Source: Bio Valley
What is the effect of "synaptic loss"? For 30 years, scientists have believed that synapse loss (the loss of connections between brain cells) is a major pathologically relevant factor in Alzheimer's disease (AD) cognitive impairment. But the actual evidence that scientists can provide is very limited — because the subjects are very small and are commonly carried out in patients with moderate to severe diseases; in addition, the method used by the study is mostly autopsy or based on a small biopsy in a limited area of brain biopsy.
Figure 1. Intricate neural networks in the brain (Credit: Pixabay)
In response to these troubles, researchers at Yale University in the United States have developed an advanced imaging technique called positron emission tomography (PET), which allows researchers to observe the loss of synapses in the brain of a living AD patient , even if the patient's symptoms are very mild or only in the early stages of the disease.
Using PET scanning technology, on Feb. 17, Yale researchers published an online article titled "Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [11C]UCB-J" in the journal Alzheimer's & Dementia. The results of the thesis. In the study, they confirmed and successfully confirmed previous claims: the root cause of cognitive deficits in patients with AD, the destruction of synapses in the brain.
Figure 2. (Image: Alzheimer's & Dementia)
In this experiment, the researchers linked the subjects' synaptic vesicle glycoprotein 2A( SV2A) to the distribution volume ratio (DVR) of the subjects' brains to assess the consequences of synaptic changes in vivo based on the final imaging. The substance named [11C]UCB-J used in the experiment is an SVG2A PET tracer for human research that has only been developed in recent years.
*Note: SV2A is a membrane protein specifically expressed in synaptic vesicles, which is expressed in almost all synapses. It is located in the synaptic vesicles at the anterior end of the synaptic and regulates the release of action potential-dependent neurotransmitters in the brain.
After screening candidates aged 50 to 85 for eligibility, a total of 64 participants were included in the study. Of these, 45 subjects had varying degrees of AD, and 19 subjects were considered cognitively normal (CN) after measurement. All subjects underwent SV2A PET imaging scans to measure synaptic density, which allowed the scientists to visually "see" synaptic metabolic activity in the brains of 45 patients diagnosed with mild to moderate AD.
To study the relationship between synaptic density and performance in specific cognitive domains, the researchers built models that matched the performance of five cognitive domains and measured each person's cognitive performance in these five key areas: including verbal memory, language skills, executive function, and processing speed) and visuospatial ability.
As in the researchers' previous analysis, synaptic density was significantly lower in both the AD-affected brain region and the hippocampus region in the AD group. The multivariate linear regression model between synaptic density, which is an important predictor of global cognition, is significant.
Figure 3. Study of the correlation between synaptic density (DVR) and cognitive function in patients with AD (Credit: Alzheimer's & Dementia)
In further experiments, the researchers analyzed and assessed the relationship between synaptic density and overall cognition in all brain regions. The results showed that synaptic density was positively correlated with the overall cognition of the prefrontal, temporal, parietal and occipital cortex regions. These brain regions have also been observed by researchers in previous scoring for specific cognitive domains, including language skills, executive function, processing speed, and visuospatial abilities.
However, the link between synaptic density and verbal memory capacity is more limited in the cortical regions of the temporal, parietal, and occipital lobes. Interestingly, however, there was no significant correlation between synaptic density in the hippocampus and endoorhinocortex and overall cognitive or region-specific cognitive performance.
Figure 4. Correlation map between synaptic density (DVR) and overall cognition in AD patients (Credit: Alzheimer's & Dementia)
Figure 5. Correlation map between synaptic density (DVR) and region-specific cognitive performance in patients with AD (Credit: Alzheimer's & Dementia)
In summary, the loss of synapses or connections between brain cells is closely related to poor performance on cognitive tests. In addition, the researchers note that synaptic density is more predictive of a person's cognitive performance than the loss of gray matter volume in the brain, and that this correlation extends to the mild and early stages of AD.
Christopher van Dyck, director of the Yale Alzheimer's Disease Research Center and senior author of the paper, said that researchers can now track patients' gradual loss of synapses over time, which can give us a better understanding of the development of cognitive decline in individuals.
Reference:
[1] Alzheimer’s association
Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [11C]UCB-J https://doi.org/10.1002/alz.12582
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