New Non-Invasive Method Can Detect Alzheimer's Disease Early


New Non-Invasive Method Can Detect Alzheimer's Disease Early
Brain sections from an aged Alzheimer’s mouse model were
 probed with antibodies against Abeta oligomers (568-NU4)
and amyloid plaques (ThioS). Images demonstrate that Abeta
oligomers (568-NU4) are often associated with, yet distinct
from, amyloid plaques (ThioS). NU4 labelling is more abundant
than the ThioS staining. Data supports the notion that NU4
thus affords an excellent targeting antibody for the development
of an AβO-specific MRI probe that is distinct from currently
available plaque probes. (Adapted from Viola et al., Nature
Nanotechnology, 2014.)
No methods currently exist for the early detection of Alzheimer's disease, which affects one out of nine people over the age of 65. Now, scientists have developed a noninvasive MRI approach that can detect the disease in a living animal. And it can do so at the earliest stages of the disease, well before typical Alzheimer's symptoms appear. Details of the new Alzheimer's disease diagnostic are published in the journal Nature Nanotechnology
 
The research team developed an MRI (magnetic resonance imaging) probe that pairs a magnetic nanostructure (MNS) with an antibody that seeks out the amyloid beta brain toxins responsible for onset of the disease. The accumulated toxins, because of the associated magnetic nanostructures, show up as dark areas in MRI scans of the brain.
 
This ability to detect the molecular toxins may one day enable scientists to both spot trouble early and better design drugs or therapies to combat and monitor the disease. And, while not the focus of the study, early evidence suggests the MRI probe improves memory, too, by binding to the toxins to render them "handcuffed" to do further damage.
 
The emotional and economic impacts of Alzheimer's disease are devastating. This year, the direct cost of the disease in the United States is more than $200 billion, according to the Alzheimer's Association's "2014 Alzheimer's Disease Facts and Figures." By the year 2050, that cost is expected to be $1.1 trillion as baby boomers age. And these figures do not account for the lost time of caregivers.
 
This new MRI probe technology is detecting something different from conventional technology: toxic amyloid beta oligomers instead of plaques, which occur at a stage of Alzheimer's when therapeutic intervention would be very late. Amyloid beta oligomers now are widely believed to be the culprit in the onset of Alzheimer's disease and subsequent memory loss.
 
In a diseased brain, the mobile amyloid beta oligomers attack the synapses of neurons, destroying memory and ultimately resulting in neuron death. As time progresses, the amyloid beta builds up and starts to stick together, forming the amyloid plaques that current probes target. Oligomers may appear more than a decade before plaques are detected.
 
The nontoxic MRI probe was delivered intranasally to mouse models with Alzheimer's disease and control animals without the disease. In animals with Alzheimer's, the toxins' presence can be seen clearly in the hippocampus in MRI scans of the brain. No dark areas, however, were seen in the hippocampus of the control group.
 
The ability to detect amyloid beta oligomers, is important for two reasons: amyloid beta oligomers are the toxins that damage neurons, and the oligomers are the first sign of trouble in the disease process, appearing before any other pathology. The researchers also observed that the behavior of animals with Alzheimer's improved even after receiving a single dose of the MRI probe.
 
Along with the studies in live animals, the research team also studied human brain tissue from Northwestern's Cognitive Neurology and Alzheimer's Disease Center. The samples were from individuals who died from Alzheimer's and those who did not have the disease. After introducing the MRI probe, the researchers saw large dark areas in the Alzheimer brains, indicating the presence of amyloid beta oligomers.
 
The researchers expect to use this tool to detect Alzheimer's early and to help identify drugs that can effectively eliminate the toxin and improve health.