Amyloid

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Crossbeta

Small bowel duodenum with amyloid deposition 20X

2rnm

Protofilament of Beta Amyloid

Three phases of amyloid fibril formation.

Amyloid refers to the protein substances that are deposited in various tissues and organs of the body in a number of diseases. These proteins are misfolded and form fibrils that are insoluble and can disrupt the normal function of tissues, leading to disease. The process of amyloid deposition is known as amyloidosis, which can be systemic or localized, affecting multiple systems or a single organ, respectively.

Characteristics

Amyloid fibrils are characterized by their beta-sheet structure, which is resistant to proteolysis and leads to their accumulation in the extracellular space of tissues. This structure is identified by specific staining techniques, such as Congo red staining, which under polarized light shows a characteristic apple-green birefringence. Electron microscopy can also be used to identify the fibrillar nature of amyloid deposits.

Classification

Amyloidosis can be classified based on the type of protein that makes up the amyloid fibrils. The most common forms include:

• AL Amyloidosis (Primary Amyloidosis): Caused by the deposition of light chains produced by plasma cells. It is often associated with plasma cell dyscrasias, such as multiple myeloma.
• AA Amyloidosis (Secondary Amyloidosis): Associated with chronic inflammatory conditions, such as rheumatoid arthritis, inflammatory bowel disease, and chronic infections. The amyloid fibrils are composed of serum amyloid A protein.
• ATTR Amyloidosis: Caused by the deposition of transthyretin, which can be hereditary or acquired. It often affects the heart and the peripheral nervous system.
• Aβ Amyloidosis: Associated with Alzheimer's disease, where amyloid beta peptides accumulate in the brain.

Pathogenesis

The exact mechanism of amyloid fibril formation and deposition is not fully understood, but it involves a change in the protein's secondary structure to a beta-sheet configuration, leading to aggregation and fibril formation. Genetic factors, chronic inflammation, and certain environmental factors may contribute to the development of amyloidosis.

Clinical Manifestations

The symptoms of amyloidosis depend on the organs affected. Common manifestations include:

• Kidney involvement leading to nephrotic syndrome and renal failure.
• Heart involvement causing restrictive cardiomyopathy, arrhythmias, and heart failure.
• Nervous system involvement resulting in peripheral neuropathy.
• Gastrointestinal tract involvement, which can cause macroglossia, malabsorption, and gastrointestinal bleeding.

Diagnosis

Diagnosis of amyloidosis involves a combination of clinical evaluation, laboratory tests, imaging studies, and histological examination of tissue biopsies. The presence of amyloid fibrils can be confirmed by Congo red staining of biopsy specimens.

Treatment

Treatment of amyloidosis aims to reduce the production of the amyloid precursor protein and to manage the symptoms and organ dysfunction caused by amyloid deposits. This may involve chemotherapy, targeted therapies, and supportive care. In some cases, organ transplantation may be considered.

Prognosis

The prognosis of amyloidosis varies depending on the type of amyloidosis, the organs involved, and the extent of organ dysfunction. Early diagnosis and treatment can improve outcomes, but the disease can be life-threatening, especially if critical organs like the heart or kidneys are involved.

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