Patterns of tau pathology identified with 18 F-MK-6240 PET imaging

Alzheimers Dement. 2022 Feb;18(2):272-282. doi: 10.1002/alz.12384. Epub 2021 May 31.

Abstract

Introduction: Positron emission tomography (PET) imaging for neurofibrillary tau allows investigation of the in vivo spatiotemporal progression of Alzheimer's disease (AD) pathology. We evaluated the suitability of 18 F-MK-6240 in a clinical sample and determined the relationships among 18 F-MK-6240 binding, age, cognition, and cerebrospinal fluid (CSF)-based AD biomarkers.

Methods: Participants (n = 101, 72 ± 9 years, 52% women) underwent amyloid PET, tau PET, structural T1-weighted magnetic resonance imaging, and neuropsychological evaluation. Twenty-one participants had lumbar puncture for CSF measurement of amyloid beta (Aβ)42 , tau, and phosphorylated tau (p-tau).

Results: 18 F-MK-6240 recapitulated Braak staging and correlated with CSF tau and p-tau, normalized to Aβ42 . 18 F-MK-6240 negatively correlated with age across Braak regions in amyloid-positive participants, consistent with greater tau pathology in earlier onset AD. Domain-specific, regional patterns of 18 F-MK-6240 binding were associated with reduced memory, executive, and language performance, but only in amyloid-positive participants.

Discussion: 18 F-MK-6240 can approximate Braak staging across the AD continuum and provide region-dependent insights into biomarker-based AD models.

Keywords: Alzheimer's disease; MK-6240; amyloid positivity; cerebrospinal fluid; cognition; tau positivity; tau positron emission tomography.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides / metabolism
  • Biomarkers
  • Cognitive Dysfunction* / diagnostic imaging
  • Cognitive Dysfunction* / metabolism
  • Female
  • Humans
  • Isoquinolines / metabolism
  • Male
  • Middle Aged
  • Positron-Emission Tomography / methods
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Isoquinolines
  • MK-6240
  • tau Proteins