Mesial temporal tau is related to worse cognitive performance and greater neocortical tau load in amyloid-β-negative cognitively normal individuals

Neurobiol Aging. 2021 Jan:97:41-48. doi: 10.1016/j.neurobiolaging.2020.09.017. Epub 2020 Oct 1.

Abstract

We examined whether mesial temporal (Me) tau relates to cognitive performance in 47 amyloid-β (Aβ)-negative, cognitively normal older adults (>60 years old). Me-tau was measured using [18F]flortaucipir-positron emission tomography standardized uptake value ratio. The effect of continuous and categorical (stratified at standardized uptake value ratio = 1.2 [21% Me-positive]) Me-tau on cognition (mini-mental state examination, pre-Alzheimer's cognitive composite, a memory composite, and a nonmemory composite score) was examined using general linear models, and associations between Me-tau and [18F]flortaucipir signal in the neocortex were assessed using voxelwise regressions (continuous) and voxelwise contrasts (categorical). In addition, we assessed the effect of age and Aβ burden on Me-tau. Both continuous and categorical Me-tau was associated with worse cognitive performance across all tests and with higher lateral temporal and parietal [18F]flortaucipir signal. Furthermore, we observed a marginal association between Me-tau and age, whereas there was no association with Aβ burden. Our findings indicate that Me-tau in Aβ-negative cognitively normal individuals, which is likely age-related (i.e., primary age-related tauopathy), might not be as benign as commonly thought.

Keywords: Mesial temporal lobe; PART; PET; Tau.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / metabolism*
  • Aging / psychology*
  • Amyloid beta-Peptides / metabolism
  • Carbolines
  • Cognition / physiology*
  • Female
  • Humans
  • Male
  • Mental Status and Dementia Tests
  • Neocortex / metabolism*
  • Positron-Emission Tomography
  • Radiopharmaceuticals
  • tau Proteins / metabolism*

Substances

  • Amyloid beta-Peptides
  • Carbolines
  • Radiopharmaceuticals
  • tau Proteins
  • 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole