid angiopathy. Ann Clin Transl Neurol 6:795–806

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cerebrovascular Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

    Anna Bersano, Emma Scelzo & Eugenio A. Parati

  2. “Luigi Sacco” Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy

    Leonardo Pantoni

  3. Stroke Unit, IRCCS Foundation Neurological Institute C. Mondino, Pavia, Italy

    Andrea Morotti

  4. Neuroradiology Department, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

    Alessandra Erbetta & Luisa Chiapparini

  5. Neuroradiology Unit, Policlinico San Donato, Milan, Italy

    Paolo Vitali

  6. Unit of Neurology 5 and Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

    Giorgio Giaccone, Paola Caroppo, Marcella Catania & Giuseppe Di Fede

  7. Amyloidosis Research and Treatment Centre, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Laura Obici

  8. Neurobiology Laboratory, Cerebrovascular Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

    Laura Gatti & Francesca Tinelli

  9. Department of Neurology, Milan Center for Neuroscience, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy

    Jacopo C. Di Francesco & Carlo Ferrarese

  10. Milan Center for Neuroscience, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy

    Fabrizio Piazza

  11. Department of Nuclear Medicine, IRCCS MultiMedica Sesto San Giovanni, Milan, Italy

    Massimo Gasparini

  12. Stroke Unit, Istituto Auxologico Italiano IRCCS, Milan, Italy

    Laura Adobbati

  13. Neuro-ophthalmology Center and Electrophysiology Laboratory, Scientific Institute Capitanio Hospital, Istituto Auxologico Italiano IRCCS, Milan, Italy

    Stefania Bianchi-Marzoli & Gemma Tremolada

  14. Neuroscience Section, Department of Applied Clinical Science and Biotechnology, University of L’Aquila, L’Aquila, Italy

    Simona Sacco

  15. Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Pisa, Italy

    Michelangelo Mancuso

  16. Neurology Unit, Stroke Unit, Azienda Unità Sanitaria Locale – IRCCS di Reggio Emilia, Reggio Emilia, Italy

    Maria Luisa Zedde

  17. Department of Neurology, S. Andrea Hospital, La Spezia, Italy

    Massimiliano Godani

  18. Department of Neuroscience, Neurology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Silvia Lanfranconi

  19. Unit of Rare Neurodegenerative and Neurometabolic Diseases, Department of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

    Davide Pareyson

  20. Clinical Pathophysiology Center, AFaR Foundation, ‘San Giovanni Calibita’ Fatebenefratelli Hospital, Rome, Italy

    Marco Di Girolamo

  21. Stroke Unit, Niguarda Ca’ Granda Hospital, Milan, Italy

    Cristina Motto

  22. Hemorrhagic Stroke Research Program, J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Andreas Charidimou

  23. Neuroradiology Department, Paris Descartes University, INSERM U1266, DHU Neurovasculaire, Sainte-Anne Hospital, Paris, France

    Gregoire Boulouis

Authors
  1. Anna Bersano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emma Scelzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Leonardo Pantoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andrea Morotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alessandra Erbetta
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Luisa Chiapparini
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Paolo Vitali
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Giorgio Giaccone
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Paola Caroppo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Marcella Catania
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Laura Obici
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Giuseppe Di Fede
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Laura Gatti
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Francesca Tinelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Jacopo C. Di Francesco
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Fabrizio Piazza
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Carlo Ferrarese
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Massimo Gasparini
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Laura Adobbati
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Stefania Bianchi-Marzoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Gemma Tremolada
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Simona Sacco
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Michelangelo Mancuso
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Maria Luisa Zedde
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Massimiliano Godani
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Silvia Lanfranconi
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Davide Pareyson
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Marco Di Girolamo
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Cristina Motto
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. Andreas Charidimou
    View author publications

    You can also search for this author in PubMed Google Scholar

  31. Gregoire Boulouis
    View author publications

    You can also search for this author in PubMed Google Scholar

  32. Eugenio A. Parati
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of SENECA project

Corresponding author

Correspondence to Anna Bersano.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

None.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 16 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bersano, A., Scelzo, E., Pantoni, L. et al. Discovering the Italian phenotype of cerebral amyloid angiopathy (CAA): the SENECA project. Neurol Sci 41, 2193–2200 (2020). https://doi.org/10.1007/s10072-020-04306-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-020-04306-8

Keywords

Search

Navigation