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Published on: March 7, 2019
Decreased Cerebrospinal Fluid Amyloid β 38, 40, 42, and 43 Levels in Sporadic and Hereditary Cerebral Amyloid
Anna M De Kort1, H Bea Kuiperij1, Tainá M Marques1
1Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behavior, Nijmegen, the Netherlands.
Insights
Cerebrospinal fluid amyloid-beta (Aβ) peptides can help diagnose cerebral amyloid angiopathy (CAA). Decreased levels of Aβ38, Aβ40, Aβ42, and Aβ43 in CSF show potential for diagnosing sporadic and Dutch-type CAA.
Area of Science:
- Neurology
- Biochemistry
- Biomarker Discovery
Background:
- Cerebral amyloid angiopathy (CAA) is characterized by vascular amyloid-beta (Aβ) accumulation.
- Cerebrospinal fluid (CSF) composition may offer diagnostic biomarkers for CAA.
Purpose of the Study:
- To investigate the diagnostic potential of CSF Aβ38, Aβ40, Aβ42, and Aβ43 peptides.
- To differentiate between sporadic CAA (sCAA), hereditary Dutch-type CAA (D-CAA), and Alzheimer disease (AD).
Main Methods:
- Quantification of Aβ peptides using immunoassays in discovery and validation cohorts.
- Inclusion of patients with sCAA, D-CAA, Alzheimer disease (AD), and healthy controls.
- Diagnostic accuracy assessed using receiver operating characteristic curve analysis (AUC).
Main Results:
- All measured Aβ peptides were decreased in sCAA and D-CAA patients compared to controls.
- Aβ42 and Aβ43 showed the most significant differences in sCAA patients versus controls (AUCs up to 0.95).
- Aβ38, Aβ40, and Aβ42 were decreased in sCAA compared to AD patients.
Conclusions:
- A combined panel of CSF Aβ peptides (Aβ38, Aβ40, Aβ42, Aβ43) can potentially differentiate sCAA from AD and controls.
- This panel also shows potential for differentiating D-CAA from controls.
- CSF Aβ peptide analysis offers a promising avenue for CAA diagnostics.
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.
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