Normalization of CSF pTau measurement by Aβ40 improves its performance as a biomarker of Alzheimer’s disease

Guo, Tengfei; Korman, Deniz; La Joie, Renaud; Shaw, Leslie M.; Trojanowski, John Q.; Jagust, William J.; Landau, Susan M.

doi:10.1186/s13195-020-00665-8

Normalization of CSF pTau measurement by Aβ₄₀ improves its performance as a biomarker of Alzheimer’s disease

Journal Article · Sat Aug 15 00:00:00 EDT 2020 · Alzheimer's Research & Therapy

DOI:https://doi.org/10.1186/s13195-020-00665-8· OSTI ID:1815991

^[1]; Korman, Deniz ^[2]; La Joie, Renaud ^[3]; Shaw, Leslie M. ^[4]; Trojanowski, John Q. ^[4]; Jagust, William J. ^[5]; Landau, Susan M. ^[5]

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; OSTI
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
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

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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Contributing Organization:: Alzheimer’s Disease Neuroimaging Initiative

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1815991

Journal Information:: Alzheimer's Research & Therapy, Journal Name: Alzheimer's Research & Therapy Journal Issue: 1 Vol. 12; ISSN 1758-9193

Publisher:: BioMed CentralCopyright Statement

Country of Publication:: United States

Language:: English

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Additional file 1 of Normalization of CSF pTau measurement by Aβ40 improves its performance as a biomarker of Alzheimer’s disease Guo, Tengfei; Korman, Deniz; Joie, Renaud La https://doi.org/10.6084/m9.figshare.12813637 The current record is supplemented by this text	text	January 2020
Additional file 1 of Normalization of CSF pTau measurement by Aβ40 improves its performance as a biomarker of Alzheimer’s disease Guo, Tengfei; Korman, Deniz; Joie, Renaud La https://doi.org/10.6084/m9.figshare.12813637.v1 The current record is supplemented by this text	text	January 2020
Normalization of CSF pTau measurement by Aβ40 improves its performance as a biomarker of Alzheimer’s disease Guo, Tengfei; Korman, Deniz; Joie, Renaud La https://doi.org/10.6084/m9.figshare.c.5093218 The current record is supplemented by this collection	collection	January 2020
Normalization of CSF pTau measurement by Aβ40 improves its performance as a biomarker of Alzheimer’s disease Guo, Tengfei; Korman, Deniz; Joie, Renaud La https://doi.org/10.6084/m9.figshare.c.5093218.v1 The current record is supplemented by this collection	collection	January 2020

Normalization of CSF pTau measurement by Aβ40 improves its performance as a biomarker of Alzheimer’s disease

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Normalization of CSF pTau measurement by Aβ₄₀ improves its performance as a biomarker of Alzheimer’s disease