Abstract
Objective: To test whether plasma tau is altered in Alzheimer disease (AD) and whether it is related to changes in cognition, CSF biomarkers of AD pathology (including β-amyloid [Aβ] and tau), brain atrophy, and brain metabolism.
Methods: This was a study of plasma tau in prospectively followed patients with AD (n = 179), patients with mild cognitive impairment (n = 195), and cognitive healthy controls (n = 189) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and cross-sectionally studied patients with AD (n = 61), mild cognitive impairment (n = 212), and subjective cognitive decline (n = 174) and controls (n = 274) from the Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study at Lund University, Sweden. A total of 1284 participants were studied. Associations were tested between plasma tau and diagnosis, CSF biomarkers, MRI measures, 18fluorodeoxyglucose-PET, and cognition.
Results: Higher plasma tau was associated with AD dementia, higher CSF tau, and lower CSF Aβ42, but the correlations were weak and differed between ADNI and BioFINDER. Longitudinal analysis in ADNI showed significant associations between plasma tau and worse cognition, more atrophy, and more hypometabolism during follow-up.
Conclusions: Plasma tau partly reflects AD pathology, but the overlap between normal aging and AD is large, especially in patients without dementia. Despite group-level differences, these results do not support plasma tau as an AD biomarker in individual people. Future studies may test longitudinal plasma tau measurements in AD.
GLOSSARY
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- ADAS=
- Alzheimer's Disease Assessment Scale–Cognitive subscale;
- ADNI=
- Alzheimer's Disease Neuroimaging Initiative;
- BioFINDER=
- Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably;
- CI=
- confidence interval;
- CN=
- cognitively healthy control;
- DSM-III-R=
- Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition, Revised;
- EPIC=
- European Prospective Investigation Into Cancer and Nutrition;
- FDG=
- 18fluorodeoxyglucose;
- MCI=
- mild cognitive impairment;
- MMSE=
- Mini-Mental State Examination;
- P-tau=
- phosphorylated tau;
- T-tau=
- total tau
Footnotes
Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators is available at Neurology.org.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was paid by the authors.
Supplemental data at Neurology.org
- Received October 16, 2015.
- Accepted in final form July 12, 2016.
- © 2016 American Academy of Neurology
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