Examqo › Examqo library › Pathology › General pathology · IMLE
Amyloidosis — types, staining and diagnosis
Amyloid is a protein misfolded into β-pleated sheets and deposited between cells; the type is named by the precursor protein — light chains (AL), serum amyloid A (AA), transthyretin (ATTR) and others — and diagnosis is made by Congo red staining with green birefringence under polarised light, followed by typing.
Why it matters in the exam
The bank asks which protein accumulates in which condition. In primary amyloidosis (AL), immunoglobulin light chains from a clonal plasma cell accumulate, sometimes with multiple myeloma. In secondary amyloidosis (AA), a protein derived from serum amyloid A, an acute-phase protein, accumulates when there is chronic inflammation — rheumatoid arthritis, inflammatory bowel disease, prolonged infections — and in Israel especially in familial Mediterranean fever (FMF), in which regular colchicine prevents it. Transthyretin has a "wild-type" form that deposits in the hearts of older adults — amyloid confined to the heart in a 75-year-old man — and a hereditary form with neuropathy and cardiomyopathy.
Further localised types: β2-microglobulin in long-term dialysis (carpal tunnel, joints); Aβ in Alzheimer disease and cerebral amyloid angiopathy; IAPP in the islets of Langerhans in type 2 diabetes; and calcitonin in medullary thyroid carcinoma. The organ most often affected in systemic forms is the kidney, with nephrotic syndrome; the heart (restrictive cardiomyopathy), liver, spleen and tongue (enlarged in AL) are also affected.
For diagnosis, biopsy of abdominal fat or rectum is a simple route; biopsy of the affected organ is more sensitive. Congo red appears pink-red in ordinary light and "apple-green" under polarised light. Once amyloid is proven, the type must be determined — by immunohistochemistry or mass spectrometry — because treatment differs entirely: therapy against the plasma cells in AL, treatment of the inflammatory disease in AA and transthyretin stabilisers in ATTR.
Key points
- Amyloid: β-pleated sheets, Congo red with green birefringence.
- AL from light chains; AA from serum amyloid A in chronic inflammation.
- Wild-type ATTR in the hearts of older adults.
- The kidney is the common organ in systemic forms.
- Typing is mandatory; treatment differs by type.
Summary table
| Type | Precursor protein | Clinical setting | Note |
|---|---|---|---|
| AL | Immunoglobulin light chains | Primary, myeloma | Enlarged tongue, kidney, heart |
| AA | Serum amyloid A | Chronic inflammation, FMF | Colchicine prevents it in FMF |
| ATTR | Transthyretin | Hearts of older adults; hereditary form | Confined to the heart in the elderly |
| β2-microglobulin | β2-microglobulin | Long-term dialysis | Carpal tunnel |
| Aβ and IAPP | Aβ; islet amyloid | Alzheimer; type 2 diabetes | Localised |
In the full version for subscribers
- A simple algorithm
- Memory aid
- Exam traps
- 5 review cards
- Enough for IMLE
The full version is open to subscribers of: Diagnostic pathology, Internal medicine, Medical licensing exam (IMLE).
Subscriber? Read the full topic Plans and prices 25 free questions
Sources
- Robbins and Cotran Pathologic Basis of Disease, 10th edition (2021) — Diseases of the immune system — amyloidosis
- International Society of Amyloidosis: Amyloid nomenclature recommendations, 2022 — Fibril protein nomenclature
- Gertz MA, Dispenzieri A. Systemic amyloidosis recognition, prognosis and therapy, JAMA, 2020 — Diagnosis and typing
Sources are given for further reading; the text is written afresh and not copied from them.
Reviewed by the Examqo AI Professor · 2026-11-06. The text may contain errors; when in doubt, check the source.