HAI Book 2025 - Flipbook - Page 637
Villemagne, Victor
153
Astrogliosis in the early-stages of Alzheimer's disease
Vincent Dore1,2, Pierrick Bourgeat1, Ryuichi Harada3,4, Shozo Furumoto5, Rachel Mulligan2,
Ying Xia1, Ishara Paranawithana1,2, Simon Laws6, Azadeh Feizpour2,7, Svetlana Bozinovski2,
Kun Huang2, Brian J. Lopresti8, Milos D. Ikonomovic8,9,10, Jurgen Fripp1, Nobuyuki Okamura11,
Christopher C. Rowe2,7, Victor L. Villemagne2,8
1
The Australian e-Health Research Centre, The Commonwealth Scientific and Industrial Research Organisation
(CSIRO), Melbourne, AU
2
Department of Molecular Imaging and Therapy, Austin Health, Melbourne, AU
3
Department of Pharmacology, School of Medicine, Tohoku University, Sendai, JP
4
Institute of Development of Aging and Cancer, Tohoku University,, Sendai, JP
5
Cyclotron and Radioisotope Center, Tohoku University, Sendai, JP
6
School of Medical and Health Sciences, Edith Cowan University, Perth, AU
7
Florey Institute of Neurosciences and Mental Health, University of Melbourne, Melbourne, AU
8
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, US
9
Department of Neurology, University of Pittsburgh, Pittsburgh, PA, US
10
Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA, US
11
Division of Pharmacology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, JP
Background: Monoamine Oxidase-B (MAO-B) is overexpressed in reactive astrocytes, playing a crucial role in
neurodegeneration. Recently, increased binding of the PET MAO-B tracer 18F-SMBT-1 has been shown in
preclinical Alzheimer9s disease (AD) stages. However, the regional distribution and effect on A´ of abnormal 18FSMBT-1 binding along the AD continuum remains unclear.
Method: 133 Cognitively Unimpaired (CU), 24 A+ Mild Cognitive Impairment (MCI), and 20 A+ AD subjects underwent
PET imaging with 18F-NAV4694, 18F-MK6240, and 18F-SMBT-1. A´ and tau PET SUVR were transformed into
Centiloid (CL) and CenTauR (CTR) using CapAIBL. A+ was defined as >25CL and T+ >14CTR in the Meta-Temporal.
18
F-SMBT-1 scans were spatially normalised using MR-based CapAIBL, scaled to the cerebellar cortex and several
cortical regions sampled. The relationship between 18F-SMBT-1 binding and A´ accumulation was assessed in a
subset of 74 CU A-.
Results: Distinct regional 18F-SMBT-1 binding was observed across brain regions (Figure 1). 18F-SMBT-1 binding was
higher in CU A+ compared to the CU A- in most regions, while binding in A+ MCI/AD either remained higher (in
parietal/cingulate/occipital) or decreased (in frontal/caudate/putamen). Higher 18F-SMBT-1 binding was also
significant in CU A+ T- (n=32). In CU A- participants with high 18F-SMBT-1 retention, significantly higher A´
accumulation rates were observed compared to low 18F-SMBT-1 (1.04CL/yr vs 0.34CL/yr, respectively, p=0.01)
(Figure 2). Furthermore, 88% of CU A- individuals with high 18F-SMBT-1 were classified as A´ accumulators.
Conclusion: 18F-SMBT-1 facilitates quantitative assessment of regional differences in reactive astrogliosis across
the AD continuum, as well as longitudinal change. Elevated 18F-SMBT-1 in CU A- predicted A´ accumulation,
highlighting the potential of 18F-SMBT-1 as a prognostic marker in early-stage AD while suggesting modulation of
astrocytic function may be a target for AD prevention and treatment.
HAI2025 - 637
