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Alzheimer's Secret Weapon: What Are Amyloid Plaques?
Amyloid plaques, also known as neuritic plaques or senile plaques, are extracellular deposits composed of amyloid-β (Aβ) protein that are primarily found in the gray matter of the brain. These plaques are often associated with degenerative neuronal elements, as well as large numbers of microglia and astrocytes. These plaques appear in the brain as we age, but large numbers of plaques and neurofibrillary tangles are characteristic of Alzheimer's disease.
Amyloid plaques vary in shape and size, usually showing a log-normal distribution curve in tissue sections, with an average area of approximately 400-450 square microns.
The formation of amyloid plaques is mainly caused by the misfolding and aggregation of Aβ proteins. The length and chemical modification of these aggregates affect their aggregation tendency and toxicity. Therefore, if we want to understand the impact of amyloid plaques, we must first talk about the generation of Aβ.
Amyloid β production
Amyloid β (Aβ) is a small protein, most commonly 40 or 42 amino acids in length. Aβ is released from a long parent protein called Aβ precursor protein (APP). APP is produced in many cells but is particularly abundant in neurons. The Aβ portion of this single-pass transmembrane protein is found partly on the inside and partly on the outside of the cell membrane.
To release Aβ, APP is cleaved step by step by two enzymes: first on the outside of the membrane by β-secretase (or β-amyloid cleaving enzyme (BACE)) and then on the inside by gamma-secretase. Second cut. These cleavages result in the release of Aβ protein fragments to the outside of the cell.
Identification and composition of amyloid plaques
Amyloid plaques can be observed under an optical microscope using a variety of staining techniques, including silver stain, Congo red, thiazole stain, etc. These methods each have varying degrees of sensitivity and are able to specifically label antigens in plaques.
Amyloid plaque Aβ deposits vary in size and appearance, from small filamentous accumulations of a few micrometers in diameter to larger and more dense masses forming the classic Aβ-amyloid core surrounded by sparse Aβ.
Pathology and distribution of amyloid plaques
According to research by Dietmar Thal and colleagues, amyloid plaque formation in Alzheimer's patients can be divided into five stages. Initially, the plaques appear in the neocortex and then gradually spread to other brain areas, including the hippocampus and amygdala.
In the final stages of Alzheimer's disease, plaques spread almost throughout the brain. During this process, Aβ aggregation and misfolding are accompanied by inflammatory responses in the brain, which in turn affects neurological function.
Association of Amyloid Plaques with Disease
In the neuropathological diagnosis of Alzheimer's disease, abundant Aβ plaques and neurofibrillary tangles formed by aggregation-specific Tau protein are necessary pathological features. While the number of neurofibrillary tangles generally correlates with the degree of dementia, Aβ clearly plays a central role in the risk, onset, and progression of Alzheimer's disease.
Detection of Aβ plaques usually requires microscopic analysis at autopsy, but with the use of radiolabeled reagents, these plaques can now also be observed in living patients.
Directions of Alzheimer's disease research
As research deepens, scientists are exploring the impact of various biological factors on the formation of amyloid plaques. These include possible links to environmental factors, genetic risk and chronic inflammation. Many recent studies have found that the formation of amyloid plaques may also be related to damage to brain microvessels.
In addition, studies of non-human biology have provided important insights: human ancestors and current non-human primates naturally develop amyloid plaques in their brains, but their accompanying neurofibrillary tangles Is relatively less.
With a deeper understanding of the mechanisms of these plaques, it is hoped that potential treatments for Alzheimer's disease can be developed in the future to slow or reverse the progression of the disease.
Amyloid plaques are undoubtedly a key link in the fight against Alzheimer's disease, but are their true role and impact really all we know about this disease?
