Simple blood test may help early diagnosis of Alzheimer’s

posted on 05/03/2022 06:00

  (credit: OLIVER BUNIC)


(credit: OLIVER BUNIC)

A blood test can identify the risk of developing Alzheimer’s disease early, increasing the chances of delaying or alleviating symptoms with the adoption of a healthy lifestyle. While there is still no cure for the neurodegenerative disease, several studies suggest that mind and body care, such as exercise, a low-fat diet, and social engagement, can delay cognitive signs.

Now, a study from the University of California, San Diego, shows that excess of an enzyme in the blood is present in Alzheimer’s patients even before the first manifestations of the disease appear.

The research, which confirms an earlier finding by the same group of scientists, was published in the journal Cell Metabolism. According to the authors, in addition to indicating the possibility of predicting the disease early, the results suggest that dietary supplementation with the amino acid produced by the substance is not a good idea.

Sheng Zhong, who led the study, explains that previous research has stimulated the belief that supplements containing serine, produced by the PHGDH gene, could contribute to fighting Alzheimer’s. As the substance is essential for brain metabolism, some scientists have tested, in animals, whether the amino acid deficiency was linked to cognitive degenerations characteristic of the disease. Some results indicated that rodents lacking the substance, in fact, exhibit behaviors consistent with the disease.

However, in the current study, carried out with human brain tissue, Zhong, Xu Chen and Riccardo Clandrelli, co-authors of the article, found that individuals who had Alzheimer’s actually exhibited an increased expression of PHGDH. According to them, this suggests that, rather than serine production being deficient in the disease, it would actually be excessive. “Anyone who wants to recommend or take serine to mitigate Alzheimer’s symptoms should exercise caution,” says Calandrelli.

two years before

Two years ago, the team from Zhong’s lab announced, also in Cell Metabolism, the first results indicating that PHGDH may be a safe biomarker for Alzheimer’s. At the time, scientists did blood tests on the elderly and found that, in those with the disease, the enzyme levels were higher up to two years before they were diagnosed.

“A number of known changes associated with Alzheimer’s disease usually show up around the time of clinical diagnosis, which is a little too late. We had a hunch that there was a molecular predictor that would show up years earlier, and that’s what motivated us,” says Zhong.

The promising results stimulated the continuation of the study. The scientists’ hunch was that the change in the blood had something to do with the brain. Now, they’ve analyzed genetic information extracted from post-mortem brain tissue in four different surveys, each of which was carried out with 40 to 50 individuals over the age of 50.


Bioengineer at the University of California Sheng Zhong

Bioengineer at the University of California Sheng Zhong
(Photo: UCSD/Disclosure)

The assessments were divided into groups: healthy people (control) and asymptomatic people (without cognitive problems or a diagnosis of Alzheimer’s, but with changes in brain tissue that indicate early signs of the disease). The results showed that, in the latter, there was a significant increase in the enzyme PHGDH, compared to those who neither exhibited changes in the brain nor had been diagnosed with the disease.

Another finding is that, as in laboratory-tested mouse models, PHGDH expression levels were higher the more advanced the disease. In humans, the scientists made this finding by comparing the amount of the enzyme in the blood of patients diagnosed with Alzheimer’s with the scores they obtained in two different clinical assessments. One classifies memory and cognitive ability, while the other investigates disease severity based on brain pathology.

The results of the University of California team showed that the worse the scores, the greater the brain expression of PHGDH. “The fact that the level of expression of this gene directly correlates with a person’s cognitive ability and disease pathology is remarkable. Being able to quantify these two complex metrics with a single molecular measure could make diagnosis and monitoring of Alzheimer’s disease progression much simpler.”

Management

For neurologist Rosa Sancho, head of the research department at Alzheimer’s Research UK, in the United Kingdom, a future blood test for early detection could be very useful for the management of the disease. “We know that the brain changes in Alzheimer’s disease can occur decades before symptoms start to appear, and the early stages of the disease are likely to be the time when future drugs are most effective,” she says.

While acknowledging that tests like this won’t be available immediately, Sancho says he’s confident. “Currently, people are only diagnosed with Alzheimer’s when symptoms appear. Many of the diagnostic tools that can detect early changes are either expensive, such as brain scans, or invasive, such as spinal fluid tests. A reliable blood test would be a great help.” boost for dementia research, allowing scientists to test treatments at a much earlier stage, which in turn could lead to a breakthrough for those living with dementia.”

