# 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

[^{18}F]-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 [^{18}F]-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:- ERC, entorhinal cortex
- Anterior HP or AHP, anterior hippocampus
- Fusiform or FFG, fusiform gyrus
- Inferior temporal or ITG, inferior temporal gyrus
- Superior frontal or SFG, superior frontal gyrus
- Precuneus or PRCU, precuneus
- Superior parietal or SPG, superior parietal gyrus
- Calcarine or CAL, calcarine
- 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