Senile Plaques (or Amyloid): Characteristics And Effects On The Brain
Senile plaques are produced in the gray matter of the brain due to 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 is its relationship with Alzheimer’s disease and what treatments have been implemented to combat its presence.
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 dystrophic and degenerating neurites, microglia and reactive 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 fulfills 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 wall vascular and platelets. It has been suggested that this protein acts as a receptor that couples to other proteins that transduce chemical signals, being responsible, together with aggregated cells and other altered nerve fibers, for the formation of senile plaques.
Once formed, senile plaques They are distributed throughout 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 extensions, axons and dendrites, and glial extensions that surround them), nor do they provoke a response from the glia, so their presence is not usually present. lead to cognitive impairment in the 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 for neurodegenerative diseases such as Alzheimer’s, because they contain senile plaques, astrocytes and activated microglia).
Amyloid plaques and Alzheimer’s disease
Alzheimer’s disease It 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 we mentioned at the beginning.
These abnormalities cause neuronal death in very important brain structures, such as the hippocampus and 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 typical cognitive symptoms 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 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 all people who suffer from Alzheimer’s disease have amyloid plaques.
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 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 subsequent neuronal destruction and loss of cognitive faculties. This accumulation would mark the pathological beginning 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 carried out in this regard has tried to search for drugs capable of slowing or reducing the progression of dementia based on the idea that the objective is to interrupt the accumulation of these harmful proteins.
However, to this day there is still no consensus regarding what the triggering factors are. It is suggested that they could be rare genetic faults that would cause abnormalities in the DNA that codes for 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 of the pathological onset of dementia and Alzheimer’s disease would have to do with the amyloid cascade.
In recent years, the use of immunotherapy, a treatment aimed at stimulating the body’s natural defenses, has been investigated to help treat Alzheimer’s patients. It is studied how antibodies could penetrate neurons and reduce beta-amyloid proteins that form senile plaques.
Researchers have used mice to expose them to immunoantibodies so that changes in the cells can be examined using microscopy, immunofluorescence, and other more advanced techniques. Its discovery lies in the fact that 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 levels of beta-amyloid and building blocks of plaques that lie outside and between cells. The antibody would reduce the intracellular accumulation of the protein by 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 thought that antibodies could increase the degradation of beta-amyloid rather than inhibit its production although it is still unclear.
The scientific discovery that antibodies could act both inside and outside cells has significant implications for researching other neurodegenerative diseases and autoimmune disorders.
