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Interaction of the amyloid imaging tracer FDDNP with hallmark Alzheimer’s disease pathologies
Author(s) -
Thompson Paul W.,
Ye Liang,
Morgenstern Jennifer L.,
Sue Lucia,
Beach Thomas G.,
Judd Duncan J.,
Shipley Nicholas J.,
Libri Vincenzo,
Lockhart Andrew
Publication year - 2009
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/j.1471-4159.2009.05996.x
Subject(s) - senile plaques , angiopathy , chemistry , cerebral amyloid angiopathy , radioligand , pittsburgh compound b , alzheimer's disease , amyloid (mycology) , fibril , neuropathology , pathology , biochemistry , binding site , medicine , endocrinology , dementia , disease , inorganic chemistry , diabetes mellitus
The distinctive cortical uptake of the tracer 18 F‐FDDNP (2‐(1‐{6‐[(2‐fluoroethyl(methyl)amino]‐2‐naphthyl}ethylidene)malononitrile) in Alzheimer’s disease (AD) is believed to be because of its binding to both neurofibrillary tangles (NFTs) and highly fibrillar senile plaques. We therefore investigated the binding of a tracer concentration of 3 H‐FDDNP to brain sections containing AD hallmark pathologies. Semi‐adjacent sections were labelled with 3 H‐PIB (Pittsburgh compound‐B, 2‐[4′‐(methylamino)phenyl]‐6‐hydroxybenzothiazole) and 14 C‐SB13 (4‐ N ‐methylamino‐4′‐hydroxystilbene) for comparison. Neocortical sections containing widespread senile plaques and cerebrovascular amyloid angiopathy, produced a sparse and weak labelling following incubation with 3 H‐FDDNP. Furthermore, in sections containing NFTs, there was no overt labelling of the pathology by 3 H‐FDDNP. In contrast, sections labelled with 3 H‐PIB displayed extensive labelling of diffuse plaques, classical plaques, cerebrovascular amyloid angiopathy and NFTs. 14 C‐SB13 produced a broadly similar binding pattern to PIB. Radioligand binding assays employing in vitro generated amyloid‐β peptide fibrils demonstrated a ∼10‐fold reduced affinity for 3 H‐FDDNP (85.0 ± 2.0 nM) compared with 3 H‐PIB (8.5 ± 1.3 nM). These data provide an alternative mechanistic explanation for the observed low cortical uptake of 18 F‐FDDNP in AD; in that the ligand is only weakly retained by the hallmark neuropathology because of its low affinity for amyloid structures.