Min Shi1, Lu Tang2, Jon B Toledo3, Carmen Ginghina1, Hua Wang4, Patrick Aro1, Poul H Jensen5, Daniel Weintraub3, Alice S Chen-Plotkin3, David J Irwin3, Murray Grossman3, Leo McCluskey3, Lauren B Elman3, David A Wolk3, Edward B Lee3, Leslie M Shaw3, John Q Trojanowski3, Jing Zhang6. 1. Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA. 2. Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA; Department of Neurology, Peking University Third Hospital, Beijing, China. 3. Departments of Pathology and Laboratory Medicine, Psychiatry, Neurology and Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 4. Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA; Department of Pathology, Peking University Health Science Centre and Third Hospital, Beijing, China. 5. DANDRITE-Danish Research Institute of Translational Neuroscience & Department of Biomedicine, University of Aarhus, Aarhus, Denmark. 6. Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA; Department of Pathology, Peking University Health Science Centre and Third Hospital, Beijing, China. Electronic address: zhangj@uw.edu.
Abstract
INTRODUCTION: The ability of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers (amyloid β peptide 1-42, total tau, and phosphorylated tau) to discriminate AD from related disorders is limited. Biomarkers for other concomitant pathologies (e.g., CSF α-synuclein [α-syn] for Lewy body pathology) may be needed to further improve the differential diagnosis. METHODS: CSF total α-syn, phosphorylated α-syn at Ser129, and AD CSF biomarkers were evaluated with Luminex immunoassays in 367 participants, followed by validation in 74 different neuropathologically confirmed cases. RESULTS: CSF total α-syn, when combined with amyloid β peptide 1-42 and either total tau or phosphorylated tau, improved the differential diagnosis of AD versus frontotemporal dementia, Lewy body disorders, or other neurological disorders. The diagnostic accuracy of the combined models attained clinical relevance (area under curve ∼0.9) and was largely validated in neuropathologically confirmed cases. DISCUSSION: Combining CSF biomarkers representing AD and Lewy body pathologies may have clinical value in the differential diagnosis of AD.
INTRODUCTION: The ability of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers (amyloid β peptide 1-42, total tau, and phosphorylated tau) to discriminate AD from related disorders is limited. Biomarkers for other concomitant pathologies (e.g., CSF α-synuclein [α-syn] for Lewy body pathology) may be needed to further improve the differential diagnosis. METHODS: CSF total α-syn, phosphorylated α-syn at Ser129, and AD CSF biomarkers were evaluated with Luminex immunoassays in 367 participants, followed by validation in 74 different neuropathologically confirmed cases. RESULTS: CSF total α-syn, when combined with amyloid β peptide 1-42 and either total tau or phosphorylated tau, improved the differential diagnosis of AD versus frontotemporal dementia, Lewy body disorders, or other neurological disorders. The diagnostic accuracy of the combined models attained clinical relevance (area under curve ∼0.9) and was largely validated in neuropathologically confirmed cases. DISCUSSION: Combining CSF biomarkers representing AD and Lewy body pathologies may have clinical value in the differential diagnosis of AD.
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