A recently identified biomarker found in urine could be the first step toward the development of a simple and inexpensive test for early-stage Alzheimer’s disease (AD), new researchers suggests.

Investigators found that levels of formic acid, a metabolic product of formaldehyde found in urine, were significantly higher in individuals with AD, including those with subjective cognitive decline, which may indicate very early stages of the disorder.

“Urinary formic acid and formaldehyde are likely to be new biomarkers independent of the existing AD diagnostic criteria,” Yifan Wang, Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China, and colleagues write.

“We believe that further research can determine the best diagnostic models using urinary formic acid and formaldehyde levels to significantly improve the diagnostic efficiency of urine biomarkers in AD,” they add.

The findings were published online November 30 in Frontiers in Aging Neuroscience.

Strong Correlation

The new study builds on the researchers’ earlier work that showed a correlation between urinary formaldehyde levels and cognitive function.

For this effort, they collected blood and urine samples from 574 individuals in Shanghai who had normal cognition (n = 71), subjective cognitive decline (n = 101), mild cognitive impairment (MCI, n = 158), cognitive impairment without MCI (n = 131), and AD (n = 113).

All participants underwent a battery of neurologic tests and some also underwent PET scans.

Compared with the group with normal cognition, urinary formic acid levels were significantly higher in each of the four other patient groups (P for all < .05).

Overall, urinary formic acid levels were slightly lower in the group with cognitive impairment without MCI compared with those who had subjective cognitive decline, MCI, and AD. However, the difference was not statistically significant.

Urinary formaldehyde levels were significantly higher in patients with AD compared with those who had normal cognition (P < .05), but were similar between other groups.

Researchers also compared formic acid and formaldehyde levels across different AD stages and found significantly higher levels across all stages compared with people who had no cognitive decline. Levels were also higher in patients with AD than in patients with MCI and those with cognitive impairment and no MCI, as well as in those with poorer neurologic test scores.

Among participants with PET scan data, higher levels were noted in those with abnormal accumulation of extracellular beta-amyloid.

“Important First Step”

Commenting for Medscape Medical News, Rebecca Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association and a member of the association’s Global Biomarker Standardization Consortium, said the study is the latest in a growing body of work seeking to identify reliable AD biomarkers.

“This is maybe the first paper, to my knowledge, that’s even going after this biomarker,” Edelmayer said. “It’s not ready to be used as a biomarker today, as there’s much more research that is going to be needed. But it’s an important first step.”

The investigators note that future studies would need to include a larger, more diverse study sample and PET imaging information on all participants.

Edelmayer added that questions also remain about how urinary formic acid stacks up to established biomarkers and how a urine test would compare to gold standard diagnostic tools, such as PET imaging; and reproducibility will be key.

Still, she noted that it’s good to see new developments in the field of biomarker identification and development.

“We need these types of fluid biomarkers because they will probably improve upon the patient journey and process for individuals throughout the health system as they seek a diagnosis, treatments, and appropriate care pathways and because they are more accessible, cost-effective, not invasive, and something that’s reliable and scalable around the globe,” Edelmayer said.

“There’s a real need for tools like this,” she added.

The study was funded by the National Natural Science Foundation of China, Shanghai Municipal Science and Technology Major Project, ZJLab the Guangdong Provincial Key S&T Program, and the Shanghai Pujiang Program. The investigators and Edelmayer report no relevant financial relationships.

Front Aging Neurosci. Published online November 30, 2022. Full text

Kelli Whitlock Burton is a reporter for Medscape Medical News covering neurology and psychiatry.

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