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BIOmarkers for cogNitive Impairment due to Cerebral Amyloid Angiopathy (BIONIC)

Projectomschrijving

Samenklontering van het eiwit amyloïd-bèta in de bloedvaten van de hersenen wordt Cerebrale Amyloïd Angiopathie (CAA) genoemd. Dit kan leiden tot bloedingen en vermindering van verstandelijke vermogens. 

Doel BIONIC

Het doel van het BIONIC onderzoek was om nieuwe biomarkers te vinden voor CAA en de diagnostische waarde hiervan te onderzoeken in groepen patiënten. 

Aanpak

Deelnemers werd gevraagd hersenvocht en bloed af te staan en een MRI en neuropsychologische testen te ondergaan. 

Resultaten BIONIC

In dit BIONIC onderzoek vonden we: (1) dat een panel van amyloïd-bèta, en andere, eiwitten specifieke biomarkers zijn voor CAA, zelfs in vroege stadia van de aandoening, en dat deze correleerden met de mate van verstandelijke vermogens; (2) biomarkers die nieuwe inzichten geven in het ontstaan van deze aandoening. 

De nieuwe biomarkers hebben potentiële toepassingen in de toekomst: (1) betere en vroegtijdigere diagnostiek van CAA; (2) het selecteren van (Alzheimer) patiënten voor anti-amyloïd-bèta immunotherapie; voor sommige patiënten is het namelijk, vanwege de grote mate van CAA in hun hersenen, mogelijk veiliger om geen immunotherapie te ondergaan, omdat dit leidt tot schadelijke bijwerkingen.

