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A High Throughput, Multiplexed and Targeted Proteomic CSF Assay to Quantify Neurodegenerative Biomarkers and Apolipoprotein E Isoforms Status
Published on: October 20, 2016
Diagnostic Accuracy of Cerebrospinal Fluid Amyloid-β Isoforms for Early and Differential Dementia Diagnosis
Hanne Struyfs1, Bianca Van Broeck2, Maarten Timmers3
1Reference Center for Biological Markers of Dementia (BIODEM), and Biobank, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Background:
Overlapping cerebrospinal fluid biomarkers (CSF) levels between Alzheimer's disease (AD) and non-AD patients decrease differential diagnostic accuracy of the AD core CSF biomarkers. Amyloid-β (Aβ) isoforms might improve the AD versus non-AD differential diagnosis.
Objective:
To determine the added diagnostic value of Aβ isoforms, Aβ(1-37), Aβ(1-38), and Aβ(1-40), as compared to the AD CSF biomarkers Aβ(1-42), T-tau, and P-tau(181P).
Methods:
CSF from patients with dementia due to AD (n = 50), non-AD dementias (n = 50), mild cognitive impairment due to AD (n = 50) and non-demented controls (n = 50) was analyzed with a prototype multiplex assay using MSD detection technology. The non-AD group consisted of frontotemporal dementia (FTD; n = 17), dementia with Lewy bodies (DLB; n = 17), and vascular dementia (n = 16).
Results:
Aβ(1-37) and Aβ(1-38) increased accuracy to differentiate AD from FTD or DLB. Aβ(1-37), Aβ(1-38), and Aβ(1-40) levels correlated with Mini-Mental State Examination scores and disease duration in dementia due to AD. The Aβ(1-42)/Aβ(1-40) ratio improved diagnostic performance of Aβ(1-42) in most differential diagnostic situations. Aβ(1-42) levels were lower in APOE ε4 carriers compared to non-carriers.
Conclusions:
Aβ isoforms help to differentiate AD from FTD and DLB. Aβ isoforms increase diagnostic performance of Aβ(1-42). In contrast to Aβ1-42, Aβ isoforms seem to be correlated with disease severity in AD. Adding the Aβ isoforms to the current biomarker panel could enhance diagnostic accuracy.
Insights
Amyloid-beta (Aβ) isoforms in cerebrospinal fluid improve the differential diagnosis of Alzheimer's disease (AD) from other dementias. These Aβ isoforms enhance the diagnostic accuracy of existing AD biomarkers.
Area of Science:
- Neurology
- Biochemistry
- Biomarker Discovery
Background:
- Cerebrospinal fluid (CSF) biomarker overlap between Alzheimer's disease (AD) and non-AD conditions limits diagnostic accuracy.
- Amyloid-beta (Aβ) isoforms may offer improved differentiation between AD and non-AD pathologies.
Purpose of the Study:
- To evaluate the diagnostic value of Aβ(1-37), Aβ(1-38), and Aβ(1-40) isoforms.
- To compare their diagnostic utility against established AD CSF biomarkers: Aβ(1-42), T-tau, and P-tau(181P).
Main Methods:
- CSF samples from 200 participants (50 AD dementia, 50 non-AD dementias, 50 mild cognitive impairment due to AD, 50 controls) were analyzed.
- A prototype multiplex assay with MSD detection technology was employed.
- Non-AD dementias included frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), and vascular dementia.
Main Results:
- Aβ(1-37) and Aβ(1-38) improved differentiation between AD and FTD or DLB.
- Aβ(1-37), Aβ(1-38), and Aβ(1-40) correlated with cognitive status (MMSE) and disease duration in AD.
- The Aβ(1-42)/Aβ(1-40) ratio enhanced the diagnostic performance of Aβ(1-42).
- Lower Aβ(1-42) levels were observed in APOE ε4 carriers.
Conclusions:
- Aβ isoforms are valuable in distinguishing AD from FTD and DLB.
- These isoforms augment the diagnostic performance of Aβ(1-42).
- Unlike Aβ(1-42), Aβ isoforms correlate with AD disease severity.
- Incorporating Aβ isoforms into biomarker panels can enhance diagnostic accuracy for AD.
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