PET Tau and Amyloid-β Burden in Mild Alzheimer's Disease: Divergent Relationship with Age, Cognition, and Cerebrospinal Fluid Biomarkers.
Deep and Frequent Phenotyping study team (,
Journal of Alzheimer's disease : JAD
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Koychev, I., Gunn, R. N., Firouzian, A., Lawson, J., Zamboni, G., Ridha, B., Sahakian, B., et al. (2017). PET Tau and Amyloid-β Burden in Mild Alzheimer's Disease: Divergent Relationship with Age, Cognition, and Cerebrospinal Fluid Biomarkers.. Journal of Alzheimer's disease : JAD, 60 (1), 283-293. https://doi.org/10.3233/jad-170129
BACKGROUND: Combining PET amyloid-β (Aβ) and tau imaging may be critical for tracking disease progression in Alzheimer's disease (AD). OBJECTIVE: We sought to characterize the relationship between Aβ and tau ligands as well as with other measures of pathology. METHODS: We conducted a multi-center observational study in early AD (MMSE >20) participants aged 50 to 85 y. The schedule included cognitive assessments (ADAS-Cog) and CSF measurement of Aβ and tau at baseline and 6 months; PET-CT imaging with Aβ ([18F]AV45) and tau ([18F]AV1451) ligands at baseline. RESULTS: 22 participants took part in the study with 20 completing its 6-month duration and 12 having both tau and amyloid PET. The PET biomarker analysis revealed a strong negative correlation between age and tau in multiple regions. Entorhinal cortex tau and age interacted significantly in terms of cognitive change over 6 months which may have been to older participants deteriorating faster despite lower levels of cortical tau. Cortical Aβ associated with entorhinal cortex tau while CSF tau/Aβ ratio correlated strongly with cortical tau but not Aβ. CONCLUSION: The negative relationship between age and cortical tau whereby younger patients with mild AD had relatively greater tau burden is potentially important. It suggests that younger-age onset AD may be primarily driven by tau pathology while AD developing later may depend on a multitude of pathological mechanisms. These data also suggest that PET-tau performs better than PET-amyloid in predicting the best validated AD diagnostic marker- the CSF total tau/Aβ ratio.
Deep and Frequent Phenotyping study team (, Humans, Alzheimer Disease, Ethylene Glycols, Aniline Compounds, Carbolines, tau Proteins, Positron-Emission Tomography, Analysis of Variance, Cognition Disorders, Psychiatric Status Rating Scales, Neuropsychological Tests, Aging, Aged, Female, Male, Amyloid beta-Peptides
WELLCOME TRUST (103838/Z/14/Z)
UNIVERSITY OF OXFORD (FB MRC) (MR/M024962/1)
Medical Research Council (MC_U105597119)
External DOI: https://doi.org/10.3233/jad-170129
This record's URL: https://www.repository.cam.ac.uk/handle/1810/270101