Senile plaques are produced in the grey matter of the brain by the accumulation of the beta-amyloid protein, which according to researchers is 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 their relationship with Alzheimer’s disease is and what treatments have been put in place to combat their presence.

What are senile plaques?

Senile plaques, also known as neuritic or amyloid plaques , form in the grey matter of the brain from the accumulation of extracellular deposits of dystrophic and degenerated 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 (APS) and has specific functions in oxidative stress processes, cholesterol transport or antimicrobial activity, among others.

On the other hand, AFP is a protein that is synthesized in the interneuronal spaces, in the vascular smooth muscle cells and in the platelets. It has been suggested that this protein acts as a receptor that attaches to other chemical signal transducing proteins, being responsible, along with aggregated cells and other altered nerve fibers, for the formation of senile plaques.

Once formed, senile plaques are distributed over 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-fibrillary amyloid deposits that do not alter the neuropyl (a set of neuronal extensions, axons and dendrites, and glial extensions that surround them), nor do they provoke a glia response, so their presence does not usually lead to cognitive impairment in the carrier.

Amyloid plaques contain a more or less dense centre; and compact or neuritic plaques are those that are toxic in nature and 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 is characterized by the accumulation of neurofibrillary tangles (abnormal protein clusters) and deposits of beta-amyloid protein, which is 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 cortex, which are 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 the formation and elimination of beta-amyloid , and its subsequent accumulation, that triggers the negative events (such as synaptic dysfunction, glial inflammation or hyperphosphorylation) that lead to this neuronal death.

Senile plaques can also be present in the brain of healthy people who do not have any symptoms, especially at older ages. And it is not yet known why some people are more resistant than others to the accumulation of these plaques. What has been clearly demonstrated is that amyloid plaques are present in all people with Alzheimer’s disease.

The “amyloid waterfall”

The “amyloid jacket” hypothesis is one of the most prominent and influential models used to explain the origin and evolution of the world’s most common dementia, such as Alzheimer’s disease.

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 the subsequent neuronal destruction and loss of cognitive faculties. This accumulation would mark the pathological beginning of the dementia in question.

According to this hypothesis, the damage caused is due 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 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 tried to look for 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, there is still no consensus as to what the triggers are. It is suggested that rare genetic failures may be causing abnormalities in the DNA encoding for 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 point out that the problem would not be the precursor protein, but rather another protein that takes care of 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 fight senile plaques

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

Researchers have used mice to expose them to immunoantibodies so that changes in the cells can be examined using the microscope, immunofluorescence and other more advanced techniques. Their discovery is that antibodies bind to the beta-amyloid protein in a specific area of the protein’s precursor, which is found outside the cell.

This antibody complex would penetrate the cell, reducing the levels of beta-amyloid and building blocks of plates outside and between the cells. The antibody would reduce the intracellular buildup of the protein to about one-third.

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

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

Bibliographic references:

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  • Simón, A.M., Frechilla D., Del Río J. (2010). Perspectives on the hypothesis of the amyloid cascade in Alzheimer’s disease. Rev Neurol; 50: 667-75