TY - JOUR
T1 - Decreased Cerebrospinal Fluid Amyloid β 38, 40, 42, and 43 Levels in Sporadic and Hereditary Cerebral Amyloid Angiopathy
AU - De Kort, Anna M.
AU - Kuiperij, H. Bea
AU - Marques, Tainá M.
AU - Jäkel, Lieke
AU - van den Berg, Emma
AU - Kersten, Iris
AU - van Berckel-Smit, Hugo E.P.
AU - Duering, Marco
AU - Stoops, Erik
AU - Abdo, Wilson F.
AU - Rasing, Ingeborg
AU - Voigt, Sabine
AU - Koemans, Emma A.
AU - Kaushik, Kanishk
AU - Warren, Andrew Davock
AU - Greenberg, Steven M.
AU - Brinkmalm, Gunnar
AU - Terwindt, Gisela M.
AU - Wermer, Marieke J.H.
AU - Schreuder, Floris H.B.M.
AU - Klijn, Catharina J.M.
AU - Verbeek, Marcel M.
N1 - Publisher Copyright:
© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
PY - 2023/6
Y1 - 2023/6
N2 - Objective: Vascular amyloid β (Aβ) accumulation is the hallmark of cerebral amyloid angiopathy (CAA). The composition of cerebrospinal fluid (CSF) of CAA patients may serve as a diagnostic biomarker of CAA. We studied the diagnostic potential of the peptides Aβ38, Aβ40, Aβ42, and Aβ43 in patients with sporadic CAA (sCAA), hereditary Dutch-type CAA (D-CAA), and Alzheimer disease (AD). Methods: Aβ peptides were quantified by immunoassays in a discovery group (26 patients with sCAA and 40 controls), a validation group (40 patients with sCAA, 40 patients with AD, and 37 controls), and a group of 22 patients with D-CAA and 54 controls. To determine the diagnostic accuracy, the area under the curve (AUC) was calculated using a receiver operating characteristic curve with 95% confidence interval (CI). Results: We found decreased levels of all Aβ peptides in sCAA patients and D-CAA patients compared to controls. The difference was most prominent for Aβ42 (AUC of sCAA vs controls for discovery: 0.90, 95% CI = 0.82–0.99; for validation: 0.94, 95% CI = 0.89–0.99) and Aβ43 (AUC of sCAA vs controls for discovery: 0.95, 95% CI = 0.88–1.00; for validation: 0.91, 95% CI = 0.83–1.0). All Aβ peptides except Aβ43 were also decreased in sCAA compared to AD (CSF Aβ38: AUC = 0.82, 95% CI = 0.71–0.93; CSF Aβ40: AUC = 0.88, 95% CI = 0.80–0.96; CSF Aβ42: AUC = 0.79, 95% CI = 0.66–0.92). Interpretation: A combined biomarker panel of CSF Aβ38, Aβ40, Aβ42, and Aβ43 has potential to differentiate sCAA from AD and controls, and D-CAA from controls. ANN NEUROL 2023;93:1173–1186.
AB - Objective: Vascular amyloid β (Aβ) accumulation is the hallmark of cerebral amyloid angiopathy (CAA). The composition of cerebrospinal fluid (CSF) of CAA patients may serve as a diagnostic biomarker of CAA. We studied the diagnostic potential of the peptides Aβ38, Aβ40, Aβ42, and Aβ43 in patients with sporadic CAA (sCAA), hereditary Dutch-type CAA (D-CAA), and Alzheimer disease (AD). Methods: Aβ peptides were quantified by immunoassays in a discovery group (26 patients with sCAA and 40 controls), a validation group (40 patients with sCAA, 40 patients with AD, and 37 controls), and a group of 22 patients with D-CAA and 54 controls. To determine the diagnostic accuracy, the area under the curve (AUC) was calculated using a receiver operating characteristic curve with 95% confidence interval (CI). Results: We found decreased levels of all Aβ peptides in sCAA patients and D-CAA patients compared to controls. The difference was most prominent for Aβ42 (AUC of sCAA vs controls for discovery: 0.90, 95% CI = 0.82–0.99; for validation: 0.94, 95% CI = 0.89–0.99) and Aβ43 (AUC of sCAA vs controls for discovery: 0.95, 95% CI = 0.88–1.00; for validation: 0.91, 95% CI = 0.83–1.0). All Aβ peptides except Aβ43 were also decreased in sCAA compared to AD (CSF Aβ38: AUC = 0.82, 95% CI = 0.71–0.93; CSF Aβ40: AUC = 0.88, 95% CI = 0.80–0.96; CSF Aβ42: AUC = 0.79, 95% CI = 0.66–0.92). Interpretation: A combined biomarker panel of CSF Aβ38, Aβ40, Aβ42, and Aβ43 has potential to differentiate sCAA from AD and controls, and D-CAA from controls. ANN NEUROL 2023;93:1173–1186.
UR - https://www.scopus.com/pages/publications/85148497042
U2 - 10.1002/ana.26610
DO - 10.1002/ana.26610
M3 - Article
C2 - 36707720
AN - SCOPUS:85148497042
SN - 0364-5134
VL - 93
SP - 1173
EP - 1186
JO - Annals of Neurology
JF - Annals of Neurology
IS - 6
ER -