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Data from: Flortaucipir PET uncovers relationships between tau and β-amyloid in aging, primary age related tauopathy, and Alzheimer disease

Cite this dataset

Josephs, Keith et al. (2024). Data from: Flortaucipir PET uncovers relationships between tau and β-amyloid in aging, primary age related tauopathy, and Alzheimer disease [Dataset]. Dryad. https://doi.org/10.5061/dryad.v6wwpzh48

Abstract

[18F]-Flortaucipir PET is considered a good biomarker of Alzheimer’s disease. However, it is unknown how flortaucipir is associated with the distribution of tau across brain regions and how these associations are influenced by β-amyloid. It is also unclear whether flortaucipir can detect tau in definite primary age-related tauopathy (PART). We identified 248 individuals at Mayo Clinic that had undergone [18F]-flortaucipir PET during life, had died, and undergone an autopsy, 239 cases of which also had β-amyloid PET. We assessed nonlinear relationships between flortaucipir uptake in nine medial temporal and cortical regions, Braak tau stage and Thal β-amyloid phase using generalized additive models. We found that flortaucipir uptake was greater with increasing tau stage in all regions. Increased uptake at low tau stages in medial temporal regions was only observed in cases with high β-amyloid phase. Flortaucipir uptake linearly increased with β-amyloid phase in medial temporal and cortical regions. The highest flortaucipir uptake occurred with high Alzheimer’s disease neuropathologic change (ADNC) scores, followed by low-intermediate ADNC scores, then PART, with entorhinal cortex providing the best differentiation between groups. Flortaucipir PET had limited ability to detect PART and imaging defined PART did not correspond with pathologically defined PART. In summary, spatial patterns of flortaucipir mirrored histopathological tau distribution, were influenced by β-amyloid phase, and were useful for distinguishing different ADNC scores and PART.

README: Data sets for "Flortaucipir PET uncovers relationships between tau and β-amyloid in aging, primary age related tauopathy, and Alzheimer disease"

Each of these file corresponds to a figure in the main paper or in the supplementary materials.

figure1.csv

  • Thal is Thal phase which is measured by histopathology. This is an ordinal variable with no units.
  • Braak is Braak neurofibrillary tangle stage. This is an ordinal variable with no units. Braak stages are sometimes styled using Roman numerals.
  • Group is a composite variable representing how we combined Thal phase and Braak stage.

figure2.csv

  • region is the location in the brain where the flortaucipir PET tracer was measured. The regions are as follows:
    1. ERC, entorhinal cortex
    2. Anterior HP or AHP, anterior hippocampus
    3. Fusiform or FFG, fusiform gyrus
    4. Inferior temporal or ITG, inferior temporal gyrus
    5. Superior frontal or SFG, superior frontal gyrus
    6. Precuneus or PRCU, precuneus
    7. Superior parietal or SPG, superior parietal gyrus
    8. Calcarine or CAL, calcarine
    9. Precentral or PrCG, precentral gyrus
  • thal is the Thal phase as in figure1.csv.
  • braak is the Braak stage as in figure1.csv.
  • estimates corresponds to the model-based estimated geometric mean standardized uptake value ratio (SUVR) from the generalized additive model. This variable is a ratio and unitless although some researchers use the phrase "SUVR units."

figure3.csv and figure3_labels.csv1

This figure can be thought of as a 6 Thal phases (rows) by 7 Braak
stages (columns) grid and within each "cell" is a 3x3 sub array
corresponding to the 9 regions. The estimates for the figure are in a
(6 * 3) x (7 * 3) = 18 x 21 matrix found in figure3.csv. They are scaled
to the unit interval.

The file figure3_labels.csv gives the coordinates for the region
labels.

  • position_x_axis is the position on the x-axis in terms of the unit interval.
  • position_y_axis is the position on the y-axis in terms of the unit interval.
  • roi is the region of interest, or simply region, label. The regions here are abbreviated. See above for the mapping between abbreviation and region of interest.

figure4.csv

  • erc_tau is the entorhinal cortex flortaucipir SUVR value for each individual in the study and is plotted in panel B.
  • group is the four-level composite group used throughout the paper.
  • braak is the Braak stage as in figure1.csv.
  • thal is the Thal phase as in figure1.csv.
  • cerad stands for "Consortium to Establish a Registry for Alzheimer’s Disease (CERAD)" and is an ordinal neuropathology variable.
  • pib is the Pittsburgh Compound B (PiB) group. PiB is the amyloid PET ligand used in this study. The label "PiB +" corresponds to an elevated (abnormal) PiB SUVR, "PiB -" corresponds to a normal PiB SUVR, and "No PiB" means the participant did not have a PiB scan.

