Detecting dementia in the blood

If the suspicion of Alzheimer's disease creeps up, those affected must prepare themselves for lengthy and complex procedures until the case is clear. A team from Empa and the Cantonal Hospital of St. Gallen is now in the process of developing a blood test that will enable a reliable diagnosis using atomic force microscopy (AFM). The researchers have recently published their first results of a successful pilot study in the journal Science Advances.

In the beginning, physicist Peter Nirmalraj wanted to understand the molecular pathogenesis of Alzheimer's in order to enable new approaches in diagnostics and therapy.

One step further would be to decipher the exact role of beta-amyloid peptides and tau proteins associated with the neurodegenerative disease.

In this project, the LHRC team plans to test whether flashing pulses of light at a frequency of 40 times per second, or 40 Hz, can not only increase "gamma" waves of electrical activity in the brains of patients but also counteract some of the problems associated with Alzheimer's disease. The team will also examine whether combining the 40-Hz flashes with a light therapy that is designed to reset a patient's sleep-wake cycle may also help.

Dr. Figueiro is part of team of researchers at Mount Sinai who are focused on understanding in great detail how light controls our health. For instance, the team has spent years developing light therapies to help nurses overcome fatigue and other negative effects of working overnight in dimly light environments. "One of the difficulties of modern times is that we have deprived ourselves of the daily doses of natural light that we need to maintain a healthy lifestyle," said Mark S. Rea, PhD, Associate Director of the LHRC.

Initially, the study will involve dozens of Mount Sinai patients who are diagnosed with early-stage Alzheimer's disease or mild cognitive impairment, a disorder that often precedes Alzheimer's. The light pulses will be delivered by a custom-made device, such as a box or goggles, developed at the LHRC. The results will be compared to those obtained from age-matched control subjects.

Gamma brain wave activity is associated with learning and memory. Studies in humans have suggested that the activity is reduced in Alzheimer's patients. Meanwhile, studies on mice that were genetically engineered to mimic certain aspects of the disease showed that flashing light at 40 Hz enhanced gamma activity while reducing neural cell death and the accumulation of beta-amyloid, a hallmark of Alzheimer's disease.To test out the role that sleep-wake cycles may have in this process, the team will expose patients to daily, high doses of daytime light that are designed to help patients sleep better.

About 40 percent of Alzheimer’s disease patients experience sleep-related problems, including agitation and daytime sleepiness. Studies that tested light therapies to treat these symptoms have so far produced mixed results. For this study, the sleep-wake cycle light will be delivered by either the same custom-made device used for flashing light or a different one, such as a table or lamp, which will allow for well-defined periods of constant daily exposure. Its effectiveness at counteracting the sleep and cognitive problems associated with Alzheimer's disease will be tested alone and in combination with the 40-Hz pulses.

"Our sleep-wake cycles play a critical role in brain health," Dr. Figueiro said. “By using a rigorous, two-pronged approach to light therapy it is possible that we could push the brains of Alzheimer's patients into a healthier state."

This study, entitled “The Use of Rhythmic Light Therapy to Entrain Gamma Oscillations and the Circadian System in Patients with Alzheimer's Disease and Related Dementias (ADRD)” will be funded by the National Institutes of Health.