How Does Alzheimer's Disease Cause Gene Expression?

How Does Alzheimer's Disease Cause Gene Expression? ...

The findings suggest that an international group of researchers led by the UAB analyzed the genes that are expressed in neurons and astrocytes based on 800 observations, and found that it is critical to analyze molecular markers, such as genetic sequences or brain proteins, to obtain more precise assays, diagnoses, and therapies.

Although Alzheimer''s disease is one of the most studied pathologies due to its high prevalence, the molecular changes that cause astrocytes, a type of brain cell, to become reactive astrocytes, manifesting a significant morphological shift in response to a stressful situation, are still unknown. It''s no longer known why neurons in diseased brains have difficulties communicating with each other or with the astrocytes themselves.

A group of international researchers who investigated post-mortembrain samples from nearly 800 individuals, analyzed gene expression from post-mortembrain samples to determine the differences between the disease''s astrocytes and neurons from brains with the disease, and the control group, according to an article published inNeurobiology of Disease.

Researchers investigated the set of RNA molecules, or cellular transcriptome, which is used to determine which of all genes is being expressed, and to what extent. "By studying the transcriptome, we can see if silenced or overexpressed genes are found, and we can understand what is happening inside neurons and astrocytes," says Elena Galea, a researcher at the National Institute of Neurociencies (INc-UAB).

The findings have shown a high genetic heterogeneity among individuals with the same clinical diagnosis, and that more than half of the control individuals have a molecular profile of Alzheimer''s disease, which is characterized by a reduced expression of synaptic genes due to neuronal damage and death.

"This may indicate that these individuals were at a very early stage of the disease (still without symptoms), and that clinical diagnosis must be combined with the use of molecular markers, such as neuronal synapse proteins, to determine the outcome of the treatment." Dr. Galea, the author of this article and researcher at the National Cancer Research Center, claims.

As the disease develops, astrocytes reduce the expression of genes that code for mitochondrial proteins, which prevents the mitochondria of these cells from functioning well. This effect might be a corgiation of the astrocytes to compensate for the damage of the amyloid protein, and might therefore impede communication between astrocytes and neurons. "We believe this adaptation by astrocytes contributes to the worsening of the disease and therefore, we believe it may be a key point in preventing its progression

The study is the most complete transcriptomic analysis of human astrocytes in Alzheimer''s disease to date and is of great benefit due to the number of samples analyzed. These findings highlight the need to develop molecular evidence to identify patients into more genetically homogeneous groups for clinical trials and to ensure an accurate diagnosis and treatment of the disease.

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