Journal
EMBO MOLECULAR MEDICINE
Volume 8, Issue 10, Pages 1184-1196Publisher
WILEY
DOI: 10.15252/emmm.201606540
Keywords
Alzheimer's; biomarker; CSF; neurodegeneration
Categories
Funding
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
- National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering
- Canadian Institutes of Health Research
- Northern California Institute for Research and Education
- European Research Council
- Swedish Research Council
- Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University
- Swedish Brain Foundation
- Skane University Hospital Foundation
- Swedish Alzheimer Association
- Stiftelsen for Gamla Tjanarinnor
- Swedish federal government under the ALF Agreement
- Thelma Zoega Foundation
- Greta and Johan Kock Foundation
- Magnus Bergvwall Foundation
- Knut and Alice Wallenberg Foundation
- Torsten Soderberg Foundation
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Cerebrospinal fluid (CSF) tau (total tau, T-tau), neurofilament light (NFL), and neurogranin (Ng) are potential biomarkers for neurode-generation in Alzheimer's disease (AD). It is unknown whether these biomarkers provide similar or complementary information in AD. We examined 93 patients with AD, 187 patients with mild cognitive impairment, and 109 controls. T-tau, Ng, and NFL were all predictors of AD diagnosis. Combinations improved the diagnostic accuracy (AUC 85.5% for T-tau, Ng, and NFL) compared to individual biomarkers (T-tau 80.8%; Ng 71.4%; NFL 77.7%). T-tau and Ng were highly correlated (rho = 0.79, P < 0.001) and strongly associated with beta-amyloid (A beta) pathology, and with longitudinal deterioration in cognition and brain structure, primarily in people with A beta pathology. NFL on the other hand was not associated with A beta pathology and was associated with cognitive decline and brain atrophy independent of A beta. T-tau, Ng, and NFL provide partly independent information about neuronal injury and may be combined to improve the diagnostic accuracy for AD. T-tau and Ng reflect A beta-dependent neurodegeneration, while NFL reflects neurodegeneration independently of A beta pathology.
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