Alzheimer's Disease Research
Hyperspectral imaging for early detection of Alzheimer’s disease
Amyloidopathic disorders such as Alzheimer’s disease present symptomology years following the entrenchment of amyloidogenic imbalance. Symptomology often presents only after significant neurodegeneration. There exists thus a warrant for early detection of amyloidopathy in Alzheimer’s disease. Non-existent modalities for direct identification and quantitation of soluble amyloid aggregates or (proto)fibrils forced us to undertake the development of a spectrophotometric technique to support ongoing drug design. Key requirements were independence from the need for extraneous staining, unambiguous amyloid aggregate detection and minimal influence of interpretative errors.
A Cytoviva® instrument pivotal to this study captures scattering of light of the visible–near infrared (VNIR, 400–1000 nm) wavelengths within each pixel of the microscopic view field. Assembled thusly was a scatterance intensity pattern database that lent “signatures” of amyloid aggregates.
Comparison of unknown samples against this database enabled direct detection of amyloid aggregates. The technique was found useful for monitoring retinal and brain amyloidopathy in an ongoing preclinical anti-AD study, attesting to the technique’s sensitivity and specificity. Interestingly, the technique was found applicable not just to excised brain tissue, but also to isolated mouse retina. With the retina being heralded widely as a (diagnostic) extension of the CNS and retinal amyloidopathy occurring well before that in the brain, this development raises a possibility for the first direct retinal imaging diagnosis of early, asymptomatic Alzheimer’s disease.
Food flavorants increase amyloid aggregation in brain
A new study raises concern about chronic exposure of workers in industry to a food flavoring ingredient used to produce the distinctive buttery flavor and aroma of microwave popcorn, margarines, snack foods, candy, baked goods, pet foods and other products. It found evidence that the ingredient, diacetyl (DA), intensifies the damaging effects of an abnormal brain protein linked to Alzheimer’s disease. The study appears in ACS’ journal Chemical Research in Toxicology.
Robert Vince and colleagues Swati More and Ashish Vartak explain that DA has been the focus of much research recently because it is linked to respiratory and other problems in workers at microwave popcorn and food-flavoring factories. DA gives microwave popcorn its distinctive buttery taste and aroma. DA also forms naturally in fermented beverages such as beer, and gives some chardonnay wines a buttery taste. Vince’s team realized that DA has an architecture similar to a substance that makes beta-amyloid proteins clump together in the brain — clumping being a hallmark of Alzheimer’s disease. So they tested whether DA also could clump those proteins.
DA did increase the level of beta-amyloid clumping. At real-world occupational exposure levels, DA also enhanced beta-amyloid’s toxic effects on nerve cells growing in the laboratory. Other lab experiments showed that DA easily penetrated the so-called “blood-brain barrier,” which keeps many harmful substances from entering the brain. DA also stopped a protective protein called glyoxalase I from safeguarding nerve cells. “In light of the chronic exposure of industry workers to DA, this study raises the troubling possibility of long-term neurological toxicity mediated by DA,” say the researchers.
Implications of chronic exposure to Diacetyl on human health
Diacetyl (DA), an ubiquitous butter-flavoring agent, was found to influence several aspects of amyloid-β (Aβ) aggregation—one of the two primary pathologies associated with Alzheimer's disease. Additionally, DA was found not only to be resistant to but also inhibitory toward glyoxalase I, the primary initiator of detoxification of amyloid-promoting reactive dicarbonyl species that are generated naturally in large amounts by neuronal tissue.
Other effects of DA
DA increases the level of beta-amyloid clumping at real-world occupational exposure levels. At such exposure levels, DA also enhanced beta-amyloid’s toxic effects on nerve cells growing in the laboratory. Other lab experiments showed that DA easily penetrated the so-called “blood-brain barrier,” which keeps many harmful substances from entering the brain.
“In light of the chronic exposure of industry workers to DA, this study raises the troubling possibility of long-term neurological toxicity mediated by DA,” say the researchers.