Meer informatie

BIONIC website Radboudumc

Producten

Titel: Validation of the LUMIPULSE automated immunoassay for the measurement of core AD biomarkers in cerebrospinal fluid.
Auteur: Gobom J, Parnetti L, Rosa-Neto P, Vyhnalek M, Gauthier S, Cataldi S, Lerch O, Laczo J, Cechova K, Clarin M, Benet AL, Pascoal TA, Rahmouni N, Vandijck M, Huyck E, Le Bastard N, Stevenson J, Chamoun M, Alcolea D, Lleó A, Andreasson U, Verbeek MM, Bellomo G, Rinaldi R, Ashton NJ, Zetterberg H, Sheardova K, Hort J, Blennow K
Magazine: Clinical Chemistry and Laboratory Medicine
Titel: Decreased ratios of matrix metalloproteinases to tissue-type inhibitors in cerebrospinal fluid in sporadic and hereditary cerebral amyloid angiopathy
Auteur: Vervuurt M, de Kort AM, Jäkel L, Kersten I, Abdo WF, Schreuder FHBM, Rasing I, Terwindt GM, Wermer MJH, Greenberg SM, Klijn CJM, Kuiperij HB, Verbeek MM.
Magazine: Neuropathol Appl Neurobiol.
Begin- en eindpagina:
Titel: Antisense Oligonucleotide-Induced Amyloid Precursor Protein Splicing Modulation as a Therapeutic Approach for Dutch-Type Cerebral Amyloid Angiopathy
Auteur: Daoutsali E, Hailu TT, Buijsen RAM, Pepers BA, van der Graaf LM, Verbeek MM, Curtis D, de Vlaam T, van Roon-Mom WMC.
Magazine: Nucleic Acid Ther
Begin- en eindpagina:
Titel: Plasma amyloid beta 42 is a biomarker for patients with hereditary, but not sporadic, cerebral amyloid angiopathy
Auteur: de Kort AM, Kuiperij HB, Jäkel L, Kersten I, Rasing I, van Etten ES, van Rooden S, van Osch MJP, Wermer MJH, Terwindt GM, Schreuder FHBM, Klijn CJM, Verbeek MM.
Magazine: Alzheimers Res Ther.
Begin- en eindpagina:
Titel: Aß43 in human Alzheimer's disease: effects of active Aß42 immunization. Acta Neuropathol Commun.
Auteur: Jäkel L, Boche D, Nicoll JAR, Verbeek MM
Magazine: Acta Neuropathologica communications
Titel: Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis.
Auteur: Bridel C, van Wieringen WN, Zetterberg H, Tijms BM, Teunissen CE; and the NFL Group, Alvarez-Cermeño JC, Andreasson U, Axelsson M, Bäckström DC, Bartos A, Bjerke M, Blennow K, Boxer A, Brundin L, Burman J, Christensen T, Fialová L, Forsgren L, Frederiksen JL, Gisslén M, Gray E, Gunnarsson M, Hall S, Hansson O, Herbert MK, Jakobsson J, Jessen-Krut J, Janelidze S, Johannsson G, Jonsson M, Kappos L, Khademi M, Khalil M, Kuhle J, Landén M, Leinonen V, Logroscino G, Lu CH, Lycke J, et al
Magazine: JAMA Neurol
Begin- en eindpagina:
Titel: Antisense Oligonucleotide-Induced Amyloid Precursor Protein Splicing Modulation as a Therapeutic Approach for Dutch-Type Cerebral Amyloid Angiopath.
Auteur: Daoutsali E, Hailu TT, Buijsen RAM, Pepers BA, van der Graaf LM, Verbeek MM, Curtis D, de Vlaam T, van Roon-Mom WMC.
Magazine: Nucleic Acids Research
Titel: Cerebrospinal fluid levels of the neurotrophic factor neuroleukin are increased in early Alzheimer's disease, but not in cerebral amyloid angiopathy
Auteur: De Kort AM, Kuiperij HB, Alcolea D, Kersten I, Versleijen AAM, Greenberg SM, Stoops E, Schreuder FHBM, Klijn CJM, Lleó A, Claassen JAHR, Verbeek MM
Magazine: Alzheimer Research and Therapy
Titel: Autoimmune Encephalitis Resembling Dementia Syndromes
Auteur: Bastiaansen AEM, van Steenhoven RW, de Bruijn MAAM, Crijnen YS, van Sonderen A, van Coevorden-Hameete MH, Nühn MM, Verbeek MM, Schreurs MWJ, Sillevis Smitt PAE, de Vries JM, Jan de Jong F, Titulaer MJ.
