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The Mystery of Amyloid Generation: How Is It Formed?
Amyloid plaques, often called neuritic plaques, are found primarily in the brain's gray matter. These external deposits are composed of amyloid β (Aβ) protein and are closely associated with neurological degeneration. Although these plaques may also appear during aging, their accumulation in large numbers and accompanied by neurofibrillary tangles are typical features of Alzheimer's disease.
Amyloid plaques vary in shape and size, and their distribution in tissue sections shows a log-normal distribution curve, with an average plaque area of approximately 400-450 square microns.
The process of amyloid plaque formation is caused by the misfolding of a protein called Aβ. These misfolded Aβ proteins further aggregate into oligomers and long aggregates, eventually forming plaques. The history of this process dates back to the 19th century, when scientists first described the existence of these plaques and explored their connection to neurodegenerative diseases.
The formation and history of amyloid protein
Amyloid plaques in gray matter were first described by Paul Block and Gergo Marinescu in 1892, calling them "glial sclerotic nodules." Later, in 1898, Emil Redlich reported plaques in the brains of three patients with dementia, which he called "rice sclerosis". As research progressed, Alois Alzheimer first directly linked these plaques to dementia in 1906, although at the time the focus was mainly on neurofibrillary tangles.
These amyloid proteins form from a long, shrunken protein called Aβ precursor protein (APP) within the cell membrane. It is produced by a variety of cells and is particularly abundant in neurons. APP is first cleaved by β-secretase (BACE) and γ-secretase, a process that releases 40 or 42 amino acid long Aβ fragments that help form amyloid plaques.
The probability of amyloid plaques appearing in the brain increases significantly with age, from about 10% at age 60 to 60% at age 80.
Plaque composition and visualization
Under a microscope, amyloid plaques vary in size. A typical "classic plaque" is composed of a dense Aβ amyloid core and relatively loose Aβ circles. In addition, plaques also include abnormally swollen neural processes from different neurons and activated glial cells. These abnormal neural processes and activated glial cells are not usually present in diffuse plaques, which may be considered as an initial stage of plaque development.
The structure and appearance of Aβ deposits are also affected by different staining techniques. Techniques like silver staining, Congo red staining, and immunohistochemical staining can help us accurately identify the presence of plaques.
The role of amyloid plaques in diseaseAmyloid plaques and neurofibrillary tangles are of great significance in the pathological diagnosis of Alzheimer's disease. Although the number of tangles correlated more strongly with the severity of dementia, Aβ appeared to play a central role in the risk, initiation and progression of the disease. Modern medical examination technology can now detect Aβ accumulation frozen in the brains of Alzheimer's patients through positron emission tomography (PET), providing the possibility of early diagnosis.
Amyloid plaques are often identified together with neurofibrillary tangles in the brains of people with Alzheimer's disease.
As these findings emerge, scientists are also studying genetic and environmental risk factors for amyloid plaque formation. Recent studies have shown that problems related to brain microvascular trauma and persistent brain inflammation may accelerate the appearance of amyloid plaques.
Prospects
As scientists delve deeper into the biological background of amyloid plaques, many questions remain unanswered. For example, what role does Aβ play in normal physiological function? How do these plaques evolve as we age? These issues not only involve the boundaries of biological knowledge, but also concern our future health and quality of life. How should we respond to these challenges?
