Feb 1, 2005
Nanoparticle technique detects Alzheimer's-related proteins
Researchers from Northwestern University, US, and Rush University, US, have used their nanoparticle-based bio-barcode assay to measure the concentration of amyloid-β-diffusible ligands (ADDLs) in cerebrospinal fluid (CSF). Since ADDLs are likely to be markers for Alzheimer's disease, the technique could provide a method for early and reliable diagnosis of the condition.
"We have demonstrated the first diagnostic test for the potential Alzheimer's biomarker known as an ADDL," said Chad Mirkin, director of Northwestern's Institute for Nanotechnology. "This protein is only 5 nm wide and present in cerebrospinal fluid at very low concentration, making it difficult to detect. Our bio-barcode-amplification technology, which is a million times more sensitive than any other diagnostic technology, can accurately identify ADDLs even in CSF."
The bio-barcode-amplification technique uses 30 nm-diameter gold nanoparticles and magnetic microparticles. Both types of particle are attached to an antibody for ADDLs, while the nanoparticles also link to hundreds of strands of "barcode" DNA.
Because of the antibodies, each ADDL molecule binds to a gold nanoparticle and a magnetic microparticle. Using a magnetic field enables the scientists to separate out the ADDL molecules and their attachments. Then they remove the barcode DNA from the molecules and detect it by a standard chip-based DNA detection method. Since each nanoparticle links to a large number of strands of barcode DNA, the method amplifies the signal from each ADDL molecule.
The researchers measured ADDL concentrations in the cerebrospinal fluid of 30 individual humans. Half the individuals had been diagnosed with Alzheimer's disease, while the other half were from a control group. The ADDL concentrations in the individuals with Alzheimer's were consistently higher than the levels for the control group.
Currently, diagnosing Alzheimer's disease involves examining a patient's clinical history, brain imaging to look for plaques and neuropsychological, cognitive and neurological tests. However, the results are only about 85% accurate.
"Detection of plaques in patients may be too late," said William Klein, professor of neurobiology and physiology at Northwestern. "In the last three years, there has been a big effort in Alzheimer's research to identify and detect biomarkers in cerebrospinal fluid. We think the accumulation of ADDLs is likely to be the first biomarker in Alzheimer's disease. Now this extraordinarily powerful detection technology has changed what we think might be possible."
The researchers say they would like to develop the test for blood or urine samples, which are easier to obtain than cerebrospinal fluid.
They also reckon the method could detect biomarkers for diseases such as HIV infection, various cancers and Creutzfeldt-Jakob disease. This would enable earlier diagnosis than is currently possible with conventional technology.
The researchers reported their work in the Proceedings of the National Academy of Sciences.
About the author
Liz Kalaugher is editor of nanotechweb.org.