June is Alzheimer’s Awareness Month, and a good time to learn more about this disease. It is now being said that earlier detection may be necessary for treatment. Given the lack of an accurate diagnostic test for Alzheimer’s disease (AD), treatment for the condition typically begins after the first signs of memory loss become evident.
Unfortunately, this may be too late.
In Alzheimer’s disease, extracellular amyloid plaques and intraneuronal neurofibrillary tangles develop in the brain, directly leading to problems with memory and cognition. The building blocks of these structures are beta-amyloid (amyloid-β; Aβ) peptides for plaques and tau for tangles. The two work together to drive healthy neurons into a diseased state.
To date, clinical trials assessing agents targeting either tau or amyloid-β peptide, such as a double-blind controlled study published in January 2016 in Alzheimer’s Research and Therapy, have yielded mixed results.
That’s why new findings by researchers from the lab of William Jagust, MD, the endowed chair in geriatric medicine at the University of California in Berkeley, may be a game changer in the development of new treatments for AD.
Their study, published online on April 23 by the Journal of Neuroscience, suggests that amyloid accumulation in the brain may already be slowing down by the time a person is considered to have “pre-clinical” AD (meaning: before mild cognitive impairment has been observed).
“Our findings suggest that the time window to intervene to slow Alzheimer’s disease progression may need to be even earlier than we expected,” says Stephanie Leal, PhD, a postdoctoral fellow in the Jagust Lab.
“Low and increasing levels of amyloid predict the later development of tau pathology, even in older adults who are considered ‘amyloid negative,’ which suggests that interventions may need to begin before pathology has a chance to spread and clinical symptoms manifest,” Dr. Leal says.
When to Begin Alzheimer’s Treatment Is an Open Question
Historically, deciding when to initiate treatment has been the biggest clinical challenge in the management of AD. Since the mid-2000s, research has focused on the role of amyloid and tau in the development of the condition, with the idea of using either or both as a means of assessing individual risk.
According to the working theory, those with elevated levels of the proteins would be diagnosed as “amyloid positive” and thus at risk for developing AD. So-called “anti-amyloid” therapy would be prescribed to slow AD progression, even before obvious cognitive decline has been observed.
While existing research evidence indicates that this approach may be on the right track, it has yet to produce an effective treatment for AD. According to Leal, the Jagust Lab findings demonstrate that anti-amyloid therapies would perhaps be more effective if they were administered even earlier, before those who are “amyloid positive” even reach pre-clinical AD, and long before the first signs of memory loss.
Earlier research in the Jagust Lab, published in the February 2017 issue of the journal eLife, concluded that increased amyloid levels in the brain resulted in “declining memory performance.”
“There have been many failures of phase 3 clinical trials of anti-amyloid therapies, which has raised the possibility that such trials begin too late, once the disease has exerted irreversible effects on the brain,” Leal says. “AD begins … decades before symptom onset, but it is unknown at what point it starts to exert harmful neurological effects.”
Researchers Probe Timeline of Brain Changes, Symptoms
For the latest research in the Jagust Lab, Leal and her colleagues assessed healthy men and women between the ages of 61 and 88 over a five-year period using PET scans. Results revealed that even trace amounts of beta-amyloid predicted future levels of tau in the study subjects, and both preceded memory decline.
In addition, they noted that greater baseline levels of beta-amyloid were associated with a faster rate of accumulation, at least initially. As the disease progressed, higher beta-amyloid levels were associated with slower accumulation.
“We are continuing to collect longitudinal data from the participants in our cohort in order to follow up on any changes in amyloid accumulation, tau accumulation, and how these pathologies are interacting to influence memory decline,” Leal says.
Source: https://www.everydayhealth.com/alzheimers-disease/earlier-detection-alzheimers-disease-may-necessary-treatment/