Normalization of CSF pTau measurement by Aβ40 improves its performance as a biomarker of Alzheimer’s disease
Abstract
Alzheimer’s disease (AD)-related tauopathy can be measured with CSF phosphorylated tau (pTau) and tau PET. We aim to investigate the associations between these measurements and their relative ability to predict subsequent disease progression. In 219 cognitively unimpaired and 122 impaired Alzheimer’s Disease Neuroimaging Initiative participants with concurrent amyloid-β (Aβ) PET (18F-florbetapir or 18F-florbetaben), 18F-flortaucipir (FTP) PET, CSF measurements, structural MRI, and cognition, we examined inter-relationships between these biomarkers and their predictions of subsequent FTP and cognition changes. The use of a CSF pTau/Aβ40 ratio eliminated positive associations we observed between CSF pTau alone and CSF Aβ42 in the normal Aβ range likely reflecting individual differences in CSF production rather than pathology. Use of the CSF pTau/Aβ40 ratio also increased expected associations with Aβ PET, FTP PET, hippocampal volume, and cognitive decline compared to pTau alone. In Aβ+ individuals, abnormal CSF pTau/Aβ40 only individuals (26.7%) were 4 times more prevalent (p < 0.001) than abnormal FTP only individuals (6.8%). Furthermore, among individuals on the AD pathway, CSF pTau/Aβ40 mediates the association between Aβ PET and FTP PET accumulation, but FTP PET is more closely linked to subsequent cognitive decline than CSF pTau/Aβ40. Together, these findings suggest that CSF pTau/Aβ40 may bemore »
- Authors:
-
[1];
- Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging
- Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.
- Univ. of California, San Francisco, CA (United States). Dept. of Neurology. Memory & Aging Center
- Univ. of Pennsylvania, Philadelphia, PA (United States). Perelman School of Medicine. Dept. of Pathology. Lab. Medicine
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- Contributing Org.:
- Alzheimer’s Disease Neuroimaging Initiative
- OSTI Identifier:
- 1815991
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Alzheimer's Research & Therapy
- Additional Journal Information:
- Journal Volume: 12; Journal Issue: 1; Journal ID: ISSN 1758-9193
- Publisher:
- BioMed Central
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; Tau; CSF pTau/Aβ40; PET; Cognition; Alzheimer’s disease
Citation Formats
Guo, Tengfei, Korman, Deniz, La Joie, Renaud, Shaw, Leslie M., Trojanowski, John Q., Jagust, William J., and Landau, Susan M. Normalization of CSF pTau measurement by Aβ40 improves its performance as a biomarker of Alzheimer’s disease. United States: N. p., 2020.
Web. doi:10.1186/s13195-020-00665-8.
Guo, Tengfei, Korman, Deniz, La Joie, Renaud, Shaw, Leslie M., Trojanowski, John Q., Jagust, William J., & Landau, Susan M. Normalization of CSF pTau measurement by Aβ40 improves its performance as a biomarker of Alzheimer’s disease. United States. https://doi.org/10.1186/s13195-020-00665-8
Guo, Tengfei, Korman, Deniz, La Joie, Renaud, Shaw, Leslie M., Trojanowski, John Q., Jagust, William J., and Landau, Susan M. Sat .
"Normalization of CSF pTau measurement by Aβ40 improves its performance as a biomarker of Alzheimer’s disease". United States. https://doi.org/10.1186/s13195-020-00665-8. https://www.osti.gov/servlets/purl/1815991.
@article{osti_1815991,
title = {Normalization of CSF pTau measurement by Aβ40 improves its performance as a biomarker of Alzheimer’s disease},
author = {Guo, Tengfei and Korman, Deniz and La Joie, Renaud and Shaw, Leslie M. and Trojanowski, John Q. and Jagust, William J. and Landau, Susan M.},
abstractNote = {Alzheimer’s disease (AD)-related tauopathy can be measured with CSF phosphorylated tau (pTau) and tau PET. We aim to investigate the associations between these measurements and their relative ability to predict subsequent disease progression. In 219 cognitively unimpaired and 122 impaired Alzheimer’s Disease Neuroimaging Initiative participants with concurrent amyloid-β (Aβ) PET (18F-florbetapir or 18F-florbetaben), 18F-flortaucipir (FTP) PET, CSF measurements, structural MRI, and cognition, we examined inter-relationships between these biomarkers and their predictions of subsequent FTP and cognition changes. The use of a CSF pTau/Aβ40 ratio eliminated positive associations we observed between CSF pTau alone and CSF Aβ42 in the normal Aβ range likely reflecting individual differences in CSF production rather than pathology. Use of the CSF pTau/Aβ40 ratio also increased expected associations with Aβ PET, FTP PET, hippocampal volume, and cognitive decline compared to pTau alone. In Aβ+ individuals, abnormal CSF pTau/Aβ40 only individuals (26.7%) were 4 times more prevalent (p < 0.001) than abnormal FTP only individuals (6.8%). Furthermore, among individuals on the AD pathway, CSF pTau/Aβ40 mediates the association between Aβ PET and FTP PET accumulation, but FTP PET is more closely linked to subsequent cognitive decline than CSF pTau/Aβ40. Together, these findings suggest that CSF pTau/Aβ40 may be a superior measure of tauopathy compared to CSF pTau alone, and CSF pTau/Aβ40 enables detection of tau accumulation at an earlier stage than FTP among Aβ+ individuals.},
doi = {10.1186/s13195-020-00665-8},
journal = {Alzheimer's Research & Therapy},
number = 1,
volume = 12,
place = {United States},
year = {Sat Aug 15 00:00:00 EDT 2020},
month = {Sat Aug 15 00:00:00 EDT 2020}
}
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