TY - JOUR
T1 - Widespread distribution of tauopathy in preclinical Alzheimer's disease
AU - Schultz, Stephanie A.
AU - Gordon, Brian A.
AU - Mishra, Shruti
AU - Su, Yi
AU - Perrin, Richard J.
AU - Cairns, Nigel J.
AU - Morris, John C.
AU - Ances, Beau M.
AU - Benzinger, Tammie L.S.
N1 - Funding Information:
The authors acknowledge the financial support of Fred Simmons and Olga Mohan, the Charles F. and Joanne Knight Alzheimer's Research Initiative, the Hope Center for Neurological Disorders, the Mallinckrodt Institute of Radiology, the American Society for Neuroradiology, and the Barnes-Jewish Hospital Foundation (BJHF), the BJHF Paula and Rodger Riney Fund, and the BJHF Willman Scholar Fund. This research was additionally funded by the National Institutes of Health grants P50AG005681 , P01AG026276 , P01AG003991 , R01AG043434 , UL1TR000448 , R01EB009352 , 1P30NS098577 , and K01AG053474-01A1 . Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly) provided doses of 18 F-florbetapir, partial funding for 18 F-florbetapir scanning, precursor for 18 F-flortaucipir, and technology transfer for manufacturing of 18 F-flortaucipir. The authors thank their participants, without whom this study would not have been possible.
Publisher Copyright:
© 2018
PY - 2018/12
Y1 - 2018/12
N2 - The objective of this study was to examine the distribution and severity of tau-PET binding in cognitively normal adults with preclinical Alzheimer's disease as determined by positive beta-amyloid PET. 18F-AV-1451 tau-PET data from 109 cognitively normal older adults were processed with 34 cortical and 9 subcortical FreeSurfer regions and averaged across both hemispheres. Individuals were classified as being beta-amyloid positive (N = 25, A+) or negative (N = 84, A−) based on a 18F-AV-45 beta-amyloid-PET standardized uptake value ratio of 1.22. We compared the tau-PET binding in the 2 groups using covariate-adjusted linear regressions. The A+ cohort had higher tau-PET binding within 8 regions: precuneus, amygdala, banks of the superior temporal sulcus, entorhinal cortex, fusiform gyrus, inferior parietal cortex, inferior temporal cortex, and middle temporal cortex. These findings, consistent with preclinical involvement of the medial temporal lobe and parietal lobe and association regions by tauopathy, emphasize that therapies targeting tauopathy in Alzheimer's disease could be considered before the onset of symptoms to prevent or ameliorate cognitive decline.
AB - The objective of this study was to examine the distribution and severity of tau-PET binding in cognitively normal adults with preclinical Alzheimer's disease as determined by positive beta-amyloid PET. 18F-AV-1451 tau-PET data from 109 cognitively normal older adults were processed with 34 cortical and 9 subcortical FreeSurfer regions and averaged across both hemispheres. Individuals were classified as being beta-amyloid positive (N = 25, A+) or negative (N = 84, A−) based on a 18F-AV-45 beta-amyloid-PET standardized uptake value ratio of 1.22. We compared the tau-PET binding in the 2 groups using covariate-adjusted linear regressions. The A+ cohort had higher tau-PET binding within 8 regions: precuneus, amygdala, banks of the superior temporal sulcus, entorhinal cortex, fusiform gyrus, inferior parietal cortex, inferior temporal cortex, and middle temporal cortex. These findings, consistent with preclinical involvement of the medial temporal lobe and parietal lobe and association regions by tauopathy, emphasize that therapies targeting tauopathy in Alzheimer's disease could be considered before the onset of symptoms to prevent or ameliorate cognitive decline.
KW - Alzheimer's disease
KW - Parietal lobe
KW - Positron emission tomography
KW - Tau
KW - Temporal lobe
UR - http://www.scopus.com/inward/record.url?scp=85054206549&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2018.08.022
DO - 10.1016/j.neurobiolaging.2018.08.022
M3 - Article
C2 - 30292840
AN - SCOPUS:85054206549
SN - 0197-4580
VL - 72
SP - 177
EP - 185
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -