Metabolic Biomarker Panel Shows Promise for Diagnosis of Dementia

A biomarker panel based on five groups of metabolites was shown to be potentially useful for diagnosis and therapy of various forms of dementia, such as Alzheimer’s disease.

Dementia, which is caused by factors that damage neurons, is characterized by a slowly progressing, chronic, and usually irreversible decline in cognitive function. The exact cause of neuron damage, and methods for its detection and treatment have remained elusive.


To rectify this situation, investigators at the Okinawa Institute of Science and Technology (Japan) employed nontargeted liquid chromatography–mass spectroscopy (LC-MS) to quantify small molecular markers in whole blood samples taken from of dementia patients. For this study, the investigators exhaustively analyzed blood samples collected from eight patients with dementia, from eight healthy elderly individuals, and from eight healthy young individuals. Overall, the investigators measured the levels of 124 different metabolites for each patient.

Analysis of the results revealed that 33 metabolites, classified into five groups (A to E), differed significantly in dementia patients, compared with healthy elderly subjects. Seven Group A metabolites present in plasma, including quinolinic acid, kynurenine, and indoxyl-sulfate, increased. The investigators suggested that these compounds may act as neurotoxins, damaging the central nervous system.

The remaining 26 compounds (in groups B to E) decreased in dementia patients, possibly causing a loss of support or protection of the brain in dementia. These compounds were thought to protect the nervous system against oxidative stress, maintain energy reserves, supply nutrients and act as neuroprotective factors.

“Identification of these compounds means that we are one step closer to being able to molecularly diagnose dementia,” said senior author Dr. Mitsuhiro Yanagida, head of the G0 Cell Unit at the Okinawa Institute of Science and Technology. “It is still too early to say, but it could suggest a possible mechanistic cause of dementia as these compounds may lead to impairment of the brain. In the future, we hope to start some intervention studies, either by supplementing dementia patients with metabolic compounds in sub-groups B-E, or by inhibiting the neurotoxins from sub-group A, to see if that can slow, prevent, or even reverse symptoms of dementia.”

The dementia study was published in the September 14, 2021, online edition of the journal Proceedings of the National Academy of Sciences of the United States of America.

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Okinawa Institute of Science and Technology