Magazine: Neurol Neuroimmunol Neuroinflamm
Begin- en eindpagina:
Titel: Reply to "Decreased Cerebrospinal Fluid Amyloid Beta 38, 40, 42, and 43 Levels in Sporadic and Hereditary Cerebral Amyloid Angiopathy"
Auteur: de Kort AM, Kuiperij HB, Schreuder FHBM, Klijn CJM, Verbeek MM.
Magazine: Ann Neurol.
Begin- en eindpagina:
Titel: Reduced Levels of Cerebrospinal Fluid/Plasma Aß40 as an Early Biomarker for Cerebral Amyloid Angiopathy in RTg-DI Rats
Auteur: Zhu, Xiaoyue, Xu, Feng, Hoos, Michael D., Lee, Hedok, Benveniste, Helene, Van Nostrand, William E.
Magazine: International Journal of Molecular Sciences
Titel: Disturbed Balance in the Expression of MMP9 and TIMP3 in Cerebral Amyloid Angiopathy-Related Intracerebral Haemorrhage.
Auteur: Jäkel L, Kuiperij HB, Gerding LP, Custers EEM, van den Berg E, Jolink WMT, Schreuder FHBM, Küsters B, Klijn CJM, Verbeek MM.
Magazine: Acta Neuropathologica communications
Titel: . Reduced Influence of apoE on Aß43 Aggregation and Reduced Vascular Aß43 Toxicity as Compared with Aß40 and Aß42
Auteur: Jäkel L, Biemans EALM, Klijn CJM, Kuiperij HB, Verbeek MM.
Magazine: Molecular Neurobiology
Titel: Aß43 in human Alzheimer's disease: effects of active Aß42 immunization
Auteur: Jäkel L, Boche D, Nicoll JAR, Verbeek MM
Magazine: Acta Neuropathologica communications
Titel: Decreased ratios of matrix metalloproteinases to tissue-type inhibitors in cerebrospinal fluid in sporadic and hereditary cerebral amyloid angiopathy
Auteur: Vervuurt M, de Kort AM, Jäkel L, Kersten I, Abdo WF, Schreuder FHBM, Rasing I, Terwindt GM, Wermer MJH, Greenberg SM, Klijn CJM, Kuiperij HB, Verbeek MM.
Magazine: Alzheimers Res Ther
Begin- en eindpagina:
Titel: Prevalence of cerebral amyloid angiopathy: A systematic review and meta-analysis.
Auteur: Jäkel L, De Kort AM, Klijn CJM, Schreuder FHBM, Verbeek MM
Magazine: Alzheimers Dement
Begin- en eindpagina:
Titel: MFG-E8 (LACTADHERIN): a novel marker associated with cerebral amyloid angiopathy.
Auteur: Marazuela P, Solé M, Bonaterra-Pastra A, Pizarro J, Camacho J, Martínez-Sáez E, Kuiperij HB, Verbeek MM, de Kort AM, Schreuder FHBM, Klijn CJM, Castillo-Ribelles L, Pancorbo O, Rodríguez-Luna D, Pujadas F, Delgado P, Hernández-Guillamon M
Magazine: Acta Neuropathol Comm
Begin- en eindpagina:
Titel: Valuing biomarker diagnostics for dementia care: enhancing the reflection of patients, their care-givers and members of the wider public.
Auteur: van der Burg S, Schreuder FHBM, Klijn CJM, Verbeek MM.
Magazine: Med Health Care Philos
Begin- en eindpagina:
Titel: Apolipoprotein D: a potential biomarker for cerebral amyloid angiopathy. Neuropathol Appl Neurobiol.
Auteur: Kuiperij HB, Hondius DC, Kersten I, Versleijen AAM, Rozemuller AJM, Greenberg SM, Schreuder FHBM, Klijn CJM, Verbeek MM
Magazine: Neuropathology and Applied Neurobiology
Link: https://onlinelibrary.wiley.com/doi/full/10.1111/nan.12595
Titel: Phase II trial of natalizumab for the treatment of anti-Hu associated paraneoplastic neurological syndromes
Auteur: Bastiaansen AEM, de Jongste AHC, de Bruijn MAAM, Crijnen YS, Schreurs MWJ, Verbeek MM, Dumoulin DW, Taal W, Titulaer MJ, Sillevis Smitt PAE
Magazine: Neurooncol Adv
Begin- en eindpagina:
