Diagnosing Alzheimer's—Before Autopsy

To treat a disease you first have to diagnose it. Although the proclivity toward developing Alzheimer's disease has been determined to be genetic, diagnosing it has so far been possible only by autopsy. This is the primary reason that no cure has been demonstrated effective. Furthermore, a diagnostic tool would help rule out the potentially life-threatening minor strokes that can bring about personality changes which mimic the onset of Alzheimer's.

Stephanie vL Henkel
Stephanie vL Henkel
 

At Northwestern University, researchers in the Departments of Chemistry and Neurobiology & Physiology have used a nanosensor to examine the behavior of molecules that may be involved with Alzheimer's. This nanosensor, which incorporates a UV/VIS spectrometer, has provided new information relevant to the understanding and possible diagnosis.

It turns out that amyloid-derived diffusible ligands (ADDLs), a minuscule toxic protein suspected of triggering the disease, is present at levels up to 70 X greater in autopsied brain samples from humans with Alzheimer's than it is in samples without the disease. A sensitive method of detecting ADDLs in body fluid could, therefore, provide a basis for the laboratory diagnosis of the disease.

The nanosensor developed for ADDLs is based on triangular silver nanoparticles that absorb and scatter light. The extinction spectrum (sum of adsorbed and scattered light) of the particles varies as their environment changes. To control this change, the nanoparticles' surfaces are modified with a layer of ADDL-specific antibodies that bind specifically to any ADDL molecules in the samples studied. When this happens, the spectral properties of the silver nanoparticles shift slightly.

Detecting toxic proteins could advance the diagnosis of Alzheimer's disease
Detecting toxic proteins could advance the diagnosis of Alzheimer's disease
 

Using this technique, the researchers were able to detect ADDL levels that were elevated in diseased patient samples in comparison to control patient samples. The researchers detected these color shifts using a fiber optically coupled spectrometer. The research has indicated the potential of nanoscale optical biosensors for the development of other successful nanotechnology-based devices.

Contact Rob Morris, Ocean Optics Inc., Dunedin, FL; 727-733-2447, [email protected], www.oceanoptics.com.