Alzheimer’s disease (AD) is a particularly troubling neurodegenerative disease. Not only is there is no decent way to slow the progression of the disorder, but there is also currently no definitive diagnostic test for AD. While clinicians have become good at diagnosing the disorder based on an array of test results, there are a plethora of neurological conditions that have overlapping symptoms with AD, confounding the diagnostic process.
Now, a new study from investigators at King’s College London describes how a particular class of molecules could be used as biomarkers to help with diagnosing AD. The research team found that the level of fatty molecules in the blood belonging to the endocannabinoid pathway—which may also help induce sleep—were higher in those participants in the study with amyloid in the brain. Findings from the new study were released today in Alzheimer’s & Dementia through an article titled “Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer’s Disease biomarker discovery cohort.”
“This is the first study in which lipid molecules produced in the brain are found in the blood, as amyloid deposition increases in Alzheimer’s disease,” says senior study investigator Cristina Legido-Quigley, PhD, a senior lecturer in King’s College London Institute of Pharmaceutical Science. “These fatty amides are known to be neuroprotective and to induce sleep. There is also evidence that amyloid accumulates in the brain with lack of sleep, so these molecules may be playing a role in clearing up toxic amyloid in the brain.”
Previous work on AD has established that the amyloid peptide goes onto form plaques in the brain that is toxic to nerve cells. Plaque accumulation is thought to start many years before the appearance of symptoms such as memory loss. Drugs that have been developed so far to target amyloid have not been successful in restoring memory.
To investigate whether any molecules in blood could be linked to amyloid in the brain, researchers used a technique akin to throwing a big fishnet to catch as many molecules as possible in the blood. They then generated a list of hundreds of molecules and found that fatty acid amides increased in line with amyloid in the brain. The team also found that these molecules were connected to brain shrinkage and memory loss.
“This study analyzed 593 plasma samples selected from the European Medical Information Framework for Alzheimer’s Disease Multimodal Biomarker Discovery study, of individuals who were cognitively healthy (n=242), had mild cognitive impairment (n=236), or had AD-type dementia (n=15),” the authors write. “Logistic regressions were carried out between plasma metabolites (n=883) and CSF markers, magnetic resonance imaging, cognition, and clinical diagnosis.”
Interestingly, the metabolomic analysis enabled the researchers to find a number of molecules that were associated with well-known AD proteins.
“Eight metabolites were associated with amyloid β and one with t-tau in CSF, these were primary fatty acid amides (PFAMs), lipokines, and amino acids,” the authors state. “From these, PFAMs, glutamate, and aspartate also associated with hippocampal volume and memory.”
The investigators were excited by their findings, but understand that there is much more work that needs to be done before these molecules can be called definitive biomarkers for AD.
“A much-needed pre-requisite for new treatments for Alzheimer’s disease is a reliable diagnostic test that could be used to identify people at risk. A blood test would be cheaper than measuring amyloid in the brain and easier to do than a spinal tap,” Legido-Quigley concludes. “There is more work to be done. So far, we have measured these molecules in nearly 600 participants, and hope to expand to the thousands to establish if a new diagnostic test in blood is indeed possible.”
