Journal Article

DZNE-2026-00783

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Associations of [18F]PI-2620 Binding with Memory and Phosphorylated Tau 217 in Cognitively Unimpaired Older Adults.

Maass, A.DZNE* ; Garcia-Garcia, B.DZNE* ; Behrenbruch, N.DZNE* ; Schumann-Werner, B.DZNE* ; Molloy, E. N.DZNE* ; Schwarck, S.DZNE* ; Rullmann, M. ; Hochkeppler, A.DZNE* ; Fischer, L.DZNE* ; Büchel, A.-T.DZNE* ; Bernal, J.DZNE* ; Vockert, N.DZNE* ; Incesoy, E. I.DZNE* ; Glanz, W.DZNE* ; Butryn, M.DZNE* ; Schulze, P.DZNE* ; Baldauf, K.DZNE* ; Stephens, A. W. ; Schildan, A. ; Patt, M. ; Behnisch, G. ; Morgado, B.DZNE* ; Esselmann, H. ; Seidenbecher, C. I. ; Schott, B. H.DZNE* ; Wiltfang, J.DZNE* ; Barthel, H. ; Sabri, O.Extern* ; Kreissl, M. C.DZNE* ; Düzel, E. (Last author)DZNE*

2026
Soc. New York, NY

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Please use a persistent id in citations: 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], Aβ1-42/Aβ1-40), 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 ± 7 y; females, 46%; apolipoprotein ϵ4 [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 (β = 0.543, P < 0.001) and APOE4 carriers (β = 0.395, P = 0.030) and was positively associated with plasma p-tau217 (β = 0.22, P = 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 (β = -0.36, P = 0.003) and lower hippocampal volume (β = 0.22, P = 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.

Keyword(s): Alzheimer disease ; PI-2620 ; episodic memory ; phospho-tau 217 ; tau PET

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Contributing Institute(s):

1. Clinical Neurophysiology and Memory (AG Düzel)
2. Multimodal Neuroimaging (AG Maaß)
3. Molecular biomarkers for predictive diagnostics of neurodegenerative diseases (AG Wiltfang)
4. Epigenetics and Systems Medicine in Neurodegenerative Diseases (AG Fischer)
5. Core MR PET (Core MR PET)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)
3. 899 - ohne Topic (POF4-899) (POF4-899)

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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