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Updated: May 15, 2026
A High Throughput, Multiplexed and Targeted Proteomic CSF Assay to Quantify Neurodegenerative Biomarkers and Apolipoprotein E Isoforms Status
Published on: October 20, 2016
Can MRI screen for CSF biomarkers in neurodegenerative disease?
Corey T McMillan1, Brian Avants, David J Irwin
1Department of Neurology, University of Pennsylvania, Philadelphia, USA. mcmillac@mail.med.upenn.edu
Objective:
Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD) may have overlapping clinical presentations despite distinct underlying neuropathologies, thus making in vivo diagnosis challenging. In this study, we evaluate the utility of MRI as a noninvasive screening procedure for the differential diagnosis of AD and FTLD.
Methods:
We recruited 185 patients with a clinically diagnosed neurodegenerative disease consistent with AD or FTLD who had a lumbar puncture and a volumetric MRI. A subset of 32 patients had genetic or autopsy-confirmed AD or FTLD. We used singular value decomposition to decompose MRI volumes and linear regression and cross-validation to predict CSF total tau (tt) and β-amyloid (Aβ(1-42)) ratio (tt/Aβ) in patients with AD and patients with FTLD. We then evaluated accuracy of MRI-based predicted tt/Aβ using 4 converging sources including neuroanatomic visualization and categorization of a subset of patients with genetic or autopsy-confirmed AD or FTLD.
Results:
Regression analyses showed that MRI-predicted tt/Aβ is highly related to actual CSF tt/Aβ. In each group, both predicted and actual CSF tt/Aβ have extensively overlapping neuroanatomic correlates: low tt/Aβ consistent with FTLD is related to ventromedial prefrontal regions while high tt/Aβ consistent with AD is related to posterior cortical regions. MRI-predicted tt/Aβ is 75% accurate at identifying underlying diagnosis in patients with known pathology and in clinically diagnosed patients with known CSF tt/Aβ levels.
Conclusion:
MRI may serve as a noninvasive procedure that can screen for AD and FTLD pathology as a surrogate for CSF biomarkers.
Insights
Magnetic Resonance Imaging (MRI) can noninvasively screen for Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD) pathology. This MRI approach accurately predicts cerebrospinal fluid biomarkers, aiding differential diagnosis.
Area of Science:
- Neuroimaging
- Neuropathology
- Biomarker Discovery
Background:
- Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD) present similar clinical symptoms, complicating accurate in vivo diagnosis due to distinct underlying pathologies.
- Current diagnostic methods often rely on invasive procedures or complex biomarker analysis, highlighting the need for accessible screening tools.
Purpose of the Study:
- To evaluate the efficacy of Magnetic Resonance Imaging (MRI) as a noninvasive screening tool for differentiating between AD and FTLD.
- To assess MRI's ability to predict cerebrospinal fluid (CSF) biomarker ratios indicative of AD or FTLD pathology.
Main Methods:
- Volumetric MRI and lumbar puncture were performed on 185 patients with clinically diagnosed AD or FTLD.
- Singular value decomposition and linear regression were used to predict the CSF total tau (tt) and β-amyloid (Aβ(1-42)) ratio (tt/Aβ) from MRI data.
- Accuracy was validated using neuroanatomic visualization and a subset of genetically or autopsy-confirmed cases.
Main Results:
- MRI-predicted tt/Aβ ratios showed a strong correlation with actual CSF tt/Aβ levels.
- Distinct neuroanatomic correlates were identified: ventromedial prefrontal regions for low tt/Aβ (FTLD) and posterior cortical regions for high tt/Aβ (AD).
- The MRI-based prediction achieved 75% accuracy in identifying the underlying diagnosis.
Conclusions:
- MRI can serve as a noninvasive screening procedure for AD and FTLD.
- MRI-based predictions of CSF biomarkers offer a surrogate for direct CSF analysis, potentially simplifying differential diagnosis.
