Longitudinal Assessment of Tau Pathology in Patients with Alzheimer's Disease Using [18F]THK-5117 Positron Emission Tomography

PLoS One. 2015 Oct 13;10(10):e0140311. doi: 10.1371/journal.pone.0140311. eCollection 2015.

Abstract

The formation of neurofibrillary tangles is believed to contribute to the neurodegeneration observed in Alzheimer's disease (AD). Postmortem studies have shown strong associations between the neurofibrillary pathology and both neuronal loss and the severity of cognitive impairment. However, the temporal changes in the neurofibrillary pathology and its association with the progression of the disease are not well understood. Tau positron emission tomography (PET) imaging is expected to be useful for the longitudinal assessment of neurofibrillary pathology in the living brain. Here, we performed a longitudinal PET study using the tau-selective PET tracer [18F]THK-5117 in patients with AD and in healthy control subjects. Annual changes in [18F]THK-5117 binding were significantly elevated in the middle and inferior temporal gyri and in the fusiform gyrus of patients with AD. Compared to patients with mild AD, patients with moderate AD showed greater changes in the tau load that were more widely distributed across the cortical regions. Furthermore, a significant correlation was observed between the annual changes in cognitive decline and regional [18F]THK-5117 binding. These results suggest that the cognitive decline observed in patients with AD is attributable to the progression of neurofibrillary pathology. Longitudinal assessment of tau pathology will contribute to the assessment of disease progression and treatment efficacy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / pathology*
  • Aniline Compounds*
  • Case-Control Studies
  • Demography
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Positron-Emission Tomography*
  • Quinolines*
  • tau Proteins / metabolism*

Substances

  • 6-((3-fluoro-2-hydroxy)propoxy)-2-(4-methylaminophenyl)quinoline
  • Aniline Compounds
  • Quinolines
  • tau Proteins

Grants and funding

This study was supported by research funds from GE Healthcare; the Sumitomo Electric Industries, Ltd., Group CSR Foundation; the Industrial Technology Research Grant Program of the NEDO in Japan (09E51025a); Health and Labor Sciences Research Grants from the Ministry of Health, Labor, and Welfare of Japan; a Grant-in-Aid for Scientific Research (B) (15H04900); a Grant-in-Aid for Scientific Research on Innovative Areas (Brain Protein Aging and Dementia Control) (26117003); a Grant-in-Aid for Young Scientists (B) (15K19767); and a Grant-in-Aid for JSPS Fellows and “Japan Advanced Molecular Imaging Program (J-AMP)” of the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.