A Simple Urine Test for Alzheimer’s Disease?

A new study published in Frontiers in Aging Neuroscience identifies formic acid as a potential biomarker for early-stage Alzheimer’s disease. Obtained from urine, the biomarker could offer an inexpensive and efficient diagnostic tool for the neurodegenerative condition.

Diagnosing Alzheimer’s disease   

A diagnosis of Alzheimer’s disease requires a series of clinical assessments, such as interviews, cognitive and neuropsychological tests, which can prove expensive and unsuitable for large-scale routine screening. Many patients are diagnosed later in life when the disease has progressed beyond the reach of effective treatment. “Alzheimer’s disease is a continuous and concealed chronic disease, meaning that it can develop and last for many years before obvious cognitive impairment emerges,” say the authors of a new study exploring whether a simple urine test could offer a solution. “The early stages of the disease occur before the irreversible dementia stage, and this is the golden window for intervention and treatment. Therefore, large-scale screening for early-stage Alzheimer’s disease is necessary for the elderly.”

The researchers – a collaborative team from several institutes across China – conducted a study of 574 participants divided according to their cognitive status: normal cognitive (71), subjective cognitive decline (101), cognitive impairment without mild cognitive impairment (131), mild cognitive impairment (158) and Alzheimer’s disease (113). Previously, the scientists had examined the levels of formaldehyde in patients’ urine with Alzheimer’s disease, identifying a correlation. In this study, they focused on measuring levels of formic acid – a product of formaldehyde – as a potential biomarker for early disease detection.

The study found that urinary formic acid levels were significantly increased in all the Alzheimer’s groups compared with the healthy controls, including the early-stage subjective cognitive decline group, and correlated with a cognitive decline. This suggests that formic acid could act as a sensitive biomarker for early-stage Alzheimer’s disease.

Urinary formic acid levels correlate with cognitive decline

Urinary formic acid levels were significantly elevated in the Alzheimer’s groups compared to healthy controls, including participants with early-stage subjective cognitive decline. “Urinary formic acid was significantly correlated with Mini-Mental State Examination (MMSE) scores, the Chinese version of Addenbrooke’s Cognitive Examination III (ACE-III) scores and Montreal Cognitive Assessment-Basic (MoCA-B) time,” the researchers write in the publication.

When urinary formic acid levels were analyzed alongside blood-based Alzheimer’s disease biomarkers, the scientists found that they could more accurately estimate the stage of a patient’s disease. “Urinary formic acid showed an excellent sensitivity for early Alzheimer’s screening,” say the authors. Further study will be required to corroborate the data, but the research team are encouraged by their initial results: “The detection of urine biomarkers of Alzheimer’s is convenient and cost-effective, and it should be performed during routine physical examinations of the elderly,” they conclude.

Reference: Wang Y, Wang Y, Zhu J, et al. Systematic evaluation of urinary formic acid as a new potential biomarker for Alzheimer’s disease. Front. Aging Neurosci. 2022;14. doi: 10.3389/fnagi.2022.1046066.

This article is a rework of a press release issued by Frontiers. Material has been edited for length and content.