Temporal Ordering of Biomarkers in Dutch-Type Hereditary Cerebral Amyloid Angiopathy-Reference-Cited by-同舟云学术

Temporal Ordering of Biomarkers in Dutch-Type Hereditary Cerebral Amyloid Angiopathy

Published:2024-04 Issue:4 Volume:55 Page:954-962
ISSN:0039-2499
Container-title:Stroke
language:en
Short-container-title:Stroke

Author:

Koemans Emma A.¹,Rasing Ingeborg¹^ORCID,Voigt Sabine¹²^ORCID,van Harten Thijs W.²^ORCID,van der Zwet Reinier G.J.¹^ORCID,Kaushik Kanishk¹^ORCID,Schipper Manon R.²^ORCID,van der Weerd Nelleke¹^ORCID,van Zwet Erik W.³^ORCID,van Etten Ellis S.¹^ORCID,van Osch Matthias J.P.²^ORCID,Kuiperij Bea⁴^ORCID,Verbeek Marcel M.⁴^ORCID,Terwindt Gisela M.¹^ORCID,Greenberg Steven M.⁵^ORCID,van Walderveen Marianne A.A.²^ORCID,Wermer Marieke J.H.¹⁶^ORCID

Affiliation:

1. Departments of Neurology (E.A.K., I.R., S.V., R.G.J.v.d.Z., K.K., N.v.d.W., E.S.v.E., G.M.T., M.J.H.W.), Leiden University Medical Center, the Netherlands.

2. Radiology (S.V., T.W.v.H., M.R.S., M.J.v.P.O., M.A.A.v.W.), Leiden University Medical Center, the Netherlands.

3. Biostatistics (E.W.v.Z.), Leiden University Medical Center, the Netherlands.

4. Department Neurology and Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen (B.K., M.M.V.).

5. J Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (S.M.G.).

6. Department of Neurology, University Medical Center Groningen, the Netherlands (M.J.H.W.).

Abstract

BACKGROUND: The temporal ordering of biomarkers for cerebral amyloid angiopathy (CAA) is important for their use in trials and for the understanding of the pathological cascade of CAA. We investigated the presence and abnormality of the most common biomarkers in the largest (pre)symptomatic Dutch-type hereditary CAA (D-CAA) cohort to date. METHODS: We included cross-sectional data from participants with (pre)symptomatic D-CAA and controls without CAA. We investigated CAA-related cerebral small vessel disease markers on 3T-MRI, cerebrovascular reactivity with functional 7T-MRI (fMRI) and amyloid-β 40 and amyloid-β 42 levels in cerebrospinal fluid. We calculated frequencies and plotted biomarker abnormality according to age to form scatterplots. RESULTS: We included 68 participants with D-CAA (59% presymptomatic, mean age, 50 [range, 26–75] years; 53% women), 53 controls (mean age, 51 years; 42% women) for cerebrospinal fluid analysis and 36 controls (mean age, 53 years; 100% women) for fMRI analysis. Decreased cerebrospinal fluid amyloid-β 40 and amyloid-β 42 levels were the earliest biomarkers present: all D-CAA participants had lower levels of amyloid-β 40 and amyloid-β 42 compared with controls (youngest participant 30 years). Markers of nonhemorrhagic injury (>20 enlarged perivascular spaces in the centrum semiovale and white matter hyperintensities Fazekas score, ≥2, present in 83% [n=54]) and markers of impaired cerebrovascular reactivity (abnormal BOLD amplitude, time to peak and time to baseline, present in 56% [n=38]) were present from the age of 30 years. Finally, markers of hemorrhagic injury were present in 64% (n=41) and only appeared after the age of 41 years (first microbleeds and macrobleeds followed by cortical superficial siderosis). CONCLUSIONS: Our results suggest that amyloid biomarkers in cerebrospinal fluid are the first to become abnormal in CAA, followed by MRI biomarkers for cerebrovascular reactivity and nonhemorrhagic injury and lastly hemorrhagic injury. This temporal ordering probably reflects the pathological stages of CAA and should be taken into account when future therapeutic trials targeting specific stages are designed.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Reference31 articles.

1. Prevalence of cerebral amyloid angiopathy: A systematic review and meta‐analysis

2. Sporadic Cerebral Amyloid Angiopathy: Pathophysiology, Neuroimaging Features, and Clinical Implications

3. The Boston criteria version 2.0 for cerebral amyloid angiopathy: a multicentre, retrospective, MRI–neuropathology diagnostic accuracy study

4. Hereditary Cerebral Hemorrhage with Amyloidosis-Dutch Type (HCHWA-D): I - A Review of Clinical, Radiologic and Genetic Aspects

5. The Cerebral β-Amyloid Angiopathies: Hereditary and Sporadic