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CSF Biomarker Profile of Cerebral Amyloid Angiopathy: Diagnostic Performance and Imaging Correlates in a
Aida Fernández-Lebrero1,2,3, Joan Jiménez-Balado1, Greta García-Escobar1,2
1Hospital del Mar Research Institute, Barcelona, Spain.
Insights
Cerebral amyloid angiopathy (CAA) diagnosis is improved using cerebrospinal fluid (CSF) Aβ40 and Aβ42 biomarkers, especially when Alzheimer
Area of Science:
- Neurology
- Biomarker Discovery
- Neurodegenerative Diseases
Background:
- Cerebral amyloid angiopathy (CAA) frequently co-occurs with Alzheimer's disease (AD), complicating diagnosis in patients with cognitive impairment.
- The cerebrospinal fluid (CSF) biomarker profile of CAA, particularly with AD co-pathology, is not well understood.
- Understanding CSF biomarkers in CAA is crucial for accurate diagnosis and patient management.
Purpose of the Study:
- To characterize CSF biomarkers in patients with CAA, with and without AD co-pathology.
- To assess the diagnostic accuracy of CSF biomarkers for identifying CAA.
- To examine associations between CSF biomarkers and neuroimaging markers of CAA.
Main Methods:
- Included 261 participants: healthy controls (HC), CAA without AD (CAA-nonAD), CAA with AD (CAA-AD), and AD.
- Quantified CSF Aβ40, Aβ42, p-tau181, and t-tau using automated immunoassays.
- Utilized ANCOVA for group comparisons and ROC analyses for diagnostic performance assessment; examined associations with MRI markers.
Main Results:
- CSF Aβ40 was lower in CAA-nonAD and CAA-AD compared to AD and HC.
- CSF Aβ42 was reduced in CAA-AD and AD versus HC.
- Aβ40 demonstrated the highest diagnostic accuracy for CAA (AUC=0.73), while Aβ42 best discriminated coexisting CAA in AD patients (AUC=0.77).
Conclusions:
- CSF Aβ40 and Aβ42 offer complementary diagnostic value for identifying CAA, both alone and with AD co-pathology.
- Reduced CSF Aβ40 is linked to a higher burden of CAA-related vascular damage, indicating its role in vascular amyloid pathology.
- These findings enhance the utility of CSF biomarkers in diagnosing and understanding CAA.
Background:
Cerebral amyloid angiopathy (CAA) frequently co-occurs with Alzheimer's disease (AD), complicating diagnosis in patients with cognitive impairment. The CSF biomarker profile of CAA remains poorly understood, particularly with AD co-pathology. We aimed to characterize CSF biomarkers in CAA, assess diagnostic accuracy, and examine associations with neuroimaging markers.
Methods:
We included 261 participants from a hospital-based cohort, recruited from memory clinic outpatients and neurology inpatients. Groups comprised healthy controls (HC, n = 35), CAA without AD co-pathology (CAA-nonAD, n = 27), CAA with AD co-pathology (CAA-AD, n = 30), and AD (n = 169). CSF Aβ40, Aβ42, p-tau181, and t-tau were quantified using automated immunoassays. Group differences were tested using ANCOVA adjusted for age and sex. ROC analyses with 10-fold cross-validation and bootstrapping assessed diagnostic performance. Associations between CSF biomarkers and CAA-related MRI markers were examined using ANCOVA.
Results:
Aβ40 concentrations were lower in CAA-nonAD and CAA-AD compared to AD and HC (p-valuebf < 0.05). Aβ42 was reduced in CAA-AD and AD versus HC, with no difference between CAA-nonAD and AD. p-tau181 and t-tau were elevated in AD and CAA-AD compared with CAA-nonAD and HC (p-valuebf < 0.05). Aβ40 showed the highest diagnostic accuracy for CAA (AUC = 0.73; 95% CI: 0.66-0.80), followed by Aβ42 (AUC = 0.71; 95% CI: 0.64-0.78). In AD patients, Aβ42 best discriminated coexisting CAA (AUC = 0.77). Higher CAA-SVD burden scores were associated with lower Aβ40 (p-valuebf < 0.05).
Conclusions:
CSF Aβ40 and Aβ42 provide complementary diagnostic value for identifying CAA, both in isolation and with AD co-pathology. Reduced Aβ40 is associated with greater CAA-related vascular burden, supporting its role as a marker of vascular amyloid pathology.
