The results of a study by a group from Shanghai Jiaotong University show that formic acid is a sensitive urine biomarker that can detect early Alzheimer’s disease (AD). The findings could pave the way for cheap and convenient mass screening. Dr. Yifan Wang, Dr. Qihao Guo and colleagues published an article titled “Systematic Evaluation of Formic Acid in Urine as a New Potential Alzheimer’s Biomarker” in Frontiers in Aging Neuroscience. In their statement, the authors concluded: “Formic acid in urine has excellent sensitivity for early screening for Alzheimer’s disease… Detection of biomarkers of Alzheimer’s disease in urine is convenient and economical. It should be included in the routine medical examination of the elderly.”
The authors explain that AD, the most common form of dementia, is characterized by progressive cognitive and behavioral impairment. The main pathological features of AD include abnormal accumulation of extracellular amyloid β (Aβ), abnormal accumulation of neurofibrillary tau tangles, and synapse damage. However, the team continued, “the pathogenesis of AD is not fully understood.”
Alzheimer’s disease can go unnoticed until it’s too late for treatment. “It is a persistent and insidious chronic disease, meaning it can develop and persist for many years before overt cognitive impairment appears,” the authors say. “The early stages of the disease occur before the stage of irreversible dementia, which is a golden window for intervention and treatment. Therefore, large-scale screening for early-stage Alzheimer’s disease in the elderly is warranted.”
While mass screening programs help to detect the disease at an early stage, current diagnostic methods are too cumbersome and expensive for routine screening. Positron emission tomography-computed tomography (PET-CET) can detect early Aβ deposits, but is expensive and exposes patients to radiation, while biomarker tests that help diagnose Alzheimer’s require invasive blood draws or lumbar punctures to obtain cerebrospinal fluid, which may be repulsive to patients.
The researchers note that several studies have shown that it is possible to screen patients for urinary biomarkers of AD. The urinalysis is non-invasive and convenient, making it ideal for mass screening. But while scientists have previously identified urinary biomarkers for AD, none are suitable for detecting early stages of the disease, meaning the golden window for early treatment remains elusive.
Wang and colleagues have previously studied formaldehyde as a urinary biomarker for Alzheimer’s disease. “In recent years, abnormal formaldehyde metabolism has been recognized as one of the main features of age-related cognitive impairment,” they say. “Our previous study reported a correlation between urinary formaldehyde levels and cognitive function, suggesting that urinary formaldehyde is a potential biomarker for the early diagnosis of AD.”
However, there is room for improvement in the use of formaldehyde as a biomarker for early disease detection. In their recently published study, the team focused on formate, a formaldehyde metabolite, to see if it works better as a biomarker.
The study group included 574 people, including patients with Alzheimer’s disease of varying severity, as well as cognitively normal healthy control participants. The researchers analyzed urine and blood samples from the participants to look for differences in urine biomarkers and conducted a psychological assessment. Participants were divided into five groups based on their diagnoses: cognitively normal (NC) 71 people, subjective cognitive decline (SCD) 101, no mild cognitive impairment (CINM), cognitive impairment 131, mild cognitive impairment (MCI) 158 people, and 113 with BA. .
The study found that urinary formic acid levels were significantly elevated in all Alzheimer’s disease groups and correlated with cognitive decline compared to healthy controls, including the early subjective cognitive decline group. This suggests that formic acid may serve as a sensitive biomarker for the early stage of AD. “In this study, we report for the first time that urinary formic acid levels change with cognitive decline,” they said. “Urine formic acid has shown unique efficacy in diagnosing AD. In addition, urinary formic acid was significantly increased in the SCD diagnosis group, which means that urinary formic acid can be used for early diagnosis of AD.”
Interestingly, when the researchers analyzed urine formate levels combined with blood Alzheimer’s biomarkers, they found they could more accurately predict the stage of the disease in patients. However, further research is needed to understand the link between Alzheimer’s disease and formic acid.
However, the authors concluded: “Urine formate and formaldehyde levels can not only be used to differentiate AD from NC, but also improve the predictive accuracy of plasma biomarkers for AD disease stage. potential biomarkers for diagnosis”.