Title

Alzheimer's Disease Normative Cerebrospinal Fluid Biomarkers Validated In Pet Amyloid-β Characterized Subjects From The Australian Imaging, Biomarkers And Lifestyle (AIBL) Study

Document Type

Journal Article

Publisher

IOS Press

Faculty

Faculty of Health, Engineering and Science

School

School of Medical Sciences, Centre of Excellence for Alzheimer's Disease Research And Care

RAS ID

19872

Comments

Originally published as : Li, Q. X., Villemagne, V. L., Doecke, J. D., Rembach, A., Sarros, S., Varghese, S., ... & Rumble, R. L. (2015). Alzheimer’s Disease Normative Cerebrospinal Fluid Biomarkers Validated in PET Amyloid-β Characterized Subjects from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Journal of Alzheimer's Disease,48(1), 175-187. Original article available here

Abstract

Background: The cerebrospinal fluid (CSF) amyloid-β (Aβ)1-42, total-tau (T-tau), and phosphorylated-tau (P-tau181P) profile has been established as a valuable biomarker for Alzheimer's disease (AD). Objective: The current study aimed to determine CSF biomarker cut-points using positron emission tomography (PET) Aβ imaging screened subjects from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, as well as correlate CSF analyte cut-points across a range of PET Aβ amyloid ligands. Methods: Aβ pathology was determined by PET imaging, utilizing 11C-Pittsburgh Compound B, 18F-flutemetamol, or 18Fflorbetapir, in 157 AIBL participants who also underwent CSF collection. Using anINNOTEST assay, cut-points were established (Aβ 1-42 >544 ng/L, T-tau/L, and P-tau181P/L) employing a rank based method to define a positive CSF in the sub-cohort of amyloid-PET negative healthy participants (n = 97), and compared with the presence of PET demonstrated AD pathology. Results: CSF Aβ 1-42 was the strongest individual biomarker, detecting cognitively impaired PET positive mild cognitive impairment (MCI)/AD with 85% sensitivity and 91% specificity. The ratio of P-tau181P or T-tau to Aβ1-42 provided greater accuracy, predicting MCI/AD with Aβ pathology with ?92% sensitivity and specificity. Cross-validated accuracy, using all three biomarkers or the ratio of P-tau or T-tau to Aβ 1-42 to predict MCI/AD, reached ?92% sensitivity and specificity. Conclusions: CSF Aβ1-42 levels and analyte combination ratios demonstrated very high correlation with PET Aβ imaging. Our study offers additional support for CSF biomarkers in the early and accurate detection of AD pathology, including enrichment of patient cohorts for treatment trials even at the pre-symptomatic stage.

DOI

10.3233/JAD-150247

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