Titel: Cerebrospinal fluid levels of the neurotrophic factor neuroleukin are increased in early Alzheimer's disease, but not in cerebral amyloid angiopathy
Auteur: De Kort AM, Kuiperij HB, Alcolea D, Kersten I, Versleijen AAM, Greenberg SM, Stoops E, Schreuder FHBM, Klijn CJM, Lleó A, Claassen JAHR, Verbeek MM
Magazine: Alzheimers Res
Begin- en eindpagina:
Titel: Mapping the multicausality of Alzheimer's disease through group model building
Auteur: Uleman JF, Melis RJF, Quax R, van der Zee EA, Thijssen D, Dresler M, van de Rest O, van der Velpen IF, Adams HHH, Schmand B, de Kok IMCM, de Bresser J, Richard E, Verbeek M, Hoekstra AG, Rouwette EAJA, Olde Rikkert MGM
Magazine: Geroscience
Begin- en eindpagina:
Titel: Apolipoprotein D: a potential biomarker for cerebral amyloid angiopathy.
Auteur: Kuiperij HB, Hondius DC, Kersten I, Versleijen AAM, Rozemuller AJM, Greenberg SM, Schreuder FHBM, Klijn CJM, Verbeek MM
Magazine: Neuropathol Appl Neurobiol
Begin- en eindpagina:
Titel: Normal cerebrospinal fluid concentrations of PDGFRß in patients with cerebral amyloid angiopathy and Alzheimer's disease
Auteur: De Kort AM, Kuiperij HB, Kersten I, Versleijen AAM, Schreuder FHBM, Van Nostrand WE, Greenberg SM, Klijn CJM, Claassen JAHR, Verbeek MM
Magazine: Alzheimers Dement
Begin- en eindpagina:
Titel: Iatrogenic Cerebral Amyloid Angiopathy Post Neurosurgery: Frequency, Clinical Profile, Radiological Features, and Outcome
Auteur: Kaushik K, van Etten ES, Siegerink B, Kappelle LJ, Lemstra AW, Schreuder FHBM, Klijn CJM, Peul WC, Terwindt GM, van Walderveen MAA, Wermer MJH
Magazine: Stroke
Begin- en eindpagina:
Titel: Decreased Cerebrospinal Fluid Amyloid ß 38, 40, 42, and 43 Levels in Sporadic and Hereditary Cerebral Amyloid Angiopathy.
Auteur: De Kort AM, Kuiperij HB, Marques TM, Jäkel L, van den Berg E, Kersten I, van Berckel-Smit HEP, Duering M, Stoops E, Abdo WF, Rasing I, Voigt S, Koemans EA, Kaushik K, Warren AD, Greenberg SM, Brinkmalm G, Terwindt GM, Wermer MJH, Schreuder FHBM, Klijn CJM, Verbeek MM.
Magazine: Ann Neurol.
Begin- en eindpagina:
Titel: MFG-E8 (LACTADHERIN): a novel marker associated with cerebral amyloid angiopathy.
Auteur: Marazuela P, Solé M, Bonaterra-Pastra A, Pizarro J, Camacho J, Martínez-Sáez E, Kuiperij HB, Verbeek MM, de Kort AM, Schreuder FHBM, Klijn CJM, Castillo-Ribelles L, Pancorbo O, Rodríguez-Luna D, Pujadas F, Delgado P, Hernández-Guillamon M.
Magazine: Acta Neuropathologica communications
Titel: Disturbed Balance in the Expression of MMP9 and TIMP3 in Cerebral Amyloid Angiopathy-Related Intracerebral Haemorrhage
Auteur: Jäkel L, Kuiperij HB, Gerding LP, Custers EEM, van den Berg E, Jolink WMT, Schreuder FHBM, Küsters B, Klijn CJM, Verbeek MM
Magazine: Acta Neuropathol Comm
Begin- en eindpagina:
Titel: Reduced Influence of apoE on Aß43 Aggregation and Reduced Vascular Aß43 Toxicity as Compared with Aß40 and Aß42.
Auteur: Jäkel L, Biemans EALM, Klijn CJM, Kuiperij HB, Verbeek MM
Magazine: Mol Neurobiol
Begin- en eindpagina:
Titel: Cerebrospinal Fluid Panel of Synaptic Proteins in Cerebral Amyloid Angiopathy and Alzheimer's Disease
Auteur: van den Berg E, Nilsson J, Kersten I, Brinkmalm G, de Kort AM, Klijn CJM, Schreuder FHBM, Jäkel L, Gobom J, Portelius E, Zetterberg H, Brinkmalm A, Blennow K, Kuiperij HB, Verbeek MM
Magazine: J Alzheimers Dis
Begin- en eindpagina:
