GOLD nanoparticles and mini-magnets may hold the key to early detection of Alzheimer鈥檚 disease.
While brain imaging and psychological tests can help doctors diagnose suspected Alzheimer鈥檚 disease and monitor its progress, they can only be sure after autopsy.
Recent studies, however, have revealed a wealth of molecules, including proteins called amyloid-beta-diffusable-ligands (ADDLs), which are abnormally abundant in the brains of Alzheimer鈥檚 patients. These molecules could form the basis of definitive tests for the disease in living patients.
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Dimitra Georganopoulou and her colleagues at Northwestern University in Chicago thought that they might also find ADDLs in the cerebrospinal fluid, which can be collected by a spinal tap. But their concentrations would be so low that they would not be detectable by conventional methods.
So the team turned to a new technique called bio-barcoding, which is thousands of times more sensitive for protein detection. 鈥淚t鈥檚 the only tool in town that provides the necessary sensitivity,鈥� says team member Chad Mirkin.
Each ADDL molecule gets trapped by a pair of different antibodies. One antibody is attached to a large magnetised particle. The other is attached to a gold nanoparticle coated with thousands of DNA strands.
Once trapped by this pincer movement, which makes it magnetic, each ADDL can be drawn to one side of a test tube by a magnetic field. The DNA strands are then chemically released from the gold and counted to give an ADDL concentration.
鈥淏io-barcoding is the only tool in town that provides the sensitivity necessary for detecting suspect proteins鈥�
The team used the technique to screen for ADDLs in cerebrospinal fluid from 15 patients who had died of Alzheimer鈥檚 (which was confirmed at post-mortem) and did the same at autopsy for a similarly aged group who had not died of the condition. Sure enough, cerebrospinal fluid from the patients with Alzheimer鈥檚 contained much more ADDL than that from unaffected people. (Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0409336102).
Georganopoulou hopes eventually to use the test on blood samples, which are much easier to collect.
