Amyloid deposits are abnormal clumps of protein that accumulate in various tissues and organs. These deposits are characterized by their fibrillar appearance and a specific beta-pleated sheet structure. Their buildup can interfere with normal bodily functions and is linked to various health conditions.
How Amyloid Deposits Form
The formation of amyloid deposits begins when normally soluble proteins misfold. These misfolded proteins then aggregate, forming insoluble fibers, typically 7-13 nanometers in diameter. These fibers are resistant to the body’s usual protein degradation processes.
This process involves several steps, starting with protein monomers. These monomers interact and nucleate, forming a stable core for aggregation. Pre-existing amyloid fibrils can accelerate this process by acting as a template, or “seed,” for aggregation. Over time, these aggregates mature into rigid, non-branching amyloid fibrils that deposit within and around cells.
Diseases Associated with Amyloid Deposits
Amyloid deposits are implicated in conditions known as amyloidoses, affecting various organs. Alzheimer’s disease, a neurodegenerative disorder, is characterized by amyloid-beta (Aβ) peptides accumulating in the brain, forming plaques outside nerve cells. Misfolded tau protein also forms neurofibrillary tangles inside neurons; Aβ is thought to play a role in their formation.
Systemic amyloidoses involve widespread protein deposits in organs like the heart, kidneys, liver, and spleen. Light-chain (AL) amyloidosis, the most common type, results from abnormal plasma cells producing excess, misfolded immunoglobulin light chains. These fragments accumulate in various tissues. AA amyloidosis is caused by fragments of serum amyloid A (SAA) protein and frequently affects the kidneys, often as a complication of chronic inflammatory diseases like rheumatoid arthritis.
Transthyretin (ATTR) amyloidosis involves misfolded transthyretin protein, which can be inherited (familial ATTR) or arise from normal, “wild-type” transthyretin as people age. This protein, primarily made in the liver, can deposit in various tissues, including the heart and nerves. Type 2 Diabetes is associated with islet amyloid polypeptide (IAPP) deposits in the pancreas. Dialysis-related amyloidosis (DRA) is another condition where beta-2 microglobulin forms deposits in joints and skeletal tissue in individuals on long-term hemodialysis.
How Amyloid Deposits Cause Damage
Amyloid deposits cause damage by disrupting normal tissue and cellular function. One mechanism is physical displacement and disruption of normal tissue architecture. These insoluble protein clumps can replace healthy cells and interfere with organ integrity, leading to dysfunction. For instance, in the kidneys, amyloid deposits can block filters, leading to protein leakage into the urine and swelling.
Beyond physical obstruction, amyloid fibrils can exert direct toxicity to cells. Soluble amyloid oligomers, smaller aggregates formed during fibril development, contribute to cellular stress and death. These toxic aggregates can perturb cellular membranes and interfere with cell-to-cell communication. The body’s attempt to clear these misfolded proteins can also trigger inflammatory responses, further contributing to tissue damage.
Identifying and Addressing Amyloid Deposits
Diagnosing amyloid deposits often begins with clinical suspicion based on symptoms like unexplained heart failure or kidney problems. A definitive diagnosis involves obtaining tissue samples through a biopsy, often from the abdominal fat pad, rectum, or affected organs. The gold standard for detection is Congo red staining, which shows a characteristic apple-green birefringence under polarized light if amyloid is present.
After confirming amyloid deposits, determining the specific type of amyloid protein is important for guiding treatment. Techniques like immunohistochemistry, immunoelectron microscopy, or mass spectrometry can identify the protein type. Blood and urine tests also detect abnormal protein levels and assess organ function. Imaging tests like echocardiograms for the heart or PET scans for specific amyloids help evaluate organ involvement and damage.
Addressing amyloidosis generally involves strategies aimed at reducing the production of the amyloid-forming protein, clearing existing deposits, or managing symptoms. For AL amyloidosis, treatments often include chemotherapy to target abnormal plasma cells producing faulty light chains. Targeted therapies, including medications that prevent proteins from misfolding, are also being developed. In some cases, organ transplants may be considered if organs are severely damaged or if the liver is the source of the amyloid-forming protein.