• Qiao-Xin Li, Victor L Villemagne, James D Doecke, Alan Rembach, Shannon Sarros, Shiji Varghese, Amelia McGlade, Katrina M Laughton, Kelly K Pertile, Christopher J Fowler, Rebecca L Rumble, Brett O Trounson, Kevin Taddei, Stephanie R Rainey-Smith, Simon M Laws, Joanne S Robertson, Lisbeth A Evered, Brendan Silbert, Kathryn A Ellis, Christopher C Rowe, S Lance Macaulay, David Darby, Ralph N Martins, David Ames, Colin L Masters, Steven Collins, and AIBL Research Group.
• Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia.
• J. Alzheimers Dis. 2015 Jan 1; 48 (1): 175-87.

BackgroundThe 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).ObjectiveThe 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.MethodsAβ pathology was determined by PET imaging, utilizing ¹¹C-Pittsburgh Compound B, ¹⁸F-flutemetamol, or ¹⁸F-florbetapir, in 157 AIBL participants who also underwent CSF collection. Using an INNOTEST assay, cut-points were established (Aβ(1-42) >544 ng/L, T-tau <407 ng/L, and P-tau181P <78 ng/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.ResultsCSF 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 Aβ(1-42) 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.ConclusionsCSF Aβ(1-42) 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.

33 keywords...

hide…