HAI Book 2025 - Flipbook - Page 456
Betthauser, Tobey
Comparison of [3H]MK-6240 and [3H]AV-1451 binding in relation to brain
concentrations of p-tau: A postmortem biochemistry study
Tobey Betthauser1, Eric Abrahamson2, Manik Debnath3, William Paljug3, Shahriar Salamat4,
Thomas Karikari3, Victor Villemagne3, Milos Ikonomovic2,3
1
University of Wisconsin-Madison, School of Medicine and Public Health, Department of Medicine, Madison, WI, US
University of Pittsburgh, Department of Neurology, Pittsburgh, PA, US
3
University of Pittsburgh, Department of Psychiatry, Pittsburgh, PA, US
4
University of Wisconsin-Madison, School of Medicine and Public Health, Department of Pathology, Madison, WI, US
2
Background: Validation studies of tau PET radioligands require assessment of tracer9s binding in relation to
regional neuropathology. Additionally, quantitative biochemical assays of regional p-tau concentrations can
facilitate interplay between imaging and plasma biomarker studies. We performed parallel analyses of [3H]MK6240 and [3H]AV-1451 in-vitro binding for comparison with p-tau concentrations in same postmortem brain tissue
extracts from autopsy cases with a range of Alzheimer9s disease (AD) neuropathologic change severity.
Methods: Study cohort consisted of 8 autopsy cases from the University of Wisconsin and University of
Pittsburgh ADRC brain banks, including cognitively unimpaired controls and AD cases with intermediate and high
AD neuropathologic changes. In all cases, frozen tissues from eleven brain regions were processed to quantify
[3H]MK-6240 and [3H]AV-1451 in-vitro binding as well as concentrations of tau pThr181, pThr231, pSer199, and
pSer396 determined by tau phospho-epitope specific ELISA.
Results: Correlations between higher [3H]MK-6240 binding and higher p-tau concentrations were strongest for
pSer396 (R=0.62, p
