Amyloid tracers binding sites in autosomal dominant and sporadic Alzheimer's disease.
BACKGROUND
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. The3H-AZD2184 and3H-PIB binding were significantly higher in the striatum of ADAD compared to sporadic AD and control. Polyphenol resveratrol showed strongest inhibition on3H-AZD84 binding followed by3H-florbetaben and minimal on3H-PIB.


CONCLUSIONS
This study implies amyloid tracers of different structures detect different sites on amyloid-β fibrils or conformations.
Division of Translational Alzheimer Neurobiology, Department of Neurobiology Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.
Ruiqing
R
Ni
Division of Translational Alzheimer Neurobiology, Department of Neurobiology Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.
Per-Göran
PG
Gillberg
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.
Nenad
N
Bogdanovic
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.
Matti
M
Viitanen
Department of Pathology, University of Helsinki, Helsinki, Finland.
Liisa
L
Myllykangas
Division of Pathology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Inger
I
Nennesmo
Department of Chemistry, Uppsala University, Uppsala, Sweden.
Bengt
B
Långström
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.
Agneta
A
Nordberg
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001667:Binding, Competitive; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D002491:Central Nervous System Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics*
D016229:Amyloid beta-Peptides; D002491:Central Nervous System Agents; D019275:Radiopharmaceuticals
AZD2184; Alzheimer's disease; Amyloid-β; Autosomal dominant Alzheimer's disease; Florbetaben; Pittsburgh compound B; Positron emission tomography; Resveratrol