| Autor: |
Josephs, Keith A., Tosakulwong, Nirubol, Weigand, Stephen D., Graff-Radford, Jonathan, Schwarz, Christopher G., Senjem, Matthew L., Machulda, Mary M., Kantarci, Kejal, Knopman, David S., Nguyen, Aivi, Reichard, R. Ross, Dickson, Dennis W., Petersen, Ronald C., Lowe, Val J., Jack Jr., Clifford R., Whitwell, Jennifer L. |
| Předmět: |
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| Zdroj: |
Science Translational Medicine; 7/24/2024, Vol. 16 Issue 757, p1-15, 15p |
| Abstrakt: |
[18F]-Flortaucipir positron emission tomography (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 amyloid-β. It is also unclear whether flortaucipir can detect tau in definite primary age–related tauopathy (PART). We identified 248 individuals at Mayo Clinic who had undergone [18F]-flortaucipir PET during life, had died, and had undergone an autopsy, 239 cases of which also had amyloid-β PET. We assessed nonlinear relationships between flortaucipir uptake in nine medial temporal and cortical regions, Braak tau stage, and Thal amyloid-β 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 a high amyloid-β phase. Flortaucipir uptake linearly increased with the amyloid-β 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 the 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 the histopathological tau distribution, were influenced by the amyloid-β phase, and were useful for distinguishing different ADNC scores and PART. Editor's summary: [18F]-Flortaucipir positron emission tomography (tau PET) is a noninvasive method to detect tau depositions in the brain of patients with tauopathies, including Alzheimer's disease (AD). How tau PET measurements relate to histologically confirmed distributions of tau and amyloid-β is not completely understood. Josephs et al. performed antemortem tau PET versus autopsy comparisons and found nonlinear positive relationships among tau distribution, amyloid-β, and tau PET. Tau PET could differentiate between stages of AD neuropathologic changes but could not detect tau deposition in primary age–related tauopathy. These findings provide a promising resource for the interpretation of tau PET studies. —Daniela Neuhofer [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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