[5] These include fatigue, peripheral edema, weight loss, shortness of breath, palpitations, and feeling faint with standing.

[5] In wild-type ATTR amyloidosis, non-cardiac symptoms include: bilateral carpal tunnel syndrome, lumbar spinal stenosis, biceps tendon rupture, small fiber neuropathy, and autonomic dysfunction.

[6] The four most common types of systemic amyloidosis are light chain (AL), inflammation (AA), dialysis-related (Aβ2M), and hereditary and old age (ATTR and wild-type transthyretin amyloid[7]).

Amyloid deposition in the kidney often involve the glomerular capillaries and mesangial regions, affecting the organ's ability to filter and excrete waste and retain plasma protein.

EKG changes may be present, showing low voltage and conduction abnormalities like atrioventricular block or sinus node dysfunction.

[medical citation needed] On echocardiography, the heart shows a restrictive filling pattern, with normal to mildly reduced systolic function.

Autonomic neuropathy can present as orthostatic hypotension but may manifest more gradually with nonspecific gastrointestinal symptoms like constipation, nausea, or early satiety.

[15] Potential symptoms include weight loss, diarrhea, abdominal pain, heartburn (gastrointestinal reflux), and GI bleeding.

[15] Amyloidosis may also affect accessory digestive organs including the liver, and may present with jaundice, fatty stool, anorexia, fluid buildup in the abdomen, and spleen enlargement.

Adrenal infiltration may be harder to appreciate given that its symptoms of orthostatic hypotension and low blood sodium concentration may be attributed to autonomic neuropathy and heart failure.

)[citation needed] Amyloid proteins deposit most commonly inside the knee, followed by hands, wrists, elbow, hip, and ankle, causing joint pain.

Twenty percent of people with AL amyloidosis have an enlarged tongue, that can lead to obstructive sleep apnea, difficulty swallowing, and altered taste.

Alternatively immunohistochemical staining of a bone marrow biopsy looking for dominant plasma cells can be sought in people with a high clinical suspicion for AL amyloidosis but negative electrophoresis.

[citation needed] The modern era of amyloidosis classification began in the late 1960s with the development of methods to make amyloid fibrils soluble.

The modern classification of amyloid disease tends to use an abbreviation of the protein that makes the majority of deposits, prefixed with the letter A.

[medical citation needed] Other forms are due to different diseases causing overabundant or abnormal protein production – such as with overproduction of immunoglobulin light chains (termed AL amyloidosis), or with continuous overproduction of acute phase proteins in chronic inflammation (which can lead to AA amyloidosis).

See below for a list of amyloid fibril proteins which have been found in humans:[29] Transthyretin, variants PNS, ANS, heart, eye, leptomeninges

Treatment with high dose melphalan, a chemotherapy agent, followed by stem cell transplantation has shown promise in early studies and is recommended for stage I and II AL amyloidosis.

In people who have inflammation caused by AA amyloidosis, tumour necrosis factor (TNF)-alpha inhibitors such as infliximab and etanercept are used for an average duration of 20 months.

Long-term efficacy and safety of inotersen use in people with mutant TTR-related amyloidosis is still be evaluated in a phase-III clinical trial as of 2021.

Additionally, low-certainty evidence suggests that patisiran mitigates decreases in quality-of-life and slightly reduces the rate of adverse events versus placebo.

[5] In 2021, in a clinical trial using the CRISPR gene-editing technique, several participants had an "80% to 96% drop in TTR levels, on par or better than the average of 81%" who were given patisiran.

[40] Vutrisiran was approved by the U.S. Food and Drug Administration (FDA) in June 2022, for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults.

[45] Outcomes in a person with AA amyloidosis depend on the underlying disease, organ(s) affected, and correlate with the concentration of serum amyloid A protein.

[49][5] AA amyloidoses is the most common form in developing countries and can complicate longstanding infections with tuberculosis, osteomyelitis, and bronchiectasis.

[50] The most common causes of AA amyloidosis in the West are rheumatoid arthritis, inflammatory bowel disease, psoriasis, and familial Mediterranean fever.

[10] People undergoing long-term hemodialysis (14–15 years) can develop amyloidosis from accumulation of light chains of the HLA 1 complex which is normally filtered out by the kidneys.

[51] ATTR is found in 13–19% of people experiencing heart failure with preserved ejection fraction, making it a very common form of systemic amyloidosis.

[52] Treatments for ATTR-related neuropathy include TTR-specific oligonucleotides in the form of small interfering RNA (patisiran) or antisense inotersen,[53] the former having recently received FDA approval.

[55] Based on available research, liver transplant remains the most effective treatment option for advanced ATTR amyloidosis, protein stabilizing drugs may slow disease progression but were insufficient to justify delay of liver transplant, and newer agents such as patisiran require additional studies.