Diagnosis of<unk>  generally requires tissue biopsy. The biopsy is assessed for evidence of characteristic amyloid deposits. The tissue is treated with various stains. The most useful stain in the diagnosis of amyloid is Congo red, which, combined with polarized light, makes the amyloid proteins appear apple-green on microscopy.<unk> so, thioflavin T stain may be used. A number of imaging techniques such as a DPD scan or SAP scan are<unk> so in use. A sample of tissue can be biopsied or obtained directly from the affected internal organ, but the first-line site of biopsy is subcutaneous abdominal fat, known as a "fat pad biopsy", due to its ease of acquisition. An abdominal fat biopsy is not completely sensitive and may result in false negatives, which means a negative result does not exclude the diagnosis of<unk> . However, direct biopsy of the affected organ may still be unnecessary as other less invasive methods of biopsy can<unk> so be used, including rectal mucosa, salivary gland, lip, or bone marrow biopsy which can achieve a diagnosis in up to 85% of people. In the amyloid deposition of the joints, there will be a decreased signal in both T1 and T2 weighted MRI images. In amyloidoma, there will be low T1 signal with gadolinium injection and low T2 signal. The type of the amyloid protein can be determined in various ways: the detection of abnormal proteins in the bloodstream (on protein electrophoresis or light chain determination); binding of particular antibodies to the amyloid found in the tissue (immunohistochemistry); or extraction of the protein and identification of its individual amino acids. Immunohistochemistry can identify AA<unk>  the majority of the time, but can miss many cases of<unk> <unk> . Laser microdissection with mass spectrometry is the most reliable method of identifying the different forms of<unk> .<unk>  was previously considered the most common form of<unk> , and a diagnosis often begins with a search for plasma cell dyscrasia, memory B cells producing aberrant immunoglobulins or portions of immunoglobulins. Immunofixation electrophoresis of urine or serum is positive in 90% of people with<unk> <unk> . Immunofixation electrophoresis is more sensitive than regular electrophoresis but may not be available in<unk> l centers.<unk> ternatively immunohistochemical staining of a bone marrow biopsy looking for dominant plasma cells can be sought in people with a high clinical suspicion for<unk> <unk>  but negative electrophoresis. ATTR is now considered to be the most common form of<unk> , and no longer considered as a rare disease. It may be either age related in wild-type ATTR (ATTRv) or familial transthyretin-associated<unk> , is suspected in people with family history of idiopathic neuropathies or heart failure who lack evidence of plasma cell dyscrasias. ATTR can be identified using isoelectric focusing which separates mutated forms of transthyretin. Findings can be corroborated by genetic testing to look for specific known mutations in transthyretin that predispose to<unk> . AA is suspected on clinical grounds in individuals with longstanding infections or inflammatory diseases. AA can be identified by immunohistochemistry staining. Image:Small bowel duodenum with amyloid deposition congo red 10X.Small bowel duodenum with amyloid deposition Congo red 10X Image:Amyloidosis, dystrophic calcification, H&E.Amyloidosis, dystrophic calcification Image:Small bowel duodenum with amyloid deposition 20X.Small bowel duodenum with amyloid deposition 20X Image:Amyloidosis, Node, Congo Red.Amyloidosis, Node, Congo Red Image:Amyloidosis, blood vessels, H&E.Amyloidosis, blood vessels, H&E Image:Amyloidosis, lymph node, H&E.Amyloidosis, lymph node, H&E Image:Amyloidosis, lymph node, polarizer.Amyloidosis, lymph node, polarizer Image:Cardiac<unk>  very high mag he.Cardiac<unk> . H&E stain. Image:Cardiac<unk>  high mag.Micrograph showing amyloid deposition (red fluffy material) in the heart (cardiac<unk> . Congo red stain. Classification Historical classification systems were based on clinical factors. Until the early 1970s, the idea of a single amyloid substance predominated. Various descriptive classification systems were proposed based on the organ distribution of amyloid deposits and clinical findings. Most classification systems included primary (i.e., idiopathic)<unk> , in which no associated clinical condition was identified, and secondary<unk>  (i.e., secondary to chronic inflammatory conditions). Some classification systems included myeloma-associated, familial, and localized<unk> . The modern era of<unk>  classification began in the late 1960s with the development of methods to make amyloid fibrils soluble. These methods permitted scientists to study the chemical properties of amyloids. Descriptive terms such as primary<unk> , secondary<unk> , and others (e.g., senile<unk> , which are not based on cause, provide little useful information and are no longer recommended. 