figureS1.csv

  • region is the 9-level region or region of interest (ROI) as in figure2.csv.
  • position_x_axis is the position on the x-axis for plotting.
  • contrast is an ordinal variable which indicates which Braak stages are being contrasted (or differenced).
  • estimates is the estimate for the contrast, or the estimated percentage difference based on the generalized additive models summarized in Figure 2.
  • lcl corresponds to the lower 95% confidence limit.
  • ucl corresponds to the upper 95% confidence limit.

figureS2_S4.csv

The data for Figure S2 and S4 are the same and can be thought of as a
variation of Figure 2 but using partial volume correction (PVC) to
account for atrophy. Figure S2 has Braak stage on the x-axis and lines
for Thal phase while Figure S4 has Thal phase on the x-axis with lines
for Braak stage.

  • region is the 9-level region or region of interest (ROI) as in figure2.csv.
  • thal is the Thal phase as in figure1.csv.
  • braak is the Braak stage as in figure1.csv.
  • estimates corresponds to the model-based estimated geometric mean standardized uptake value ratio (SUVR) from the generalized additive model fit to PVC data.

figureS3.csv

This figure is similar to Figure S1 but here Thal phases are being
contrast.

  • region is the 9-level region or region of interest (ROI) as in figure2.csv.
  • position_x_axis is the position on the x-axis for plotting.
  • contrast is an ordinal variable which indicates which Thal phases are being contrasted (or differenced).
  • estimates is the estimate for the contrast, or the estimated percentage difference in means based on the generalized additive models summarized in Figure 2.
  • lcl corresponds to the lower 95% confidence limit.
  • ucl corresponds to the upper 95% confidence limit.

figureS5.csv

This figure gives the estimated mean SUVR for combinations
of Braak stage and Thal phase for six different model fits.

  • model is the model being fit. This is a categorical variable with six levels.
  • region is the 9-level region or region of interest (ROI) as in figure2.csv.
  • position_y_axis is the y-axis position for plotting. It corresponds to the Thal phase with jittering.
  • braak is the Braak stage as in figure1.csv.
  • estimates is the estimated geometric mean flortaucipir SUVR for the Braak-Thal combination for a particular model.
  • lcl corresponds to the lower 95% confidence limit.
  • ucl corresponds to the upper 95% confidence limit.

figureS6.csv

  • region is the 9-level region or region of interest (ROI) as in figure2.csv.
  • group is an eight-level grouping variable indicating the person-level group.
  • taupet is the within-region, person-level flortaucipir PET SUVR value.

figureS7.csv

  • position_x_axis gives the position on the x-axis (the Braak axis) for the point plotted.
  • position_y_axis gives the position on the y-axis (the Thal axis) for the point plotted.
  • erc_group is the entorhinal cortex (ERC) SUVR group.
  • number_subjects is the number of participants for the given combination of Thal, Braak, CERAD, and PiB. (For CERAD and PiB, see figure4.csv.)
  • cerad as in figure4.csv.
  • pib as in figure4.csv.

figureS8.csv

  • thal is the Thal phase as in figure1.csv.
  • centiloid is the amyloid PET centiloid value. This is a rescaling of PiB whereby 0 represents the mean SUVR value for a reference group of controls and 100 represents the mean SUVR value for a reference group of individuals with Alzheimer's. Note that values below 0 and above 100 are possible.
  • cerad as in figure4.csv.
  • group is the four-level composite group used throughout the paper.

Methods

These data are from 248 participants recruited from Mayo Clinic, Rochester, MN, who had flortaucipir PET imaging during life, had died, and had undergone an autopsy evaluation. All patients were enrolled into one of three NIH funded cohort studies including the Mayo Clinic Alzheimer’s Disease Research Center (PI: Petersen), The Mayo Clinic Study of Aging (PI: Petersen) and the Neurodegenerative Research Group (PIs: Josephs/Whitwell).

Funding

National Institute on Aging, Award: RF1-NS112153

National Institute on Aging, Award: R01-AG50603

National Institute on Aging, Award: R01-AG37491

National Institute on Aging, Award: R01-DC12519

National Institute on Aging, Award: R01-DC14942

National Institute on Aging, Award: R01-NS89757

National Institute on Aging, Award: R37-AG11378

National Institute on Aging, Award: P30-AG062677

National Institute on Aging, Award: U01-AG 006786