Titel: Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis
Auteur: Bridel C, van Wieringen WN, Zetterberg H, Tijms BM, Teunissen CE; and the NFL Group, Alvarez-Cermeño JC, Andreasson U, Axelsson M, Bäckström DC, Bartos A, Bjerke M, Blennow K, Boxer A, Brundin L, Burman J, Christensen T, Fialová L, Forsgren L, Frederiksen JL, Gisslén M, Gray E, Gunnarsson M, Hall S, Hansson O, Herbert MK, Jakobsson J, Jessen-Krut J, Janelidze S, Johannsson G, Jonsson M, Kappos L, Khademi M, Khalil M, Kuhle J, Landén M, Leinonen V, Logroscino G, Lu CH, Lycke J, Magdalinou N
Magazine: JAMA Neurology
Titel: Desirability of Diagnosing Sporadic Cerebral Amyloid Angiopathy with Biological Evidence
Auteur: Abdulrahman H, Smedinga M, Verbeek MM, Klijn CJM, Richard E, Perry M.
Magazine: J Alzheimers Dis
Begin- en eindpagina:
Titel: Aß43 in human Alzheimer's disease: effects of active Aß42 immunization
Auteur: Jäkel L, Biemans EALM, Klijn CJM, Kuiperij HB, Verbeek MM.
Magazine: Acta Neuropathol Comm
Begin- en eindpagina:
Titel: Validation of the LUMIPULSE automated immunoassay for the measurement of core AD biomarkers in cerebrospinal fluid.
Auteur: Gobom J, Parnetti L, Rosa-Neto P, Vyhnalek M, Gauthier S, Cataldi S, Lerch O, Laczo J, Cechova K, Clarin M, Benet AL, Pascoal TA, Rahmouni N, Vandijck M, Huyck E, Le Bastard N, Stevenson J, Chamoun M, Alcolea D, Lleó A, Andreasson U, Verbeek MM, Bellomo G, Rinaldi R, Ashton NJ, Zetterberg H, Sheardova K, Hort J, Blennow K.
Magazine: Clin Chem Lab Med
Begin- en eindpagina:
Titel: Neuroleukin: a potential cerebrospinal fluid biomarker for Alzheimer's disease
Auteur: A.M. de Kort, H.B. Kuiperij, I. Kersten, A.A.M. Versleijen, F.H.B.M. Schreuder, C.J.M. Klijn, J.A.H.R. Claassen, M.M. Verbeek
Titel: A disbalance of matrix metalloproteinases and their inhibitors in the cerebrospinal fluid from patients with cerebral amyloid angiopathy
Auteur: H.B. Kuiperij, M. Vervuurt, A.M. de Kort, I. Kersten, F.H.B.M. Schreuder, C.J.M. Klijn, M.M. Verbeek
Titel: NFL AND GFAP IN EARLY AND ADVANCED CEREBRAL AMYLOID ANGIOPATHY
Auteur: I. Rasing, MD1*; S. Voigt, BSc1*; E.A. Koemans, MD1; A. de Kort, MSc5, T.W. van Harten, MSc2; E.S. van Etten, MD1; E.W. van Zwet, MSc, PhD3; E. Stoops4; K. Dewaele4; H.B. Kuiperij, PhD5; C.J.M. Klijn, MD, PhD5; W.M.C. van Roon-Mom, MSc, PhD6; M.J.P. van Osch, PhD2; M.A.A. van Walderveen, MD, PhD2; M. M. Verbeek, MSc, PhD5; G.M. Terwindt MD, PhD1**; M.J.H. Wermer, MD, PhD1**
Titel: Urokinase plasminogen activator (uPA) as a novel biomarker for cerebral amyloid angiopathy
Auteur: Vervuurt, de Kort, Kuiperij, Klijn, Schreuder, van Nostrand, Verbeek
Titel: Neuroleukin and platelet-derived growth factor receptor-beta: potential cerebrospinal fluid biomarkers for Alzheimer’s disease
Auteur: A. de Kort, H.B. Kuiperij, I. Kersten, A.A.M. Versleijen, F.H.B.M. Schreuder, C.J.M. Klijn, J.A.H.R. Claassen, M.M. Verbeek
Titel: Assay development for cerebrospinal fluid biomarkers for cerebral amyloid angiopathy
Auteur: I. Kersten, H.B. Kuiperij, H. Vanderstichele, H.J. Wessels, F.H.B.M. Schreuder, C.J.M. Klijn, M.M. Verbeek
Titel: Prevalence of sporadic cerebral amyloid angiopathy: A Systematic Review and Meta-Analysis
Auteur: L. Jäkel, A. M. De Kort, C.J.M. Klijn, F.H.B.M. Schreuder, M.M. Verbeek
Titel: Altered expression of MMP9, TIMP3, and Claudin-5 in cerebral amyloid angiopathy related-intracerebral haemorrhage
Auteur: Lieke Jäkel, H. Bea Kuiperij, Lara P. Gerding, Emma Custers, Wilmar M.T. Jolink, Floris H.B.M. Schreuder, Benno Küsters, Catharina J.M. Klijn, Marcel M. Verbeek
Titel: Apolipoprotein D: a potential biomarker for cerebral amyloid angiopathy
Auteur: H.B. Kuiperij, D.C. Hondius, I. Kersten, A.A.M. Versleijen, A.J.M. Rozemuller, S.M. Greenberg, F.H.B.M. Schreuder, C. J.M. Klijn, M.M. Verbeek
Titel: Platelet-derived growth factor receptor-beta as a potential CSF biomarker for Alzheimer’s Disease
Auteur: H.B. Kuiperij, A.M. de Kort, I. Kersten, A.A.M. Versleijen, F.H.B.M. Schreuder, W.E Van Nostrand, S.M. Greenberg, C.J.M. Klijn, J.A.H.R. Claassen, M.M. Verbeek
Titel: Normal cerebrospinal fluid concentrations of platelet-derived growth factor receptor-ß in patients with cerebral amyloid angiopathy and Alzheimer’s disease
Auteur: H.B. Kuiperij, A.M. de Kort, I. Kersten, A.A.M. Versleijen, F.H.B.M. Schreuder, W.E Van Nostrand, S.M. Greenberg, C.J.M. Klijn, J.A.H.R. Claassen, M.M. Verbeek
Titel: Amyloid-beta peptides in CSF discriminate cerebral amyloid angiopathy from controls
Auteur: H.B. Kuiperij, A.M. de Kort, T.M. Marques, F.H.B.M. Schreuder, C.J.M. Klijn, E. Stoops, G. Brinkmalm, E. Portelius, E. Gkanatsiou, M.M. Verbeek
Titel: Assay development for cerebrospinal fluid biomarkers for cerebral amyloid angiopathy
Auteur: I. Kersten, H.B. Kuiperij, H. Vanderstichele, H.J. Wessels, F.H.B.M. Schreuder, C.J.M. Klijn, M.M. Verbeek
Titel: Prevalence of sporadic CAA in healthy elderly, dementia patients and patients with ICH: A Systematic Review
Auteur: L. Jäkel, A. M. De Kort, C.J.M. Klijn, F.H.B.M. Schreuder, M.M. Verbeek
Titel: Development of novel CSF biomarkers for cerebral amyloid angiopathy
Auteur: H.B. Kuiperij
Titel: BIOmarkers for cogNitive Impairment due to Cerebral Amyloid Angiopathy (BIONIC)
Auteur: Anna de Kort, H. Bea Kuiperij, Gisela Terwindt, Marieke Wermer, Hugo VanderStichele, Floris B.P.M. Schreuder, William E. VanNostrand, Edo Richard, Catharina J.M. Klijn, Marcel M. Verbeek
Titel: Urokinase plasminogen activator (uPA) as a novel biomarker for cerebral amyloid angiopathy
Auteur: Vervuurt M., Zhu X., Schrader J., de Kort A., Marques T.M., Kersten I., Kuiperij H.B., Klijn C.J.M., van Nostrand W.E., Verbeek M.M.
Titel: Apolipoprotein D: a potential biomarker for cerebral amyloid angiopathy
Auteur: H.B. Kuiperij, D.C. Hondius, I. Kersten, A.A.M. Versleijen, A.J.M. Rozemuller, S.M. Greenberg, F.H.B.M. Schreuder, C. J.M. Klijn, M.M. Verbeek
Titel: Apolipoprotein D: a potential biomarker for cerebral amyloid angiopathy
Auteur: H.B. Kuiperij, D.C. Hondius, I. Kersten, A.A.M. Versleijen, A.J.M. Rozemuller, S.M. Greenberg, F.H.B.M. Schreuder, C. J.M. Klijn, M.M. Verbeek
Titel: BIOmarkers for cogNitive Impairment due to Cerebral Amyloid Angiopathy (BIONIC)
Auteur: Anna de Kort, H. Bea Kuiperij, Gisela Terwindt, Marieke Wermer, Hugo VanderStichele, Floris B.P.M. Schreuder, William E. VanNostrand, Edo Richard, Catharina J.M. Klijn, Marcel M. Verbeek
Titel: Apolipoprotein D: a potential biomarker for cerebral amyloid angiopathy
Auteur: H.B. Kuiperij, D.C. Hondius, I. Kersten, A.A.M. Versleijen, A.J.M. Rozemuller, S.M. Greenberg, F.H.B.M. Schreuder, C.J.M. Klijn, M.M. Verbeek

