TY - JOUR
T1 - The cortical origin and initial spread of medial temporal tauopathy in Alzheimer's disease assessed with positron emission tomography
AU - Sanchez, J.S.
AU - Becker, J.A.
AU - Jacobs, H.I.L.
AU - Hanseeuw, B.J.
AU - Jiang, S.
AU - Schultz, A.P.
AU - Properzi, M.J.
AU - Katz, S.R.
AU - Beiser, A.
AU - Satizabal, C.L.
AU - O'Donnell, A.
AU - DeCarli, C.
AU - Killiany, R.
AU - El Fakhri, G.
AU - Normandin, M.D.
AU - Gomez-Isla, T.
AU - Quiroz, Y.T.
AU - Rentz, D.M.
AU - Sperling, R.A.
AU - Seshadri, S.
AU - Augustinack, J.
AU - Price, J.C.
AU - Johnson, K.A.
N1 - Funding Information:
This work was supported by NIH grants P01 AG036694 (to R.A.S. and K.A.J.), R01 AG046396 (to K.A.J.), P41 EB022544 (to G.E.F.), R01 AG049607 (to S.S.), R01 AG062559 (to H.I.L.J.), HHSN268201500001I and 75N92019D00031 (to S.S.), R01 AG061206 (to T.G.-I.), DP5OD019833 and R01 AG054671 (to Y.T.Q), and R01 AG050436, R01 DK112700, and R01 AG052414 (to J.C.P.).
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-beta (A beta) pathology to mediate neurodegeneration and cognitive decline. Initial TAU deposition occurs many years before A beta 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, A beta 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 A beta-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 A beta 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-beta (A beta) pathology to mediate neurodegeneration and cognitive decline. Initial TAU deposition occurs many years before A beta 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, A beta 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 A beta-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 A beta 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.
KW - age-related tauopathy
KW - autopsy cohort
KW - human cerebral-cortex
KW - human perirhinal cortex
KW - mild cognitive impairment
KW - national institute
KW - neurofibrillary tangles
KW - pathological process
KW - surface-based analysis
KW - tau pathology
KW - SURFACE-BASED ANALYSIS
KW - NEUROFIBRILLARY TANGLES
KW - AGE-RELATED TAUOPATHY
KW - MILD COGNITIVE IMPAIRMENT
KW - TAU PATHOLOGY
KW - PATHOLOGICAL PROCESS
KW - NATIONAL INSTITUTE
KW - HUMAN CEREBRAL-CORTEX
KW - HUMAN PERIRHINAL CORTEX
KW - AUTOPSY COHORT
U2 - 10.1126/scitranslmed.abc0655
DO - 10.1126/scitranslmed.abc0655
M3 - Article
C2 - 33472953
SN - 1946-6234
VL - 13
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 577
M1 - 0655
ER -