Senile (or amyloid) plaques: characteristics and effects on the brain

Senile plaques are produced in the gray matter of the brain by the accumulation of beta-amyloid protein, which according to Researchers are listed as one of the candidate proteins when it comes to explaining the origin and maintenance of diseases such as Alzheimer's.

In this article we will see what senile plaques are and how they originate, what is its relationship with Alzheimer's disease and what treatments have been put in place to combat its presence.

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What are senile plaques?

Senile plaques, also known as neuritic plaques or amyloid plaques, are formed in the gray matter of the brain from the accumulation of extracellular deposits of degenerate and dystrophic neurites, reactive microglia and astrocytes, and a protein called beta-amyloid.

This protein is produced by a cut in the amino acid sequence of the amyloid precursor protein (APP) and performs specific functions in oxidative stress processes, cholesterol transport or antimicrobial activity, among other

For its part, ASF is a protein that is synthesized in the interneuronal spaces, in the smooth muscle cells of the wall vascular and platelets. It has been suggested that this protein acts as a receptor that binds to other chemical signal transducer proteins, being responsible, together with aggregated cells and other altered nerve fibers, for the formation of senile plaques.

Once formed, senile plaques are distributed by many regions of the brain, such as the cerebral cortex, basal ganglia, thalamus, or cerebellum. Up to three types of senile plaques can be distinguished: diffuse plaques, amyloid plaques, and compact or neuritic plaques.

Diffuse plaques are made up of non-fibrillar amyloid deposits that do not alter the neuropil (a set of neuronal processes, axons, and dendrites, and glial extensions that surround them), nor do they provoke a response from the glia, so their presence does not usually lead to cognitive impairment in the person carrier.

Amyloid plaques contain a more or less dense center; and the compact or neuritic plaques are those that have a toxic nature and are specific to neurodegenerative diseases such as Alzheimer's, because they contain senile plaques, astrocytes and activated microglia).

Amyloid plaques and Alzheimer's disease

Alzheimer's disease characterized by the accumulation of neurofibrillary tangles (abnormal protein conglomerates) and beta-amyloid protein deposits, responsible for the formation of senile plaques, as we mentioned at the beginning.

These abnormalities cause neuronal death in very important brain structures, such as the hippocampus and the cortex, involved in learning and memory processes. This neuronal death is preceded by a progressive loss of synapses and an alteration in the neuronal plasticity of the patient, which precipitates the appearance of the cognitive symptoms typical of this disease.

It is postulated to be the imbalance between the formation and elimination of beta-amyloid, and its subsequent accumulation, which triggers negative events (such as synaptic dysfunction, glial inflammation or hyperphosphorylation) that lead to said neuronal death.

Senile plaques can also be present in the brains of healthy people who do not have any symptoms, especially in old age. And the reason why some people are more resistant than others to the accumulation of these plaques is still unknown. What has been conclusively proven is that amyloid plaques are found in all people with Alzheimer's disease.

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The "amyloid cascade"

The "amyloid coat" hypothesis is one of the most prominent and influential models used to explain the origin and evolution of the most common dementia in the world, such as Alzheimer's.

This hypothesis is based on the idea that it is a chemical cascade that ends up causing the accumulation of senile plaques in the brain and subsequent neuronal destruction and loss of cognitive faculties. This accumulation would mark the pathological onset of the dementia in question.

The damage caused would be due, according to this hypothesis, to an excessive formation of beta-amyloid protein or, in any case, to a deficit in its elimination, a process that causes the degeneration and atrophy of some brain structures of the patient.

Still, the answers to the question of what triggers this chemical cascade remain controversial.. Most of the research that has been carried out in this regard has tried to find drugs capable of slowing down or slow the progression of dementia based on the idea that the goal is to interrupt the accumulation of these proteins harmful.

However, to this day there is still no consensus on what the triggers are. It is suggested that they could be rare genetic failures that would cause abnormalities in the DNA that encodes the amyloid precursor protein, which is responsible for synthesizing beta-amyloid. And this genetic error would lead to the formation of abnormal deposits that would generate senile plaques.

Another theory would suggest that the problem would not be with the precursor protein, but rather with another protein which is responsible for eliminating it. In any case, both theories suggest that the main marker for the pathological onset of dementia and Alzheimer's disease would be related to the amyloid cascade.

Antibodies to fight senile plaques

In recent years, the use of immunotherapy, a treatment aimed at stimulating the body's natural defenses, has been investigated to help in the treatment of Alzheimer's patients. It is studied how antibodies could penetrate neurons and reduce the beta-amyloid proteins that form senile plaques.

Researchers have used mice to expose them to immunoantibodies so that mice can be examined. changes produced in cells using the microscope, immunofluorescence, and other techniques advanced. His discovery lies in the fact that the antibodies bind to the beta-amyloid protein, in a specific area of ​​the protein's precursor, which is located outside the cell.

This complex of antibodies would penetrate the cell, reducing beta-amyloid levels and building plaque blocks that lie outside and between cells. The antibody would reduce the intracellular accumulation of the protein to almost a third.

In addition, evidence has been found that antibodies could inhibit the activity of two enzymes (beta-secretases) that facilitate the production of amyloid protein. It is believed that the antibodies could increase the degradation of beta-amyloid rather than inhibit its production, although it is not yet clear.

The scientific finding that antibodies could act both inside and outside cells leads to significant implications for investigating other neurodegenerative diseases and disorders autoimmune.

Bibliographic references:

• Gra, M.S., PN Padrón, RJJ Llibre. (2002). Amyloid β peptide, Tau protein and Alzheimer's disease. Rev Cubana Invest Biomed 21, 253-261.
• Hardy, J., Selkoe DJ. (2002) The amyloid hypothesis of Alzheimer's www.neurologia.com Rev Neurol 2010; 51 (8): 471-480 479 Early diagnosis of Alzheimer's disease: prodromal and preclinical phase disease: progress and problems on the road to therapeutics. Science; 297: 353-6.
• Simón, A.M., Frechilla D., Del Río J. (2010). Perspectives on the amyloid cascade hypothesis in Alzheimer's disease. Rev Neurol; 50: 667-75