HAI Book 2025 - Flipbook - Page 143
Abu Raya, Maison
18
Characterizing amyloid-positive with low Tau (A+T-) profiles and their
association with cognitive trajectories in the Longitudinal Early-Onset
Alzheimer9s Disease Study (LEADS): A multi-method approach
Maison Abu Raya1,2, David Soleimani-Meigooni1, Daniel R. Schonhaut1, Ganna Blazhenets1,
Konstantinos Chiotis1, Julien Lagarde8, Agathe Vrillon1,2, Piyush Maiti1, Charles Windon1,2,
Ehud Zeltzer1, Jiaxiuxiu Zhang1, Claire Yballa1, Ranjani Shankar1, Alinda Amuiri1, Salma Rocha1,
Dustin B. Hammers6, Ani Eloyan4, Maria C. Carrillo3, Robert Koeppe5, Bradford C. Dickerson7,
Liana G. Apostolova6, Gil D. Rabinovici1, Renaud La Joie1,2
1
Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San
Francisco, San Francisco, San Francisco, CA, US
2
Global Brain Health Institute- University of California San Francisco, San Francisco, CA, US
3
Medical & Scientific Relations Division, Alzheimer’s Association, Chicago, IL, US
4
Department of Biostatistics, Brown University School of Public Health, Providence, RI, US
5
Department of Radiology, University of Michigan, Ann Arbor, MI, US
6
Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, US
7
Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, US
8
Hôpital Ste Anne – GHU Paris Psychiatrie & Neurosciences – Paris, Paris, FR
Introduction: The interpretation of an A+T- PET profile in clinically impaired individuals can make it difficult to
identify underlying etiology and predict future outcomes. We aimed to assess the frequency of A+T- profiles
within a cohort of patients diagnosed with early-onset Alzheimer9s Disease (EOAD) and describe their clinical and
imaging characteristics.
Methods: We analyzed 582 LEADS participants with baseline [18F]florbetaben and [18F]flortaucipir PET: 490
cognitively impaired (CI, i.e., clinical diagnosis of MCI or dementia) and 92 cognitively unimpaired (CU)
participants. Amyloid positivity (A+) was defined using a 25-CL threshold. Tau-PET status was based on visual
read following FDA-approved guidelines or SUVR extractions from various ROIs (in native space using Freesurfer
or in template space with CenTauR procedures). Regional flortaucipir-SUVR thresholds were calculated using
various statistical methods (Table 1).
Results: Among 372 A+ CI participants, rates of T- were minimal (4%-7%), regardless of the tau-PET approach
(Table1). Subsequent analyses focused on comparing A+T+ and A+T- groups, defined using the two methods that
provided the most divergent T- rates, which were visual reads (4%) or global cortical SUVR thresholds calculated
using a Gaussian Mixture Model-based approach (7%). Regardless of the tau status definitions, the A+T- group
exhibited milder clinical impairment than the A+T+ group despite being older and having a higher frequency of
APOE-e4, hypercholesterolemia, and smoking (Table 2). The A+T- group had lower amyloid burden and larger
hippocampal volumes than A+T+ patients but similar white matter hypointensity burden. Regardless of Tau status,
all groups ( A+TVisual Read/Global+/-) showed an increase in CDR-SB over time, but clinical progression was more rapid in
the A+T+ groups (Figure 1).
Conclusion: In amyloid-positive patients with EOAD, tau-PET results were predominantly positive regardless of
tau-status definitions (93-96%). Some of the rare A+T- individuals may be in early disease stages, with tau
pathology below PET detection levels.
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