Amyloid and tau PET demonstrate region-specific associations in normal older people

Neuroimage. 2017 Apr 15;150:191-199. doi: 10.1016/j.neuroimage.2017.02.051. Epub 2017 Feb 21.

Abstract

β-amyloid (Aβ) and tau pathology become increasingly prevalent with age, however, the spatial relationship between the two pathologies remains unknown. We examined local (same region) and non-local (different region) associations between these 2 aggregated proteins in 46 normal older adults using [18F]AV-1451 (for tau) and [11C]PiB (for Aβ) positron emission tomography (PET) and 1.5T magnetic resonance imaging (MRI) images. While local voxelwise analyses showed associations between PiB and AV-1451 tracer largely in the temporal lobes, k-means clustering revealed that some of these associations were driven by regions with low tracer retention. We followed this up with a whole-brain region-by-region (local and non-local) partial correlational analysis. We calculated each participant's mean AV-1451 and PiB uptake values within 87 regions of interest (ROI). Pairwise ROI analysis demonstrated many positive PiB-AV-1451 associations. Importantly, strong positive partial correlations (controlling for age, sex, and global gray matter fraction, p<.01) were identified between PiB in multiple regions of association cortex and AV-1451 in temporal cortical ROIs. There were also less frequent and weaker positive associations of regional PiB with frontoparietal AV-1451 uptake. Particularly in temporal lobe ROIs, AV-1451 uptake was strongly predicted by PiB across multiple ROI locations. These data indicate that Aβ and tau pathology show significant local and non-local regional associations among cognitively normal elderly, with increased PiB uptake throughout the cortex correlating with increased temporal lobe AV-1451 uptake. The spatial relationship between Aβ and tau accumulation does not appear to be specific to Aβ location, suggesting a regional vulnerability of temporal brain regions to tau accumulation regardless of where Aβ accumulates.

Keywords: Aging; Alzheimer's disease; Amyloid; PET; Polypathology; Tau.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / pathology*
  • Amyloid beta-Peptides / analysis
  • Amyloid beta-Peptides / metabolism*
  • Aniline Compounds
  • Carbolines
  • Carbon Radioisotopes
  • Female
  • Humans
  • Image Interpretation, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Positron-Emission Tomography
  • Radiopharmaceuticals
  • Temporal Lobe / pathology*
  • Thiazoles
  • tau Proteins / analysis
  • tau Proteins / metabolism*

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Carbolines
  • Carbon Radioisotopes
  • Radiopharmaceuticals
  • Thiazoles
  • tau Proteins
  • 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole