Association between tau deposition and antecedent amyloid-β accumulation rates in normal and early symptomatic individuals.
See Vandenberghe and Schaeverbeke (doi:10.1093/awx065) for a scientific commentary on this article. 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 18F-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 18F-AV-1451 binding and increased annualized change in cortical amyloid-β plaques measured as florbetapir positron emission tomography binding antecedent to 18F-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) 18F-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 18F-AV-1451 positron emission tomography scans, in the parieto-temporal and precuneus brain regions was associated with greater 18F-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 18F-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-β plaques correlate with cognition and clinical symptoms. Furthermore, non-local associations linking increased amyloid-β accumulation rates with increased tau deposition are of great interest and support the idea that the amyloid-β pathology might have remote effects in disease pathology spread potentially via the brain's intrinsic connectivity networks.
Department of Radiology and Biomedical Imaging, University of California - San Francisco, San Francisco, CA, USA.
Duygu
D
Tosun
Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA.
Susan
S
Landau
Department of Neurology, University of California-San Diego, San Diego, CA, USA.
Paul S
PS
Aisen
Department of Neurology, Mayo Clinic, Rochester MN, USA.
Ronald C
RC
Petersen
Avid Radiopharmaceuticals, Philadelphia, PA, USA.
Mark
M
Mintun
Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA.
William
W
Jagust
Department of Radiology and Biomedical Imaging, University of California - San Francisco, San Francisco, CA, USA.
Michael W
MW
Weiner
D000368:Aged; D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000378:metabolism*; D002243:Carbolines / Q000378:metabolism; D016022:Case-Control Studies; D003071:Cognition; D003430:Cross-Sectional Studies; D004522:Educational Status; D005026:Ethylene Glycols / Q000378:metabolism; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D058225:Plaque, Amyloid / Q000378:metabolism*; D049268:Positron-Emission Tomography; D012727:Sex Characteristics; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D001057:Apolipoproteins E; D002243:Carbolines; D005026:Ethylene Glycols; D016875:tau Proteins; C545186:florbetapir; C000591008:7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole
Alzheimer’s disease; amyloid-β; positron emission tomography; tau