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Title: Alzheimer's Disease Normative Cerebrospinal Fluid Biomarkers Validated in PET Amyloid-β Characterized Subjects from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study.
Authors: Li, QX
Villmagne, VL
Doecke, JD
Rembach, A
Sarros, S
Varghese, S
McGlade, A
Laughton, KM
Pertile, KK
Fowler, CJ
Rumble, RL
Trounson, BO
Taddei, K
Rainey-Smith, SR
Laws, SM
Robertson, JS
Evered, LA
Silbert, B
Ellis, KA
Rowe, CC
Macaulay, SL
Darby, D
Martins, RN
Ames, D
Masters, CL
Collins, S
AIBL Research Group
Keywords: Alzheimer’s Disease
cerebrospinal fluid biomarkers
positron emission tomography Aβ imaging
cerebrospinal fluid
Positron-Emission Tomography
ROC curve
Mental Status Schedule
Issue Date: 2015
Source: 48(1):175-87
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 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. 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 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. CONCLUSIONS: CSF 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.
DOI: 10.3233/JAD-150247
PubMed URL:
Journal Title: Journal of Alzheimer's Disease
Type: Journal Article
Affiliates: Florey Institute of Neuroscience and Mental Health, The University of Melbourne
Department of Nuclear Medicine and Centre for PET, Austin Health
CSIRO Digital Productivity/Australian e-Health Research Centre and Cooperative Research Centre for Mental Health
Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical Sciences, Edith Cowan University
Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital)
Centre for Anaesthesia and Cognitive Function, Department of Anaesthesia, and Department of Surgery, St. Vincent's Hospital, The University of Melbourne
The University of Melbourne Academic Unit for Psychiatry of Old Age, St George's Hospital
CSIRO Food and Nutrition Flagship
School of Psychiatry and Clinical Neurosciences, University of Western Australia
National Ageing Research Institute
Department of Pathology, The University of Melbourne
Study/Trial: Case Control Studies
Appears in Collections:Scholarly and Clinical

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