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

Sci Transl Med. 2021 Jan 20;13(577):eabc0655. doi: 10.1126/scitranslmed.abc0655.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alzheimer Disease* / diagnostic imaging
  • Amyloid beta-Peptides
  • Humans
  • Positron-Emission Tomography
  • Tauopathies* / diagnostic imaging
  • tau Proteins


  • Amyloid beta-Peptides
  • tau Proteins