Ruiqing Ni1, Per-Göran Gillberg1, Nenad Bogdanovic2, Matti Viitanen3, Liisa Myllykangas4, Inger Nennesmo5, Bengt Långström6, Agneta Nordberg7. 1. Division of Translational Alzheimer Neurobiology, Department of Neurobiology Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden. 2. Division of Clinical Geriatrics, Department of Neurobiology Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, University of Oslo, Oslo, Norway. 3. Division of Clinical Geriatrics, Department of Neurobiology Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden. 4. Department of Pathology, University of Helsinki, Helsinki, Finland. 5. Division of Pathology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden. 6. Department of Chemistry, Uppsala University, Uppsala, Sweden. 7. Division of Translational Alzheimer Neurobiology, Department of Neurobiology Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden. Electronic address: Agneta.K.Nordberg@ki.se.
Abstract
INTRODUCTION: Amyloid imaging has been integrated into diagnostic criteria for Alzheimer's disease (AD). How amyloid tracers binding differ for different tracer structures and amyloid-β aggregates in autosomal dominant AD (ADAD) and sporadic AD is unclear. METHODS: Binding properties of different amyloid tracers were examined in brain homogenates from six ADAD with APPswe, PS1 M146V, and PS1 EΔ9 mutations, 13 sporadic AD, and 14 control cases. RESULTS: 3H-PIB, 3H-florbetaben, 3H-AZD2184, and BTA-1 shared a high- and a varying low-affinity binding site in the frontal cortex of sporadic AD. AZD2184 detected another binding site (affinity 33 nM) in the frontal cortex of ADAD. The 3H-AZD2184 and 3H-PIB binding were significantly higher in the striatum of ADAD compared to sporadic AD and control. Polyphenol resveratrol showed strongest inhibition on 3H-AZD84 binding followed by 3H-florbetaben and minimal on 3H-PIB. DISCUSSION: This study implies amyloid tracers of different structures detect different sites on amyloid-β fibrils or conformations.
INTRODUCTION: Amyloid imaging has been integrated into diagnostic criteria for Alzheimer's disease (AD). How amyloid tracers binding differ for different tracer structures and amyloid-β aggregates in autosomal dominant AD (ADAD) and sporadic AD is unclear. METHODS: Binding properties of different amyloid tracers were examined in brain homogenates from six ADAD with APPswe, PS1M146V, and PS1 EΔ9 mutations, 13 sporadic AD, and 14 control cases. RESULTS:3H-PIB, 3H-florbetaben, 3H-AZD2184, and BTA-1 shared a high- and a varying low-affinity binding site in the frontal cortex of sporadic AD. AZD2184 detected another binding site (affinity 33 nM) in the frontal cortex of ADAD. The 3H-AZD2184 and 3H-PIB binding were significantly higher in the striatum of ADAD compared to sporadic AD and control. Polyphenolresveratrol showed strongest inhibition on 3H-AZD84 binding followed by 3H-florbetaben and minimal on 3H-PIB. DISCUSSION: This study implies amyloid tracers of different structures detect different sites on amyloid-β fibrils or conformations.
Authors: Sylvia E Perez; Jennifer C Miguel; Bin He; Michael Malek-Ahmadi; Eric E Abrahamson; Milos D Ikonomovic; Ira Lott; Eric Doran; Melissa J Alldred; Stephen D Ginsberg; Elliott J Mufson Journal: Acta Neuropathol Date: 2019-02-07 Impact factor: 17.088
Authors: Ruiqing Ni; Zhenyue Chen; Xosé Luís Deán-Ben; Fabian F Voigt; Daniel Kirschenbaum; Gloria Shi; Alessia Villois; Quanyu Zhou; Alessandro Crimi; Paolo Arosio; Roger M Nitsch; K Peter R Nilsson; Adriano Aguzzi; Fritjof Helmchen; Jan Klohs; Daniel Razansky Journal: Nat Biomed Eng Date: 2022-07-14 Impact factor: 29.234