HAI Book 2025 - Flipbook - Page 590
Silva Oliveira Junior, Markley
137
Vascular pathology influences the association of tau-PET with
neurodegeneration and cognition in Aβ-negative individuals
Markley Silva Oliveira Junior1, Bruna Bellaver1, Pamela C.L. Ferreira1, Guilherme Povala1,
Guilherme Bauer-Negrini1, Firoza Lussier1, Livia do Amaral1, Matheus Rodrigues1, Andrea da
Rocha1, Pampa Saha1, Emma Ruppert1, Carolina Soares1, Douglas Leffa1, Cynthia Felix1, Rayan
Mroue1, Dana Tudorascu1, Hussein Zalzale1, Belen Pascual2, Brian Gordon3, Val Lowe4,
Hwamee Oh5, David Soleimani-Meigooni6, Juan Fortea8, Pedro Rosa-Neto8, Suzanne Baker9,
Tharick Pascoal1
1
University of Pittsburgh, Department of Psychiatry, Pittsburgh, PA, US
Houston Methodist Research Institute, Department of Neurology, Houston, TX, US
3
Washington University in St. Louis, Department of Radiology, St. Louis, MO, US
4
Mayo Clinic, Department of Radiology, Rochester, MN, US
5
Brown University, Department of Psychiatry and Human Behavior,, Providence, RI, US
6
University of California San Francisco, Memory and Aging Center,, San Francisco, CA, US
7
Hospital de la Santa Creu i Sant Pau, Sant Pau Memory Unit, Barcelona, ES
8
Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Douglas Research
Institute,, Montreal, QC, CA
9
Lawrence Berkeley National Laboratory,, Berkeley, CA, US
2
Background: Previous studies have linked the coexistence of amyloid-´ (A´) and vascular pathology burden (VP)
with early tau PET accumulation in Alzheimer's disease (AD). However, the impact of VP on tau PET deposition and
its relationship to neurodegeneration and cognitive decline in A´-negative individuals remains unclear.
Methods: We analyzed 211 A´-PET negative participants (Centiloid < 20) from the HEAD study, including CDR-SB,
plasma NfL, ptau217, T1-based volumetrics, [18F]Flortaucipir (FTP), and [18F]MK6240 (MK). VP risk factors tested
were hypertension, diabetes, dyslipidemia, tobacco use, and white matter hyperintensity (WMH). Fazekas score 23. Participants were categorized into low/negative VP (0-1 risk factors; n = 114) and high/positive VP (2-5 risk
factors; n = 97). Group differences were analyzed using ANCOVA, and associations were assessed using linear
regressions accounting for age, sex, education, and cognitive status.
Results: A´-negative individuals with high VP showed more brain atrophy (Fig. 1A; P = 0.0160), higher plasma NfL
(Fig. 1B; P < 0.0001), and elevated ptau217 levels (Fig. 1C; P = 0.0438). A´ Centiloid levels and FTP uptake were
similar between VP groups (Fig. 1D, 1E, 1F, 1H). The high VP group showed lower MTL MK uptake (Fig. 1G; P = 0.0115).
FTP levels in the MTL and Neotemporal cortex were significantly associated with cognitive decline (Fig. 3A; ´:
0.2618, P = 0.0005) and brain atrophy (Fig. 3B; ´: -0.2444, P = 0.0037) only in the high VP group. VP did not alter the
association between MK and cognition or atrophy (Fig. 2A-D).
Discussion: VP was associated with brain atrophy, elevated plasma NfL, and ptau217 in A´-negative individuals.
VP influenced the relationship between FTP, but not MK, with cognitive impairment and brain atrophy. Future
analyses should replicate these findings and explore the underlying mechanisms of these differences.
HAI2025 - 590
