Sleep Molecules May Represent a New Blood Biomarker for Earlier Diagnosis, Study Suggests

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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High blood levels of primary fatty acid amides (PFAMS), a class of fatty molecules involved in sleep and movement control, are associated with increased accumulation of beta-amyloid protein in the cerebrospinal fluid of patients with Alzheimer’s disease, a study finds.

Researchers believe that this class of fatty molecules may represent a new blood biomarker that can help physicians diagnose Alzheimer’s earlier.

The study, “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,” was published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

Alzheimer’s disease is a progressive neurodegenerative disorder characterized by the formation of plaques made of a protein called beta-amyloid. These protein clumps accumulate between nerve cells in the brain, disrupting their ability to communicate with each other and impairing their function. It is believed that these plaques start to form many years before the onset of the first Alzheimer’s symptoms, known as the preclinical phase of the disease.

“It is thought that one of the reasons for the failure of [therapy] candidates is that they were not administered during the preclinical phase of the disease. This introduces the challenge of diagnosing people during the preclinical phase of the disease, when they are cognitively normal. For this to be possible, it is necessary to discover biomarkers that can identify individuals at high risk of developing clinical Alzheimer’s disease,” the researchers said.

An international team, led by researchers from King’s College London, set out to look for molecules in the blood that could be linked to the presence of beta-amyloid deposits in the brain and the progression of Alzheimer’s.

They analyzed a total 593 blood samples collected from people with Alzheimer’s disease. Among these patients, 242 were cognitively healthy, 236 had mild cognitive impairments, and 115 had been diagnosed with dementia associated with Alzheimer’s.

The team evaluated the relationship between 883 different molecules that could be found in the blood samples and different clinical parameters, including cerebrospinal fluid markers (CSF, the liquid that circulates in the brain and spinal cord) of disease, data from magnetic resonance imaging (MRI), degree of cognitive impairment, and clinical diagnosis of Alzheimer’s.

From the hundreds of molecules that were evaluated in the blood screens, only nine were found to be associated with the levels of beta-amyloid or tau protein in the CSF. These included four PFAMS, two lipokines (lipid-controlling hormones), and three amino acids (the building blocks of proteins).

Among these identified biological molecules, PFAMS and the amino acids aspartate and glutamate were also found to be associated with patients’ memory and volume of the hippocampus — the brain region responsible for short-term memory.

“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,” Cristina Legido-Quigley, PhD, associate professor at King’s College London and lead author of the study, said in a press release.

Previous studies have suggested that these fatty molecules have neuroprotective activity and can induce sleep. Increasing evidence also has shown that amyloid clumps accumulate in the brain of people with lack of sleep. Taken together, these findings suggest that PFAMS “may be playing a role in clearing up toxic amyloid in the brain,” she said.

To develop new treatments for Alzheimer’s, it is necessary to have reliable diagnostic tests that could be used to identify people at risk. Based on this study’s findings, a simple blood test that could determine PFAMS levels may represent a cheaper and easier strategy to measure amyloid in the brain than a spinal tap.

“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,” she added.