Alzheimer's biomarkers can be found in eye fluid

The neurobiological hallmarks of Alzheimer’s disease are amyloid plaques and neurofibrillary tangles, both of which are specific neurological changes that occur in the brain at a microscopic level. This is why a diagnosis of Alzheimer’s disease can be so difficult in a living person: We can’t look at the brain under a microscope to check for plaques and tangles, which would be the only way to diagnose Alzheimer’s definitively. Currently, this can only occur by autopsy.

Recent imaging advances allow us to see the plaque buildup (amyloid) or tangles (tau) by way of an amyloid PET scan or tau PET scan, respectively. Amyloid PET scans are FDA-approved, but rarely ordered because insurance does not yet cover the procedure. Tau PET scans are used in research but have not yet been FDA-approved. Both procedures are costly and involve the injection of an isotope—a dye that binds to the amyloid or tau protein and lights up when the patient is in the scanner.

We can also measure for byproducts of plaques and tangles by looking in cerebrospinal fluid, the fluid that circulates in the brain and spinal cord. Insertion of a needle into the spinal cord allows for the withdrawal of fluid that can then be assayed, much like blood, for measures of specific components.

In unaffected individuals, amyloid levels in cerebrospinal fluid are high—an indication that amyloid is being cleared from the brain as it should be—and tau levels are low. For people with Alzheimer’s disease, the opposite is true: There are low levels of amyloid in cerebrospinal fluid and high levels of tau. Specific cutoff points for amounts of amyloid and tau to aid in diagnosis have not been fully standardized yet.

The quest for easily obtainable biological markers of Alzheimer’s disease is ongoing and far-reaching. Numerous groups are studying possibilities for blood markers. Genetic testing is also on the rise, but inconclusive because most forms of Alzheimer’s disease cannot be predicted by genes alone.

A group of researchers at Boston Medical Center recently reported that eye fluid may contain biological markers of Alzheimer’s disease. The researchers utilized eye fluid samples that would otherwise have been discarded from 80 patients who underwent eye surgery. They found that levels of amyloid and tau in eye fluid correlated with performance on a cognitive test: lower levels of these proteins correlated with lower cognitive test scores.

Correlation does not prove causation, so much more research needs to be done. In fact, there have been other groups who have advocated and studied the potential use of retinal examination for the presence of amyloid plaques. The premise is that the retina is an extension of the brain. Amyloid plaques in the brain have been correlated with amyloid plaque in the retina.

Experimental eye drops that stain for amyloid may be used with a medical device to detect the presence of amyloid plaque in the retina, which then may correlate with amyloid plaque in the brain. Such studies have also received media attention. And, another recently published study explores the relationship between dental gum plaque and brain plaque.

While none of these techniques is currently available for clinical use, as none have met the FDA criteria for approval, they are all a testament to the need for efficient, accessible diagnostic tools for Alzheimer’s disease. Time is brain and early diagnosis is critical to finding a cure. And, you never know, the answer could be more than what meets the eye.

For more information about Alzheimer’s disease diagnosis and access to potential treatments, please contact The CRCNJ at 973-850-4622.

MIT researchers used sound and light to decrease amyloid and tau in mouse brains

Hot off the press, researchers at MIT share their characteristic out-of-the-box approach to solving the underlying problem of Alzheimer’s disease. Leave it to the MIT braniacs to design a medical device that may treat Alzheimer’s AND do so by applying a relatively simple, known concept to a very complex puzzle.

Researchers at the Picower Institute for Learning and Memory are using 40 hertz (hz) signals, in different sensory modalities—light and sound—to help restore gamma activity in the brain. In a mouse model, the generation of gamma brain wave activity initiated by exposure to 40 hz light and sound stimulation resulted in a decrease in amyloid plaques and phosphorylated tau proteins—both hallmarks of Alzheimer’s disease—in different brain regions.

An old adage in the research community is: “We’ve cured a thousand mice, but if we could only cure one (wo)man….” That is the true test of a viable treatment. The utility and value of this medical device is currently being tested in humans and we, at The Cognitive and Research Center of New Jersey, have been selected as a site for this study, aMulti-Center Study of Sensory Stimulation to Improve Brain Function, also known as the Overture Study, sponsored by Cognito Therapeutics, Inc.

The Overture Study is a Phase I/II randomized, controlled, single-blind multi-center clinical trial using the GammaSense Stimulation device to study safety, adherence rates and efficacy in subjects with Alzheimer’s disease or Mild Cognitive Impairment due to Alzheimer’s disease. Eligible subjects must be 55 years or older, obtain a Mini-Mental Status Examination score of 14 to 26 and have someone who can serve as a study partner. People who have profound hearing or visual impairment, seizure disorder, implantable devices that prohibit MRIs, or who are taking memantine (Namenda or Namzaric) would not be eligible. Overall, the goal is to enroll a total of 60 subjects across sites.

Subjects who pass screening will be randomized at a ratio of 2:1 treatment to control, which means that each subject has about a 67 percent chance of receiving active treatment and a 33 percent chance of receiving placebo. Neither the participants nor the site raters will know whether a subject is on treatment or receiving a sham, as knowing treatment group could cause biases.

Subjects will be required to utilize the device at home for 60 minutes daily for six months. During that time, subjects and study partners will come to the site periodically to undergo various cognitive tests and scales of behavioral functioning. Subjects will also receive multiple amyloid positron emission tomography (PET) scans.

Contact us to learn more about the Overture study and whether you or a loved one are a candidate, as we are actively enrolling for this trial at The Cognitive and Research Center of New Jersey.