Towards Reliable, Low-Cost Tests for the Earliest Stages of Alzheimer's Disease

The research community has moved quite determinedly these past few years towards practical, low-cost tests for early Alzheimer's disease. Even with the limited means available to patients today, an early warning might be used to delay the aggregation of amyloid-β that takes place in the initial stages of the condition, before the appearance of cognitive impairment. Lifestyle changes such as weight loss and improved fitness, antiviral therapies, and control of chronic inflammation should all make some difference, given what is known of the mechanisms of Alzheimer's disease. Looking ahead, better options may soon be available. Senolytics, for example, may make a difference. Further, as means of directly reducing amyloid-β levels in the aging brain are starting to emerge, finally, these therapies might be better applied in the early stages of the condition, rather than later, when the disease process is beyond their ability to control.

Early treatment through the clinical community requires some form of early diagnosis - so early treatment is very dependent on the existence of standard, widely accepted tests that can be readily and cheaply applied. While it is certainly possible to assess amyloid-β in cerebrospinal fluid, and has been for many years, that requires a lumbar puncture. It is expensive, painful, and certainly not the sort of thing people would willingly undergo once a year. Today's selection of research results from recent months covers a number of lines of work in which researchers are making progress towards an improved set of tests that might determine progression towards Alzheimer's disease.

Blood test detects Alzheimer's damage before symptoms

A simple blood test reliably detects signs of brain damage in people on the path to developing Alzheimer's disease - even before they show signs of confusion and memory loss. The test detects neurofilament light chain, a structural protein that forms part of the internal skeleton of neurons. When brain neurons are damaged or dying, the protein leaks out into the cerebrospinal fluid that bathes the brain and spinal cord and from there, into the bloodstream.

Finding high levels of the protein in a person's cerebrospinal fluid has been shown to provide strong evidence that some of their brain cells have been damaged. But obtaining cerebrospinal fluid requires a spinal tap, which many people are reluctant to undergo. Here, researchers studied whether levels of the protein in blood also reflect neurological damage. To find out whether protein blood levels could be used to predict cognitive decline, the researchers collected data on 39 people with disease-causing variants when they returned to the clinic an average of two years after their last visit. The researchers found that people whose blood protein levels had previously risen rapidly were most likely to show signs of brain atrophy and diminished cognitive abilities when they revisited the clinic. "It will be important to confirm our findings in late-onset Alzheimer´s disease and to define the time period over which neurofilament changes have to be assessed for optimal clinical predictability."

New discoveries predict ability to forecast dementia from single molecule

A new study shows that harmful single tau molecules take different shapes that each correlates to a distinct type of larger assembly that will form and self-replicate across the brain. Researchers had already established that the structure of larger tau assemblies determines which type of dementia will occur - which regions of the brain will be affected and how quickly the disease will spread. But it was unknown what specified these larger structures. The new research reveals how a single tau molecule that changes shape at the beginning of the disease process contains the information that determines the configuration of the larger, toxic assemblies. This finding suggests that characterization of the conformation of single tau molecules could predict what incipient disease is occurring - Alzheimer's or other types of dementia.

The team is trying to translate these findings into clinical tests that examine a patient's blood or spinal fluid to detect the first biological signs of the abnormal tau, before the symptoms of memory loss and cognitive decline become apparent. The researchers are also working to develop treatments to stabilize shape-shifting tau molecules, prevent them from assembling, or promote their clearance from the brain.

A biomarker in the brain's circulation system may be Alzheimer's earliest warning

The blood-brain barrier is a filtration system, letting in good things (glucose, amino acids) and keeping out bad things (viruses, bacteria, blood). It's mostly comprised of endothelial cells lining the 400 miles of arteries, veins, and capillaries that feed our brains. Some evidence indicates that leaks in the blood-brain barrier may allow a protein called amyloid into the brain where it sticks to neurons. This triggers the accumulation of more amyloid, which eventually overwhelms and kills brain cells.

"Cognitive impairment, and accumulation in the brain of the abnormal proteins amyloid and tau, are what we currently rely upon to diagnose Alzheimer's disease, but blood-brain barrier breakdown and cerebral blood flow changes can be seen much earlier. This shows why healthy blood vessels are so important for normal brain functioning." Blood-brain barrier leaks can be detected with an intravenously administered contrast substance in concert with magnetic resonance imaging. Brain microbleeds, another sign of leakage, also can be picked up with MRI. A slowdown in the brain's uptake of glucose, visible via PET scan, can be a another result of blood-brain barrier breakdown.

Scientists pave the way for saliva test for Alzheimer's disease

Researchers examined saliva samples from three sets of patients, those with Alzheimer's disease, those with mild cognitive impairment, and those with normal cognition. Using a powerful mass spectrometer, they examined more than 6,000 metabolites - compounds that are part of our body's metabolic processes - to identify any changes or signatures between groups. "In this analysis, we found three metabolites that can be used to differentiate between these three groups. This is preliminary work, because we've used a very small sample size. But the results are very promising. If we can use a larger set of samples, we can validate our findings and develop a saliva test of Alzheimer's disease. So far, no disease-altering interventions for Alzheimer's disease have been successful. For this reason, researchers are aiming to discover the earliest signals of the disease so that prevention protocols can be implemented."


Apart from that, this can make the finding of suitable patients for trials more cheaper.

Posted by: Antonio at January 26th, 2019 10:12 AM

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