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Samenvatting van de aanvraag

Cerebral Amyloid Angiopathy (CAA) results from the accumulation of the amyloid ß protein (Aß) within and along cerebral arteries, arterioles and capillaries. CAA is a common co-pathology in AD and approximately 25% of AD patients have severe CAA. CAA, either as a sporadic or familial trait, is an important cause of lobar intracerebral hemorrhage (ICH), but also of cognitive decline. Survivors of ICH have a 28% risk of developing dementia within four years after the ICH, and almost 75% of the patients with CAA, but without clinical signs of ICH, develop dementia after 5 years. Currently available diagnostic tools ( the so-called “Boston criteria”, based on microbleeds or superficial siderosis on MRI; amyloid PET) are insufficient in demonstrating the burden of CAA in vivo in patients with dementia or ICH. These Boston criteria do not provide definitive proof of the disease, and using them at best yields a diagnosis of “probable CAA”. Moreover, early diagnosis of CAA is hampered since only the late-stage features of CAA are visible on MRI. Whereas biomarkers to detect cerebral parenchymal lesions in dementia patients are available (e.g. PET scans or CSF biomarkers) and used in clinical practice, there is a paucity in biomarkers to detect CAA during life in stages prior to hemorrhages occur. Not only will such biomarkers aid in specific detection of CAA prior to the occurrence of hemorrhagic lesions, such biomarkers will also aid in establishing the contribution of CAA to cognitive decline. Furthermore, CAA is linked to the occurrence of amyloid-related imaging abnormalities (ARIA) as a consequence of passive immunization. Anti-Aß immunotherapy emerges as a promising therapy for the treatment of Alzheimer disease (AD) patients, but its application is hampered by development of ARIA, which may may affect up to 50% of treated patients. Tools to estimate the risk of developing ARIA in patients participating in immunization trials are not available, and specific biomarkers of CAA may provide such tools to select patients for immunotherapy with the aim of avoiding the occurrence of ARIA. This project aims to develop and validate novel body fluid biomarkers for CAA. Previously, we have demonstrated that CSF Aß40 levels may identify CAA already in a presymptomatic stage of CAA. In addition, we have identified several other potential body fluid biomarkers of CAA that may have diagnostic value which is not possible by currently available (neuroimaging or other) methods. We propose that abnormal levels of body fluid biomarkers for CAA may serve as a tool to (1) identify CAA at early stages of disease; (2) quantify the contribution of CAA to cognitive decline in dementia patients, and (3) identify those AD patients at risk of developing ARIA in immunotherapy trials who should therefore be excluded from participation. Importantly, future implementation of these novel biomarkers may proceed along various different scenarios. In our previous study we selected the most appropriate, and asked different groups of patients with CAA or dementia as well as their informal care-givers and healthy elderly people to reflect on their desirability, using a cards method. In this project we build on the results of this earlier study. By investigating the preferences and values of users such as patients, clinicians, nurses and informal caregivers, this project anticipates possible barriers that may emerge during the implementation phase: patients’ and clinicians’ lack of acceptance, or even resistance against, novel biomarkers could hamper a swift implementation later on. By means of the planned qualitative research (focus group interviews with patients, care-givers and clinicians) and a workshop, we aim to acquire insight into the acceptance/desirability of these biomarkers by envisioned users and tailor the implementation strategy to their preferences.

Kenmerken

Projectnummer:
733050822
Looptijd: 100%
Looptijd: 100 %
2018
2023
Onderdeel van programma:
Gerelateerde subsidieronde:
Projectleider en penvoerder:
dr. ir. M.M. Verbeek
Verantwoordelijke organisatie:
Radboud Universitair Medisch Centrum