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New promising biomarker | Alzheimer’s disease

Dementia. Forgetfulness, losing track of time, getting lost in familiar places. Communication becomes more difficult, behavioral changes appear. In advanced stages of the disease, affected people are no longer aware of time and place. Later, they do not recognize even their closest friends and family members.

Currently, about 55 million people worldwide are living with dementia – and about 10 million new cases are added each year.

The best known and most widespread form of dementia is Alzheimer’s disease (AD). One cruel thing is that although Alzheimer’s can still be treated in the early stages before irreversible dementia, the disease is often not recognized until it is too late for treatment. And this is the reason: available diagnostic methods are expensive and not suitable for routine examinations for the general public. Therefore, new screening programs are needed.

In recent years, abnormal formaldehyde metabolism has been considered one of the essential features of age-related cognitive impairment, and urinary formaldehyde has been proposed as a potential biomarker for early diagnosis of AD. But this biomarker has limitations, and new methods are needed to improve disease detection and the delivery of appropriate therapies. So, how could this method be further improved?

A new study shows: Formic acid is suitable as a biomarker for early diagnosis of Alzheimer’s disease

A research group from China investigated the relationship between the level of formic acid (a metabolic product of formaldehyde) and cognitive changes in the course of Alzheimer’s disease, comparing the diagnostic effects of different biomarkers in plasma (e.g., Aβ40) and formic acid.

Methods: 574 Participants underwent cognitive function tests by trained staff in a neuropsychology assessment room. They were then divided into five groups according to the severity of their disease. Researchers collected morning urine samples and analyzed urine formaldehyde by high-pressure liquid chromatography. The levels of formic acid in collected urine samples were determined by the Formate Assay Kit.

Results: The study found that the more severe the Alzheimer’s disease had progressed, the higher the level of formic acid in a person’s urine. Especially in the early stages of the disease, formic acid was a much better indicator than any previously known biomarker tested in blood or urine. Combining biomarkers from blood and formic acid from urine could provide unprecedented accuracy about disease stage.

Advantages at a glance

  • Formic acid in urine showed excellent sensitivity for early Alzheimer’s screening

  • In general, urinary formic acid showed a unique efficacy in the diagnosis of Alzheimer’s disease

  • As a biomarker that can be measured via urine, formic acid detection is convenient and suitable for routine testing

  • Detection of Alzheimer’s biomarkers is cost-effective

Urinary formic acid levels showed higher usefulness than formaldehyde. Therefore, our study proved that the non-invasive and cost-effective urinary biomarkers improved the prediction accuracy of disease stages by plasma biomarkers.
Wang et al., 2022

As is customary, the researchers point to the need for further research, since the cross-sectional study cannot prove causality. Nevertheless, they are confident:

Urinary formic acid and formaldehyde are likely to be new biomarkers independent of the existing AD diagnostic criteria. 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.
Wang et al., 2022

You can read the study in the journal Frontiers here: https://www.frontiersin.org/articles/10.3389/fnagi.2022.1046066/full