TY - JOUR
T1 - The cortical origin and initial spread of medial temporal tauopathy in Alzheimer's disease assessed with positron emission tomography
AU - Sanchez, Justin S.
AU - Becker, J. Alex
AU - Jacobs, Heidi I.L.
AU - Hanseeuw, Bernard J.
AU - Jiang, Shu
AU - Schultz, Aaron P.
AU - Properzi, Michael J.
AU - Katz, Samantha R.
AU - Beiser, Alexa
AU - Satizabal, Claudia L.
AU - O'Donnell, Adrienne
AU - DeCarli, Charles
AU - Killiany, Ron
AU - El Fakhri, Georges
AU - Normandin, Marc D.
AU - Gómez-Isla, Teresa
AU - Quiroz, Yakeel T.
AU - Rentz, Dorene M.
AU - Sperling, Reisa A.
AU - Seshadri, Sudha
AU - Augustinack, Jean
AU - Price, Julie C.
AU - Johnson, Keith A.
N1 - Publisher Copyright:
Copyright © 2021 The Authors.
PY - 2021/1/20
Y1 - 2021/1/20
N2 - Advances in molecular positron emission tomography (PET) have enabled anatomic tracking of brain pathology in longitudinal studies of normal aging and dementia, including assessment of the central model of Alzheimer's disease (AD) pathogenesis, according to which TAU pathology begins focally but expands catastrophically under the influence of amyloid-β (Aβ) pathology to mediate neurodegeneration and cognitive decline. Initial TAU deposition occurs many years before Aβ in a specific area of the medial temporal lobe. Building on recent work that enabled focus of molecular PET measurements on specific TAU-vulnerable convolutional temporal lobe anatomy, we applied an automated anatomic sampling method to quantify TAU PET signal in 443 adult participants from several observational studies of aging and AD, spanning a wide range of ages, Aβ burdens, and degrees of clinical impairment. We detected initial cortical emergence of tauopathy near the rhinal sulcus in clinically normal people and, in a subset with longitudinal 2-year follow-up data (n = 104), tracked Aβ-associated spread of TAU from this site first to nearby neocortex of the temporal lobe and then to extratemporal regions. Greater rate of TAU spread was associated with baseline measures of both global Aβ burden and medial temporal lobe TAU. These findings are consistent with clinicopathological correlation studies of Alzheimer's tauopathy and enable precise tracking of AD-related TAU progression for natural history studies and prevention therapeutic trials.
AB - Advances in molecular positron emission tomography (PET) have enabled anatomic tracking of brain pathology in longitudinal studies of normal aging and dementia, including assessment of the central model of Alzheimer's disease (AD) pathogenesis, according to which TAU pathology begins focally but expands catastrophically under the influence of amyloid-β (Aβ) pathology to mediate neurodegeneration and cognitive decline. Initial TAU deposition occurs many years before Aβ in a specific area of the medial temporal lobe. Building on recent work that enabled focus of molecular PET measurements on specific TAU-vulnerable convolutional temporal lobe anatomy, we applied an automated anatomic sampling method to quantify TAU PET signal in 443 adult participants from several observational studies of aging and AD, spanning a wide range of ages, Aβ burdens, and degrees of clinical impairment. We detected initial cortical emergence of tauopathy near the rhinal sulcus in clinically normal people and, in a subset with longitudinal 2-year follow-up data (n = 104), tracked Aβ-associated spread of TAU from this site first to nearby neocortex of the temporal lobe and then to extratemporal regions. Greater rate of TAU spread was associated with baseline measures of both global Aβ burden and medial temporal lobe TAU. These findings are consistent with clinicopathological correlation studies of Alzheimer's tauopathy and enable precise tracking of AD-related TAU progression for natural history studies and prevention therapeutic trials.
UR - https://www.scopus.com/pages/publications/85099451255
U2 - 10.1126/scitranslmed.abc0655
DO - 10.1126/scitranslmed.abc0655
M3 - Article
C2 - 33472953
AN - SCOPUS:85099451255
SN - 1946-6234
VL - 13
JO - Science translational medicine
JF - Science translational medicine
IS - 577
M1 - eabc0655
ER -