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

Senile plaques occur in the gray matter of the brain due to the buildup of beta-amyloid protein, which researchers say is one of the candidate proteins to explain the origin and maintenance of diseases such as disease. 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.

    What are senile plaques?

    Wet squares also known as neuritic plaques or amyloid plaques, Form in the gray 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 cleavage of the amino acid sequence of the amyloid precursor protein (APP) and performs specific functions in the processes of oxidative stress, cholesterol transport or antimicrobial activity, among others.

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

    Once formed, senile plaques they are distributed in a multitude of brain regions, Such as the cerebral cortex, basal ganglia, thalamus or cerebellum. There are up to three types of senile plaques: 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), and do not cause a glial response, therefore the presence does not generally imply cognitive deficiency of the transporter.

    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 like Alzheimer’s, because they contain senile plaques, activated astrocytes and 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 proteins, 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 cognitive symptoms typical of this disease.

    It is postulated that it is the imbalance between the formation and elimination of beta-amyloids, And its subsequent accumulation, which 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 brains of healthy people who have no symptoms, especially in the elderly. And it’s still not clear why some people are more resistant than others to the buildup of these plaques. What has been reliably shown is that amyloid plaques are present in all people with Alzheimer’s disease.

      The “amyloid cascade”

      The “amyloid layer” hypothesis is one of the most important and influential models used to explain the origin and course 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 which it ends up causing the accumulation of senile plaques in the brain and the consequent neuronal destruction and loss of cognitive skills. This accumulation would mark the pathological appearance of the dementia in question.

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

      However, the answers to the question of what triggers this chemical cascade remain controversial.. Most of the research done in this regard has attempted to find drugs that can slow or reduce the progression of dementia based on the idea that the goal is to stop the build-up of these harmful proteins.

      However, to this day, there is still no consensus on the triggers. It is suggested that it could be rare genetic failures that cause abnormalities in the DNA encoding the amyloid precursor protein, which is responsible for the synthesis of 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 is not with the precursor protein, but rather with another protein. who is responsible for removing it. In all cases, the two theories suggest that the main marker of the pathological onset of dementia and Alzheimer’s disease is linked to the amyloid cascade.

      Antibodies to fight senile plaques

      In recent years, research has been conducted into the use of immunotherapy, a treatment designed to stimulate the body’s natural defenses, to help treat patients with Alzheimer’s disease. We are studying how antibodies could penetrate neurons and reduce the beta-amyloid proteins that make up senile plaques.

      The researchers used mice to expose them to immunoantibodies, so that changes in cells could be examined using the microscope, immunofluorescence and other more advanced techniques. Their discovery lies in the fact that the antibodies bind to the beta-amyloid protein, in a specific area of ​​the precursor of the protein, located outside the cell.

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

      Additionally, antibodies have been shown to inhibit the activity of two enzymes (beta-secretases) that facilitate the production of amyloid proteins. Antibodies are thought to increase the breakdown of beta-amyloid rather than inhibit its production, Although it is not yet clear.

      The scientific discovery that antibodies could act both inside and outside cells has important implications for being able to investigate other neurodegenerative and autoimmune diseases.

      Bibliographical references:

      • Gra, MS, PN Census, RJJ Book. (2002). Amyloid β peptide, Tau protein and Alzheimer’s disease. Rev Cubana Invest Biomed 21, 253-261.
      • Hardy, J., DJ Selkoe. (2002) The Alzheimer’s Amyloid Hypothesis www.neurologia.com Rev Neurol 2010; 51 (8): 471-480 479 Early diagnosis of Alzheimer’s disease: disease in the prodromal and preclinical phase: progress and problems on the path to therapy. Science; 297: 353-6.
      • Simon, AM, Frechilla D., De el Riu J. (2010). Perspectives on the amyloid cascade hypothesis in Alzheimer’s disease. Rev Neurol; 50: 667-75

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