Amyloidosis is a group of uncommon disorders characterized by the abnormal accumulation of misfolded proteins, known as amyloid, into insoluble deposits within the body’s tissues and organs. These deposits can build up in virtually any organ, including the heart, kidneys, liver, and nervous system, leading to organ dysfunction and eventual failure. Because the symptoms often mimic those of more common diseases, diagnosis is frequently delayed. Early and accurate detection is paramount, as the specific type of amyloidosis dictates the appropriate treatment strategy and impacts the patient’s outcome.
Blood Tests Used for Screening and Monitoring
Blood tests serve as the primary screening tool for amyloidosis, offering an initial indication of the disease’s presence and monitoring its physiological impact. These tests do not directly confirm amyloid deposits but rather detect the abnormal proteins that form the deposits or monitor the damage caused to affected organs. A standard part of the initial workup involves looking for abnormal proteins in the blood, particularly in suspected Immunoglobulin Light-chain (AL) amyloidosis, the most common type.
Two key methods for detecting these circulating abnormal proteins are Serum Protein Electrophoresis (SPEP) and Immunofixation Electrophoresis (IFE). The SPEP test separates blood proteins based on their electrical charge and size; it may reveal an abnormal spike, or “M-spike,” indicating an overproduction of a single type of antibody protein. IFE is a more sensitive follow-up test that specifically identifies the type of monoclonal protein. This identification is necessary because the plasma cell disorder underlying AL amyloidosis produces these single-type proteins.
Beyond detecting the precursor protein, a panel of blood tests assesses the functional status of major organs commonly targeted by amyloid deposits. Kidney involvement is often monitored by checking levels of creatinine and Blood Urea Nitrogen (BUN), with elevated levels suggesting reduced kidney filtration. Liver function can be checked through tests like Alkaline Phosphatase (ALP), where an increased level may suggest amyloid infiltration.
Cardiac involvement is monitored using specific blood markers. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a hormone released by the heart muscle cells in response to stress and strain; elevated levels can signal severe cardiac dysfunction due to amyloid deposits. Similarly, elevated levels of cardiac troponin, a protein released when heart muscle is damaged, can indicate injury to the heart tissue. These cardiac biomarkers are used to stage the disease and track a patient’s response to treatment.
Identifying the Specific Amyloid Protein Type
Once screening tests suggest the possibility of amyloidosis, further blood work is required to precisely identify the specific precursor protein. This step is necessary for selecting the correct therapy. There are over 30 different types of amyloidosis, but the most common systemic forms—AL, AA, and ATTR—are caused by different proteins. The treatment for each is distinct, making accurate typing important.
For AL amyloidosis, the Serum Free Light Chain (FLC) assay measures the concentration of unbound kappa and lambda light chains in the blood. In AL amyloidosis, plasma cells in the bone marrow produce an excess of one type of light chain, which then misfolds and forms the amyloid deposits. The test detects an abnormal ratio between the involved and uninvolved light chains, indicating the presence of a plasma cell disorder.
Identifying the transthyretin (ATTR) type of amyloidosis relies on different blood-based analyses. ATTR amyloidosis is caused by the misfolding of the transthyretin protein, which can be acquired later in life (wild-type) or inherited (hATTR). Genetic testing, performed on a blood sample, sequences the TTR gene to check for specific mutations, confirming the hereditary form of the disease.
For the AA type, which is secondary to chronic inflammatory conditions like rheumatoid arthritis, blood tests measure the level of Serum Amyloid A (SAA) protein. High, persistent SAA levels suggest that this protein is the source of the amyloid fibrils. These specific tests move beyond general screening to provide the molecular fingerprint of the disease, guiding physicians toward a targeted treatment approach.
Why Tissue Biopsy Remains the Definitive Diagnosis
Despite the sophistication and predictive power of blood tests, the tissue biopsy remains the definitive method for diagnosing amyloidosis. The fundamental limitation of blood tests is that they only detect the precursor protein circulating in the blood. They cannot confirm that this protein has actually deposited in the organs as amyloid fibrils. A confirmed diagnosis requires physical evidence of these deposits.
A biopsy involves taking a small sample of tissue, often from the abdominal fat pad, bone marrow, or an affected organ, for laboratory analysis. The tissue sample is then stained with a special dye called Congo red. When viewed under polarized light, the presence of amyloid is confirmed if the stained deposits exhibit a characteristic “apple-green” birefringence.
This visualization step differentiates amyloidosis from other diseases that may cause elevated levels of the same precursor proteins or similar organ dysfunction. Furthermore, the biopsy tissue allows for advanced techniques like mass spectrometry to be performed, which precisely identifies the chemical structure of the amyloid fibril. This provides the most reliable method for typing the amyloid, ensuring the patient receives the correct, type-specific treatment. While blood tests are instrumental in raising suspicion and monitoring treatment, the biopsy is the final, necessary step to confirm the diagnosis.