Associations of [18F]PI-2620 Binding with Memory and Phosphorylated Tau 217 in Cognitively Unimpaired Older Adults

Maass A, Garcia-Garcia B, Behrenbruch N, Schumann-Werner B, Molloy EN, Schwarck S, Rullmann M, Hochkeppler A, Fischer L, Buchel AT, Bernal JB, Vockert N, Incesoy EI, Glanz W, Butryn M, Schulze P, Baldauf K, Stephens AW, Schildan A, Patt M, Behnisch G, Morgado B, Esselmann H, Seidenbecher CI, Schott BH, Wiltfang J, Barthel H, Sabri O, Kreissl MC, Déuzel E (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Journal of Nuclear Medicine Society of Nuclear Medicine

Pages Range: 1-9

DOI: 10.2967/jnumed.125.271927

Abstract

[¹⁸F]PI-2620 is a second-generation tau PET tracer that may detect early tau accumulation in aging. We investigated whether temporal lobe [¹⁸F]PI-2620 binding is associated with age, sex, genetic Alzheimer disease (AD) risk, plasma biomarkers of AD (plasma phosphorylated tau 217 [p-tau217], Ab1–42/Ab1–40), astrogliosis (glial fibrillary acidic protein), and domain-specific cognition in cognitively unimpaired (CU) older adults. Methods: In this study, 166 CU older adults (mean age, 72 6 7 y; females, 46%; apolipoprotein e4 [APOE4] carriers, 23%) and 13 young adults underwent extensive cognitive testing, blood sampling, MRI, and dynamic [¹⁸F]PI-2620 PET (0–60 min postinjection). Associations of regional [¹⁸F]PI-2620 distribution volume ratio (DVR) with age, sex, APOE4 genotype, and plasma biomarkers were examined using region-of-interest and voxelwise analyses. Additional imaging markers of age-related pathology included hippocampal volume, medial temporal lobe thickness, white matter (WM) hyperintensities, perivascular spaces, and hippocampal perfusion (R1-derived maps). Associations among temporal lobe DVR, other imaging markers, and domain-specific cognitive performance (from factor analysis) were tested. Results: In older adults, temporal [¹⁸F]PI-2620 binding was higher in women (b 5 0.543, P, 0.001) and APOE4 carriers (b 5 0.395, P 5 0.030) and was positively associated with plasma p-tau217 (b 5 0.22, P 5 0.008). Voxelwise analyses showed age-related increases in basal ganglia signal, whereas WM signal was higher in younger adults. In a multiple regression model, higher temporal DVR (b 5 20.36, P 5 0.003) and lower hippocampal volume (b 5 0.22, P 5 0.007) predicted worse episodic memory and, together with demographic factors, explained approximately 30% of the variance. Conclusion: Temporal [¹⁸F]PI-2620 binding is associated with genetic AD risk, plasma p-tau217, female sex, and episodic memory deficits in CU older adults, supporting its sensitivity to early tau pathology, while highlighting the need to consider potential WM binding.

Authors with CRIS profile

Jose Bernal Moyano

Involved external institutions

Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)

Germany (DE) Universitätsklinikum Leipzig

Germany (DE) Piramal Enterprises limited

India (IN) Universitätsklinikum Augsburg

Germany (DE) Leibniz-Institut für Neurobiologie (LIN)

Germany (DE) Universitätsklinikum Göttingen

Germany (DE) Zentrum für neurowissenschaftliche Forschung / Center for Behavioral Brain Sciences (CBBS)

Germany (DE) Städtisches Klinikum Dessau

Germany (DE) University of Aveiro / Universidade de Aveiro

Portugal (PT)

How to cite

APA:

Maass, A., Garcia-Garcia, B., Behrenbruch, N., Schumann-Werner, B., Molloy, E.N., Schwarck, S.,... Déuzel, E. (2026). Associations of [18F]PI-2620 Binding with Memory and Phosphorylated Tau 217 in Cognitively Unimpaired Older Adults. Journal of Nuclear Medicine, 1-9. https://doi.org/10.2967/jnumed.125.271927

MLA:

Maass, Anne, et al. "Associations of [18F]PI-2620 Binding with Memory and Phosphorylated Tau 217 in Cognitively Unimpaired Older Adults." Journal of Nuclear Medicine (2026): 1-9.

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