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. For example,<unk>  caused by transthyretin is termed "ATTR". Deposition patterns vary between people but are<unk> most<unk> ways composed of just one amyloidogenic protein. Deposition can be systemic (affecting many different organ systems) or organ-specific. Many<unk>  are inherited, due to mutations in the precursor protein. Other forms are due to different diseases causing overabundant or abnormal protein production – such as with overproduction of immunoglobulin light chains (termed<unk> <unk> , or with continuous overproduction of acute phase proteins in chronic inflammation (which can lead to AA<unk> . About 60 amyloid proteins have been identified so far. Of those, at least 36 have been associated with a human disease.<unk> l amyloid fibril proteins start with the letter "A" followed by the protein suffix (and any applicable specification). See below for a list of amyloid fibril proteins which have been found in humans: Fibril protein Precursor protein Target Organs Systemic and/or localized Acquired or hereditary<unk>  Immunoglobulin light chain<unk> l organs, usually except CNS S, L A, H AH Immunoglobulin heavy chain<unk> l organs except CNS S, L A AA (Apo) serum amyloid A<unk> l organs except CNS S A ATTR Transthyretin, wild type Transthyretin, variants Heart mainly in males, lung, ligaments, tenosynovium PNS, ANS, heart, eye, leptomeninges S S A H Aβ2M β2-microglobulin, wild type β2-microglobulin, variants Musculoskeletal system ANS S S A H AApoAI Apolipoprotein A I, variants Heart, liver, kidney, PNS, testis, larynx (C terminal variants), skin (C terminal variants) S H AApoAII Apolipoprotein A II, variants Kidney S H AApoAIV Apolipoprotein A IV, wild type Kidney medulla and systemic S A AApoCII Apolipoprotein C II, variants Kidney S H AApoCIII Apolipoprotein C III, variants Kidney S H AGel Gelsolin, variants Kidney, PNS, cornea S H<unk> ys Lysozyme, variants Kidney S H<unk> ECT2 Leukocyte chemotactic factor-2 Kidney, primarily S A AFib Fibrinogen a, variants Kidney, primarily S H ACys Cystatin C, variants CNS, PNS, skin S H ABri ABriPP, variants CNS S H ADanb ADanPP, variants CNS L H Aβ Aβ protein precursor, wild type Aβ protein precursor, variant CNS CNS L L A H AαSyn α-Synuclein CNS L A ATau Tau CNS L A APrP Prion protein, wild type Prion protein variants Prion protein variant CJD, fatal insomnia CJD, GSS syndrome, fatal insomnia PNS L L S A H H ACal (Pro)calcitonin C-cell thyroid tumours Kidney L S A A AIAPP Islet amyloid polypeptidec Islets of Langerhans, insulinomas L A AANF Atrial natriuretic factor Cardiac atria L A APro Prolactin Pituitary prolactinomas, aging pituitary L A AIns Insulin Iatrogenic, local injection L A ASPCd Lung surfactant protein Lung L A ACor Corneodesmosin Cornified epithelia, hair follicles L A AMed Lactadherin Senile aortic, media L A AKer Kerato-epithelin Cornea, hereditary L A<unk> ac Lactoferrin Cornea L A AOAAP Odontogenic ameloblast-associated protein Odontogenic tumours L A ASem1 Semenogelin 1 Vesicula seminalis L A AEnf Enfurvitide Iatrogenic L A ACatKe Cathepsin K Tumour associated L A AEFEMP1e EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) Portal veins, Aging associated L A<unk> ternative An older clinical method of classification refers to<unk>  as systemic or localised: * Systemic<unk>  affect more than one body organ or system. Examples are<unk> , AA and Aβ2m. * Localised<unk>  affect only one body organ or tissue type. Examples are Aβ, IAPP, Atrial natriuretic factor (in isolated atrial<unk> , and Calcitonin (in medullary carcinoma of the thyroid) Another classification is primary or secondary. * Primary<unk>  arise from a disease with disordered immune cell function, such as multiple myeloma or other immunocyte dyscrasias. * Secondary (reactive)<unk>  occur as a complication of some other chronic inflammatory or tissue-destroying disease. Examples are reactive systemic<unk>  and secondary cutaneous<unk> . Additionally, based on the tissues in which it is deposited, it is divided into mesenchymal (organs derived from mesoderm) or parenchymal (organs derived from ectoderm or endoderm).
Amyloidosis
Sjögren syndrome  Sjögren syndrome  1
Gamasoidosis
Melioidosis
Sarcoidosis
Amyloid cardiomyopathy
Neurosarcoidosis
Cardiac amyloidosis