The cortical origin and initial spread of medial temporal tauopathy in Alzheimer's disease assessed with positron emission tomography

J.S. Sanchez*, J.A. Becker, H.I.L. Jacobs, B.J. Hanseeuw, S. Jiang, A.P. Schultz, M.J. Properzi, S.R. Katz, A. Beiser, C.L. Satizabal, A. O'Donnell, C. DeCarli, R. Killiany, G. El Fakhri, M.D. Normandin, T. Gomez-Isla, Y.T. Quiroz, D.M. Rentz, R.A. Sperling, S. SeshadriJ. Augustinack, J.C. Price, K.A. Johnson*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

52 Citations (Web of Science)

Abstract

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.
Original languageEnglish
Article number0655
Number of pages12
JournalScience Translational Medicine
Volume13
Issue number577
DOIs
Publication statusPublished - 20 Jan 2021

Keywords

  • age-related tauopathy
  • autopsy cohort
  • human cerebral-cortex
  • human perirhinal cortex
  • mild cognitive impairment
  • national institute
  • neurofibrillary tangles
  • pathological process
  • surface-based analysis
  • tau pathology
  • SURFACE-BASED ANALYSIS
  • NEUROFIBRILLARY TANGLES
  • AGE-RELATED TAUOPATHY
  • MILD COGNITIVE IMPAIRMENT
  • TAU PATHOLOGY
  • PATHOLOGICAL PROCESS
  • NATIONAL INSTITUTE
  • HUMAN CEREBRAL-CORTEX
  • HUMAN PERIRHINAL CORTEX
  • AUTOPSY COHORT

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