posted on 01/11/2023 06:00
(credit: KIRSTY WIGGLESWORTH)
The appearance of characteristic Alzheimer’s symptoms, such as poor memory and aggression, usually indicate that the patient is no longer in an early stage of the disease. Creating approaches that help detect this neurodegenerative process at an early stage is, according to scientists and other professionals in the field, essential to develop mechanisms capable of stopping it. Researchers at the Karolinska Institute in Sweden are betting that a blood test could provide this strategic information.
In an article published in the journal Brain, they show how biomarkers in the blood indicate the occurrence of early pathological changes in an inherited form of the disease. Researchers noticed changes in glial fibrillary acid protein (GFAP) about 10 years before the first symptoms of Alzheimer’s appeared.
“They were followed by increased concentrations of P-tau181 (tau protein) and, subsequently, NfL (neurofilament light protein), which we already know are directly associated with the extent of neuronal damage in the Alzheimer’s brain “explains Caroline Graff, one of the study authors and a professor in the Department of Neurobiology, Science and Society of Care at the Swedish institute.
To arrive at the result, the team analyzed 164 blood plasma samples from 33 people with a mutation that increases vulnerability to Alzheimer’s and 42 relatives without the hereditary pathogenic predisposition. The data was collected between 1994 and 2018, and the analysis indicated “clear changes” of various blood protein concentrations in mutation carriers a decade before the onset of symptoms.
In the team’s evaluation, the results hold promise for the development of new approaches against the disease. “In the future, the study results could be used as a non-invasive biomarker for the early activation of immune cells such as astrocytes in the central nervous system, which could be useful for the development of new drugs and for the diagnosis of cognitive diseases”, indicates Charlotte Johansson, a member of the research group.
Alzheimer’s is the most common type of dementia – data from the Swedish Brain Foundation shows it accounts for 60% to 70% of cases – and it starts to develop silently. According to the paper’s authors, biological changes in the brain begin 20 to 25 years before memory loss and other cognitive symptoms become apparent.
Nerve cells in the region degenerate due to the abnormal accumulation of amyloid-beta and tau proteins. As more brain neurons are damaged, this manifests itself in the dysfunction of cognitive functions such as memory and speech, the scientists explain. The sooner the complication is discovered, the better the chances of dealing with it. “This is one of the many reasons why more research into accurate and easy methods of early diagnosis is needed,” they said in a statement.
Expert in cognitive and behavioral neurology, Carlos Enrique Uribe says the strategy of looking for markers and signs that anticipate a person’s risk of having Alzheimer’s has mobilized scientists for many years. In the case of the Swedish work published in the latest issue of Brain, the originality lies in the fact that the investigation directly “affected” the disease.
For Uribe, this could be a path towards strategies that cure the disease. “By trying to find the source of the problem, it is possible to change its natural history. This strategy works to arrive at a healing procedure, changing the pathophysiological mechanism of the disease. In medicine, we call this disease-modifying treatment, and this did not exist yet in Alzheimer’s,” he says.
Uribe makes reservations. He recalls that the study analyzed patients with Alzheimer’s linked to genetic factors. “Because it’s not the most common case, these results need to be evaluated carefully, because genetically determined disease is a model for studying sporadic disease (without hereditary factors). Sometimes things just don’t work out with this direct relationship,” he explains. .
Cognitive neurology and dementia syndrome specialist Arthur Jatobá says there are some biomarkers available for early diagnosis of Alzheimer’s, but not for the general population. “Diagnosis today, for most patients, is made by clinical, neuropsychological evaluation, and brain imaging tests (cranial magnetic resonance imaging),” he says.
The doctor’s expectation is that, in the future, this type of analysis will be more accessible and will cover different biological indicators of increased risk. “I believe that, in the coming years, we will be able to do a blood test with a panel of different biomarkers for Alzheimer’s, such as amyloid beta protein, tau, GFAP and NfL. This will help us in the early diagnosis of the disease “, it is read.
even more vulnerable
“What’s interesting about this methodology of using people with genetically determined Alzheimer’s is that they have a much higher risk of developing symptoms. That’s why a lot of studies in the area are being done in this type of population. You know the problem is going to happen.” So monitor, identify what the marker was, and think about an intervention that can change that outcome, so the outcomes matter.”
Carlos Enrique Uribe, specialist in cognitive and behavioral neurology
The clinical picture of the stages of Alzheimer’s disease is divided into four stages, according to the Ministry of Health. In the former, there are usually changes in memory, personality, and visual and spatial skills. In the second, difficulty speaking, performing simple tasks, coordinating movements, restlessness and insomnia. Thus, resistance to carrying out daily activities, urinary and faecal incontinence, difficulty eating and progressive motor impairment. Finally mutism, pain on swallowing and intercurrent infections.
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