Abstract
Backgroundβ-amyloid (Aβ) positron emission tomography (PET) imaging is currently the only Food and Drug Administration-approved method to support clinical diagnosis of Alzheimer’s disease (AD). However, numerous research studies support the use of cerebrospinal fluid (CSF) biomarkers, as a cost-efficient, quick and equally valid method to define AD pathology.MethodsUsing automated Elecsys® assays (Roche Diagnostics) for Aβ (1–42) (Aβ42), Aβ (1–40) (Aβ40), total tau (tTau) and phosphorylated tau (181P) (pTau), we examined CSF samples from 202 participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing cohort, to demonstrate the concordance with pathological AD via PET imaging.ResultsRatios Aβ42/Aβ40, tTau/Aβ42 and pTau/Aβ42 had higher receiver operator characteristic—area under the curve (all 0.94), and greater concordance with Aβ-PET (overall percentage agreement ~ 90%), compared with individual biomarkers.ConclusionStrong concordance between CSF biomarkers and Aβ-PET status was observed overall, including for cognitively normal participants, further strengthening the association between these markers of AD neuropathological burden for both developmental research studies and for use in clinical trials.
Highlights
Alzheimer’s disease (AD) pathology is recognised to evolve over an extended period before the onset of clinical symptoms [1], with homeostatic failure of the amyloid precursor protein cleavage appearing to be the primary pathogenic event [2,3,4]
The present study aimed to provide additional evidence in support of the relationship between cerebrospinal fluid (CSF) biomarkers and the neuropathological Aβ-positron emission tomography (PET) classification, further contributing to the National Institute on Ageing-Alzheimer’s Association (NIA-AA) research framework, which utilises the measurement of biomarkers to define an AD continuum [14, 15]
Gaussian mixture model (GMM) analysis for the ratios resulted in the following thresholds: 0.0673 (95% confidence interval [Confidence interval (CI)] 0.0612–0.0798) for Aβ42/Aβ40, 0.165 for total tau (tTau)/Aβ42 and 0.0159 for Phosphorylated tau (pTau)/Aβ42
Summary
Alzheimer’s disease (AD) pathology is recognised to evolve over an extended period before the onset of clinical symptoms [1], with homeostatic failure of the amyloid precursor protein cleavage appearing to be the primary pathogenic event [2,3,4]. The use of CSF biomarkers to support AD diagnosis is recommended in recent research diagnostic guidelines published by the International Work Group 2 [13], as well as the National Institute on Ageing-Alzheimer’s Association (NIA-AA) biological framework for AD [14]. The present study aimed to provide additional evidence in support of the relationship between CSF biomarkers and the neuropathological Aβ-PET classification, further contributing to the NIA-AA research framework, which utilises the measurement of biomarkers to define an AD continuum [14, 15]. The relationship between CSF biomarkers Aβ42, Aβ (1–40) (Aβ40), tTau and pTau (and their ratios) with the neuropathological Aβ-PET classification status was evaluated both across the full clinical disease spectrum, and in cognitively normal controls from the highly characterised Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing cohort
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