Angewandte Chemie International Edition
© WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2005, 44, 5452–5456
Early Detection of Alzheimer’s Coming Soon?
Progress on contrast agents that make amyloid deposits in the brain visible
Alzheimer’s disease is the most common form of old-age dementia and has become the fourth most common cause of death in the USA. The cause of the disease is protein deposits, called amyloid plaques, in the brain. Until now, it has only been possible to identify these plaques by autopsy, which means that unambiguous diagnosis comes only after the death of the patient. However, early detection is important for gaining a better understanding of the disease and for the development of treatments to stop its progress. Researchers are thus working on noninvasive imaging techniques for detection of the plaques. American scientists have now laid the foundation for a contrast agent that could mark the amyloid deposits.
The first noninvasive methods for the detection of plaques in the brain, which work with radioactive contrast agents, are under development. Now an interesting alternative is emerging: Optical imaging techniques with specific contrast agents that fluoresce when exposed to radiation in the near-infrared region of the spectrum. This light, with its relatively long wavelength, is able to penetrate living tissue well enough to make brain structures visible. “What we need,” says Timothy M. Swager, “ is a suitable contrast agent.” Working with a team of scientists at MIT, Massachusetts General Hospital, and the University of Pittsburgh, he has considered the requirements that such a contrast agent must fulfill: 1) It must accumulate specifically in amyloid plaques. Certain molecules with a framework of flat aromatic rings do this, such as Congo Red, which is used to stain the plaques in histological sections. 2) The substance must quickly pass the blood–brain barrier after injection in order to move from the blood to the brain. It must therefore be a small, uncharged, and slightly lipophilic (fat-friendly) molecule. 3) Its absorption and fluorescence spectra must lie in a suitable spectral range — a question of electronic structure. 4) For a particularly sharp contrast, the bound molecules should fluoresce more strongly than the unbound ones. This happens when the molecule bound to the plaques is less able to move than the free molecule. 5) It must be nontoxic.
Indeed, the researchers were able to design a molecule that fills these requirements. “In order for this first conceptual molecule to become a viable contrast agent that can make amyloid plaques visible through the skull,” says Swager, “we still have to tweak its optical properties; the fluorescence must be stronger and shifted to longer wavelengths.”