NDLI: Detection of amyloid plaques by radioligands for Aβ40 and Aβ42 : Potential imaging agents in alzheimer’s patients

Content Provider	Springer Nature Link
Author	Kung, Mei Ping Skovronsky, Daniel M. Hou, Catherine Zhuang, Zhi Ping Gur, Tamar L. Zhang, Bin Trojawski, John Q. Lee, Virginia M. Y. Kung, Hank F.
Copyright Year	2003
Abstract	Alzheimer’s disease (AD) is linked to increased brain deposition of amyloid-β (Aβ) peptides in senile plaques (SPs), and recent therapeutic efforts have focused on inhibiting the production or enhancing the clearance of Aβ in brain. However, it has not been possible to measure the burden of SPs or assess the effect of potential therapies on brain Aβ levels in patients. Toward that end, we have developed a novel radioligand, [$^{125}$I]TZDM, which binds Aβ fibrils with high affinity, crosses the blood-brain barrier (BBB), and labels amyloid plaques in vivo. Compared to a styrylbenzene probe, [$^{125}$I]IMSB, [$^{125}$I]TZDM showed a 10-fold greater brain penetration and labeled plaques with higher sensitivity for in vivo imaging. However, this ligand also labels white matter, which contributes to undesirable high background regions of the brain. Interestingly, parallel to their differential binding characteristics onto fibrils composed of 40 (Aβ40)- or 42 (Aβ42)-amino-acid-long forms of Aβ peptides, these radioligands displayed differential labeling of SPs in AD brain sections under our experimental conditions. It was observed that [$^{125}$I]IMSB labeled SPs containing Aβ40, amyloid angiopathy (AA), and neurofibrillary tangles, whereas [$^{125}$I]TZDM detected only SPs and Aβ42-positive AA. Since increased production and deposition of Aβ42 relative to Aβ40 may be crucial for the generation of SPs, [$^{125}$I]TZDM and related derivatives may be more attractive probes for in vivo plaque labeling. Further structural modifications of TZDM to lower the background labeling will be needed to optimize the plaque-labeling property.
Starting Page	15
Ending Page	23
Page Count	9
File Format	PDF
ISSN	08958696
Journal	Journal of Molecular Neuroscience
Volume Number	20
Issue Number	1
e-ISSN	15591166
Language	English
Publisher	Humana Press
Publisher Date	2003-01-01
Publisher Place	Totowa
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Neurosciences Neurology
Content Type	Text
Resource Type	Article
Subject	Medicine Cellular and Molecular Neuroscience

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