Premium
Distinct binding of amyloid imaging ligands to unique amyloid‐β deposited in the presubiculum of Alzheimer's disease
Author(s) -
Ji Bin,
Chen ChunJen,
Bando Kazunori,
Ashino Hiroki,
Shiraishi Hideaki,
Sano Hiroaki,
Kasahara Hiroyuki,
Minamizawa Takao,
Yamada Kazutaka,
Ono Maiko,
Zhang MingRong,
Seki Chie,
Farde Lars,
Suhara Tetsuya,
Higuchi Makoto
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13293
Subject(s) - senile plaques , translocator protein , chemistry , amyloid (mycology) , radioligand , neurodegeneration , neurotoxicity , hippocampal formation , alzheimer's disease , neuroinflammation , neuroscience , binding site , biophysics , biochemistry , pathology , biology , medicine , disease , toxicity , inorganic chemistry , organic chemistry
Abstract Non‐invasive determination of amyloid‐β peptide (Aβ) deposition with radioligands serves for the early diagnosis and clarification of pathogenetic mechanisms of Alzheimer's disease (AD). The polymorphic binding site on multimeric Aβ for current radioligands, however, is little understood. In this study, we investigated the binding of several radioligands including 11 C‐Pittsburgh Compound B ( 11 C‐PiB), 3 H‐AZD2184, and two recently developed compounds, 125 I‐DRM106 and 125 I‐DRK092, with unique presubicular Aβ deposits lacking interaction with the commonly used amyloid dyes FSB. 11 C‐PiB, 3 H‐AZD2184, and 125 I‐DRK092 showed overt binding to presubicular Aβ deposits, while 125 I‐DRM106 barely bound to these aggregates despite its strong binding in the hippocampal CA1 sector. Unlike neuritic plaques in the CA1, Aβ lesions in the presubiculum were not accompanied by inflammatory gliosis enriched with 18‐kDa translocator protein (TSPO). Thus, there are at least two different components in Aβ aggregates providing distinct binding sites for the current amyloid radioligands, and one of these binding components is distinctly present in the presubicular Aβ deposits. Amyloid radioligands lacking affinity for this component, such as 125 I‐DRM106, may selectively capture Aβ deposits tightly associated with TSPO neuroinflammation and neurodegeneration as exemplified by CA1 neuritic plaques. Hence, comparative autoradiographic assessments of radioligand binding in CA1 and presubiculum could serve for the development of an amyloid PET imaging agent visualizing neurotoxicity‐related Aβ pathologies.Non‐invasive determination of amyloid‐β peptide (Aβ) serves for the early diagnosis and clarification of pathogenetic mechanisms of Alzheimer's disease (AD). We found that there are at least two different amyloid components in hippocampal CA1 and presubiculum providing distinct binding sites for the current amyloid radioligands. Comparative analysis for radioligand binding in these two regions could serve for developing novel imaging agents selectively visualizing neurotoxicity‐related Aβ pathologies.