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

A summary of the characteristics of amyloid or senile plaques, linked to dementias.

Senile plaques are produced in the gray matter of the brain by the accumulation of the beta-amyloid protein, which researchers believe is one of the candidate proteins for explaining the origin and maintenance of diseases such as Alzheimer's disease.

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

What are senile plaques?

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

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

For its part, PPA is a protein that is synthesized in the interneuronal spaces, in the smooth Muscle cells of the vascular wall and in platelets. vascular wall and platelets. It has been suggested that this protein acts as a receptor that couples 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 in many regions of the brain, such as the cerebral cortex, basal ganglia, thalamus and cerebellum.such as the cerebral cortex, basal ganglia, thalamus or cerebellum. 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 prolongations, axons and dendrites, and glial prolongations that surround them), nor provoke a response from the glia, so their presence does not usually lead to cognitive impairment in the carrier.

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

Amyloid plaques and Alzheimer's disease

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

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 patient's neuronal plasticity, which precipitates the appearance of the cognitive symptoms typical of this disease.

It is postulated that it is the imbalance between beta-amyloid formation and elimination, and its subsequent accumulation, that precipitates the onset of the cognitive symptoms typical of this disease.and its subsequent accumulation, which triggers the negative events (such as synaptic dysfunction, glial inflammation or hyperphosphorylation) that lead to neuronal death.

Senile plaques can also be present in the brains of healthy people who have no symptoms, especially at older ages. And the reason why some people are more resistant than others to the accumulation of these plaques is still unknown. What has been reliably demonstrated is that amyloid plaques are present in all people suffering from Alzheimer's disease.

The "amyloid cascade"

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

This hypothesis is based on the idea that it is a chemical cascade that leads to the accumulation of plaques. 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 degeneration and atrophy of some of the patient's brain structures.

However, the answers to the question of what triggers this chemical cascade remain controversial.. Most of the research that has been done on this subject has sought to find drugs capable of slowing or reducing the progression of dementia based on the idea that the aim is to interrupt the accumulation of these harmful proteins.

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

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

Antibodies to combat 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. The way in which the antibodies could penetrate the neurons is being studied. and reduce the beta-amyloid proteins that form senile plaques.

The researchers have used mice to expose them to immunoantibodies, so that the changes produced in the cells can be examined using microscopy, immunofluorescence and other more advanced techniques. Their discovery is that the antibodies bind to the beta-amyloid protein in a specific area of the protein precursor, which is located on the outside of the cell.

This antibody complex would penetrate the cell, reducing beta-amyloid levels and building blocks of plaques found outside and between cells. The antibody would reduce intracellular accumulation of the protein by almost one-third.

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

The scientific finding that antibodies may act both inside and outside cells has significant implications for research into other neurodegenerative diseases and autoimmune disorders.

References:

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• 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.