HAI Book 2025 - Flipbook - Page 602
Saha, Pampa
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Association of plasma GFAP with tau PET in cognitively unimpaired
Aβ-negative subjects
Pampa Saha1, Bruna Bellaver1, Guilherme Povala1, Pamela C.L. Ferreira1, Guilherme BauerNegrini1, Livia Silva1, Firoza Z. Lussier1, Matheus S. Rodrigues1, Markley S. Oliveira1, Andreia S.
Rocha1, Cynthia Felix1, Emma Ruppert1, Marina Scop Medeiros1, Carolina Soares Katz1, Joseph
Masdeu2, Dana L. Tudorascu1, David Soleimani-Meigooni4, Juan Fortea5, Val Lowe6, Hwamee
Oh7, Belen Pascual2, Brian A. Gordon8, Pedro Rosa-Neto9, Suzanne Baker3, Tharick A. Pascoal1
1
University of Pittsburgh, Department of Psychiatry, Pittsburgh, PA, US
Houston Methodist Research Institute, Houston, TX, US
3
Lawrence Berkeley National Laboratory, Berkeley, CA, US
4
University of California San Francisco, Memory and Aging Center, San Francisco, CA, US
5
Hospital de la Santa Creu i Sant Pau, Sant Pau Memory Unit, Department of Neurology, Barcelona, ES
6
Mayo Clinic, Department of Radiology, Rochester, MN, US
7
Brown University, Department of Psychiatry and Human Behavior, Providence, RI, US
8
Washington University in St. Louis, Department of Radiology, St. Louis, MO, US
9
Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Douglas Research
Institute, Montreal, QC, CA
2
Background: We recently showed that plasma GFAP, a marker for astrocyte reactivity, influences tau PET
pathology in cognitively unimpaired A´-positive individuals. However, the link between GFAP and tau PET in
individuals without detectable A´ pathology was underexplored. Here, we aim to investigate the association
between plasma GFAP and tau PET in cognitively unimpaired A´ PET-negative individuals.
Methods: We studied 133 cognitively unimpaired (CU) A´ PET-negative participants from the HEAD cohort with
plasma GFAP and p-tau217, as well as tau PET flortaucipir and MK6240 data. A´ positivity was determined by A´
PET visual reading or Centiloid 12. Voxel-wise linear regression models tested the association of plasma GFAP and
p-tau217 with tau PET. GFAP levels were further stratified into quartiles. SUVR in the entorhinal cortex was
compared using ANOVA across GFAP quartiles.
Results: Voxel-wise analysis showed that plasma GFAP levels (but not plasma p-tau217 levels) were associated
with tau PET in the medial temporal (e.g., amygdala, entorhinal cortex, hippocampus) and posterior cingulate
cortices, predominantly for the tracer flortaucipir (Figure 1A, B, C, D). The association between plasma p-tau217
and tau PET was weak. These results were similar when A´ positivity was defined based on Centiloid 12.
Furthermore, plasma GFAP and tau PET association in the ROI entorhinal region was significant for flortaucipir but
not for MK6240 [flortaucipir: ´=0.22966, p=0.0081; MK6240: ´=0.1296, p=0.1387; Figure 2A, B]. Flortaucipir SUVR
was slightly increased in the GFAP 4th quartile compared to the 1st quartile [flortaucipir: p=0.04; MK6240: p=0.38;
Figure 2C, D].
Conclusions: We found an association between GFAP levels and tau PET uptake in individuals not expected to
exhibit high levels of tau tangle-related tracer uptake. If these preliminary results hold, further studies could be
designed to elucidate the underpinning of this association, which could represent low levels of tau pathology,
astrogliosis, or other factors.
HAI2025 - 602
