Association between tau deposition and antecedent amyloid-beta accumulation rates in normal and early symptomatic individuals

作者：Tosun Duygu; Landau Susan; Aisen Paul S; Petersen Ronald C; Mintun Mark; Jagust William; Weiner Michael W

来源：Brain, 2017, 140(5): 1499-1512.

DOI：10.1093/brain/awx046

• amyloid-beta
• tau
• positron emission tomography
• Alzheimer's disease

A long-term goal of our field is to determine the sequence of pathological events, which ultimately lead to cognitive decline and dementia. In this study, we first assessed the patterns of brain tau tangle accumulation (measured with the positron emission tomography tracer F-18-AV-1451) associated with well-established Alzheimer's disease factors in a cohort including cognitively healthy elderly individuals and individuals at early symptomatic stages of Alzheimer's disease. We then explored highly associated patterns of greater F-18-AV-1451 binding and increased annualized change in cortical amyloid-beta plaques measured as florbetapir positron emission tomography binding antecedent to F-18-AV-1451 positron emission tomography scans, and to what extent these multimodal pattern associations explained the variance in cognitive performance and clinical outcome measures, independently and jointly. We found that: (i) F-18-AV-1451 positron emission tomography retention was differentially associated with age, and cross-sectional florbetapir positron emission tomography retention, but not with years of education, gender, or APOE genotype; (ii) increased annualized change in florbetapir retention, antecedent to F-18-AV-1451 positron emission tomography scans, in the parieto-temporal and precuneus brain regions was associated with greater F-18-AV-1451 PET retention most prominently in the inferior temporal and inferior parietal regions in the full cohort, with florbetapir positive/negative-associated variability; and (iii) this F-18-AV-1451 positron emission tomography retention pattern significantly explained the variance in cognitive performance and clinical outcome measures, independent of the associated antecedent increased annualized change in florbetapir positron emission tomography retention. These findings are in agreement with the pathology literature, which suggests that tau tangles but not amyloid-beta plaques correlate with cognition and clinical symptoms. Furthermore, non-local associations linking increased amyloid-beta accumulation rates with increased tau deposition are of great interest and support the idea that the amyloid-beta pathology might have remote effects in disease pathology spread potentially via the brain's intrinsic connectivity networks.

• 出版日期2017-5