Urine biomarker may reveal early-stage Alzheimer’s disease, study shows

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A study showing that formic acid in urine may be an early biomarker for Alzheimer’s disease could pave the way for the development of more-accessible tests for the disease.

Findings from the study, entitled “Systematic evaluation of urinary formic acid as a new potential biomarker for Alzheimer’s Disease,” were published Wednesday in Frontiers in Aging Neuroscience.

The early detection of Alzheimer’s disease (AD) is critical for intervention and treatment before disease processes result in irreversible dementia. With the worldwide demographic growth of the elderly population, there is a need for more widespread screening for the disease.

At present, early detection of AD relies on PET scans and assessing levels of plasma biomarkers. However, PET scans are costly and access to PET is limited, while plasma biomarker analysis requires invasive lumbar punctures and blood draws -- disadvantages that render these procedures less feasible for routine screening programs, especially on a widespread level.

If one could be successfully developed and commercialized, a urine-based test for the early Alzheimer’s detection has the potential to be inexpensive, noninvasive, widely accessible, and considerably easier to deploy in routine screening than current methods.

In the study, academic researchers based in Shanghai and Beijing investigated the relationship between urinary formic acid and plasma biomarkers in Alzheimer’s, using a cohort of 574 participants sorted into groups depending on level of cognitive decline or impairment, from those with normal cognitive ability to those diagnosed with Alzheimer’s. Formic acid is a metabolic product of formaldehyde, the abnormal metabolism of which has recently been shown to be correlated with age-related cognitive decline.

The findings showed that the levels of formic acid as well as formaldehyde in urine increased with cognitive decline, and that the increase in formic acid was more consistent in its upward trend in parallel with increasing cognitive decline than conventional biomarkers. Additionally, urinary formic acid levels were significantly correlated with scores on the standard cognitive assessments administered to the participants. This correlation of formic acid with level of cognitive decline included the early-stage subjective cognitive decline group -- those most likely to be in the earliest stage of AD.

Furthermore, the study findings showed that integrating urinary formic acid and formaldehyde levels into the analysis of plasma biomarker levels improved accuracy in determining the stage of the disease, with formic acid levels showing greater benefit in this manner than those of formaldehyde.

The researchers acknowledged that there were some limitations to their study. The results do not demonstrate causality, and any conclusions drawn about the metabolic activity of formaldehyde and formic acid currently occupy the realm of the theoretical. Furthermore, the authors point out that PET data was limited in the study, especially in the group with normal cognition, as those participants were generally unwilling to expose themselves to radiation and contrast medium unnecessarily. Nevertheless, they write, further research may overcome these limitations, especially with larger studies.

“The pathogenesis of AD is not fully understood,” the authors said in the study. “What can be determined from current research is that AD is a continuous and concealed chronic disease, meaning AD can develop and last for many years before the emergence of evident cognitive impairment. The entire course of AD is divided into prodromal, preclinical, and dementia stages. Progression from subjective cognitive decline (SCD) to mild cognitive impairment (MCI) occurs before the irreversible dementia stage of AD, and this is the golden window for intervention and treatment.”

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