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Decreased cerebrospinal fluid amyloid β 38, 40, 42, and 43 levels in sporadic and hereditary cerebral amyloid angiopathy
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 ...
Show moreObjective
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).
Show less- All authors
- Kort, A.M. de; Kuiperij, H.B.; Marques, T.M.; Jäkel, L.; Berg, E. van den; Kersten, I.; Berckel-Smit, H.E.P. van; Duering, M.; Stoops, E.; Abdo, W.F.; Rasing, I.; Voigt, S.; Koemans, E.A.; Kaushik, K.; Warren, A.D.; Greenberg, S.M.; Brinkmalm, G.; Terwindt, G.M.; Wermer, M.J.H.; Schreuder, F.H.B.M.; Klijn, C.J.M.; Verbeek, M.M.
- Date
- 2023-02-20
- Journal
- Annals of Neurology
- Volume
- 93
- Issue
- 6
- Pages
- 1173 - 1186