February 17, 2005

New test is first step in early detection of Alzheimer’s

By Megan Fellman

A new use of an ultra-sensitive method that employs bionanotechnology might lead to a clinical test capable of diagnosing Alzheimer’s disease in its earliest stages — instead of during an autopsy.

Scientists at Northwestern have become the first to detect in living humans a biomarker associated with Alzheimer’s disease, a development that promises early intervention when therapeutics may be most effective — long before plaques and tangles develop in the brain and dementia sets in.

A study by the Northwestern team shows that bio-bar-code amplification (BCA) technology, which was developed at the University, can detect in human cerebrospinal fluid (CSF) miniscule amounts of a toxic protein that may be responsible for the early neurological deterioration in Alzheimer’s disease. The findings are published online by the Proceedings of the National Academy of Sciences (PNAS).

“We have demonstrated the first diagnostic test for the potential Alzheimer’s biomarker known as an ADDL,” said Chad A. Mirkin, director of the Institute for Nanotechnology at Northwestern and an author on the PNAS paper. “This protein is only five nanometers wide and present in cerebrospinal fluid at very low concentration, making it very difficult to detect. Our BCA technology, which is a million times more sensitive than any other diagnostic technology, can accurately identify ADDLs, even in CSF.”

Amyloid ß-derived diffusible ligands or ADDLs (pronounced “addles”) are small, soluble aggregated proteins. The clinical data strongly support a recent theory in which ADDLs accumulate at the beginning of Alzheimer’s disease and block memory function by a process predicted to be reversible. William L. Klein, professor of neurobiology and physiology in Northwestern’s Weinberg College of Arts and Sciences, and two colleagues reported the discovery of ADDLs in 1998.

“Detection of plaques in patients may be too late,” said Klein, an author on the PNAS paper who last year demonstrated that ADDLs specifically attack and disrupt synapses, the nerve cell sites responsible for information processing and memory formation. “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, and now this extraordinarily powerful detection technology has changed what we think might be possible.”