Broken brain connections

The early diagnosis of Alzheimer’s is also studied by researchers at Massachusetts General Hospital, USA, focusing on other substances associated with the disease: beta-amyloid and tau proteins.


LEG scans show changes in the brain of an Alzheimer's patient (d), compared to a healthy person (e)

LEG scans show changes in the brain of an Alzheimer’s patient (d), compared to a healthy person (e)
(photo: AFP)

When accumulated in the brain, they disrupt connections between structures important for cognition. In a study published in the journal Proceedings of the National Academy of Sciences, scientists found that these interactive changes may be present before the first signs of the disease appear.

For years, researchers have known that excess beta-amyloid and tau dysfunction can cause neuron death. “But we didn’t know how the brain’s connections respond to the accumulation of these proteins very early in the disease process, even before symptoms,” Yakeel Quiroz, senior author of the paper, explained in a note.

To learn more about this phenomenon, Quiroz studied positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) scans of more than 6,000 patients in Antioquia, Colombia, who have a genetic form of the disease, caused by the mutation E280A. These people develop the first signs of cognitive impairment very early, at age 44, and reach dementia at just 49.

In the study, participants with the genetic alteration did not yet show signs of the disease. Previously, the same team showed that these individuals exhibit high levels of beta-amyloid nearly two decades before the onset of symptoms and changes in tau around the previous six years. Now, scientists have observed, with imaging tests, the connectivity within and between different brain networks, made up of millions of cells.

Resonance

The researchers found that mutation carriers had connection disruptions in the brain’s main memory network years before the onset of cognitive impairment. They also developed a new mathematical approach that combines MRI information with molecular imaging to see more clearly when brain regions begin to disconnect during the disease process.

“This finding improves our understanding of how pathology related to Alzheimer’s disease alters the functional organization of the brain years before cognitive impairment occurs,” said Quiroz. “These are important findings because they also suggest that MRI could be used, in the future, to identify people who may already have pathology in their brain, although more research is still needed.”

  • Bioengineer at the University of California Sheng Zhong

    Bioengineer at the University of California Sheng Zhong
    Photo: UCSD/Disclosure

  • LEG scans show changes in the brain of an Alzheimer's patient (d), compared to a healthy person (e)

    LEG scans show changes in the brain of an Alzheimer’s patient (d), compared to a healthy person (e)
    Photo: AFP

Broken brain connections

  (credit: AFP)


credit: AFP

The early diagnosis of Alzheimer’s is also studied by researchers at Massachusetts General Hospital, USA, focusing on other substances associated with the disease: beta-amyloid and tau proteins. When accumulated in the brain, they disrupt connections between structures important for cognition. In a study published in the journal Proceedings of the National Academy of Sciences, scientists found that these interactive changes may be present before the first signs of the disease appear.

For years, researchers have known that excess beta-amyloid and tau dysfunction can cause neuron death. “But we didn’t know how the brain’s connections respond to the accumulation of these proteins very early in the disease process, even before symptoms,” Yakeel Quiroz, senior author of the paper, explained in a note.

To learn more about this phenomenon, Quiroz studied positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) scans of more than 6,000 patients in Antioquia, Colombia, who have a genetic form of the disease, caused by the mutation E280A. These people develop the first signs of cognitive impairment very early, at age 44, and reach dementia at just 49.

In the study, participants with the genetic alteration did not yet show signs of the disease. Previously, the same team showed that these individuals exhibit high levels of beta-amyloid nearly two decades before the onset of symptoms and changes in tau around the previous six years. Now, scientists have observed, with imaging tests, the connectivity within and between different brain networks, made up of millions of cells.

Resonance

The researchers found that mutation carriers had connection disruptions in the brain’s main memory network years before the onset of cognitive impairment. They also developed a new mathematical approach that combines MRI information with molecular imaging to see more clearly when brain regions begin to disconnect during the disease process.

“This finding improves our understanding of how pathology related to Alzheimer’s disease alters the functional organization of the brain years before cognitive impairment occurs,” said Quiroz. “These are important findings because they also suggest that MRI could be used, in the future, to identify people who may already have pathology in their brain, although more research is still needed.” (DUST)

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