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PET Tau and Amyloid-β Burden in Mild Alzheimer's Disease: Divergent Relationship with Age, Cognition, and Cerebrospinal Fluid Biomarkers.

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Koychev, Ivan 
Gunn, Roger N 
Firouzian, Azadeh 
Lawson, Jennifer 
Zamboni, Giovanna 


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.



Alzheimer’s disease, amyloid beta-peptides, cerebrospinal fluid proteins, positron emission tomography, tau proteins, Aged, Aging, Alzheimer Disease, Amyloid beta-Peptides, Analysis of Variance, Aniline Compounds, Carbolines, Cognition Disorders, Ethylene Glycols, Female, Humans, Male, Neuropsychological Tests, Positron-Emission Tomography, Psychiatric Status Rating Scales, tau Proteins

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J Alzheimers Dis

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IOS Press
Wellcome Trust (103838/Z/14/Z)
Medical Research Council (MR/M024962/1)
Medical Research Council (MC_U105597119)
Medical Research Council (MC_UU_00005/12)
Medical Research Council (MR/L023784/2)
Medical Research Council (MR/L023784/1)