Amyloidosis for NEET PG Pathology: Congo Red, AL vs AA vs ATTR, Kidney and Heart Involvement, Diagnosis

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🎯 Exam priority: Moderate. Expect: the Congo red finding, which protein makes AL vs AA, the inflammatory diseases that cause AA, dialysis amyloid, organs involved, and the best biopsy site.

CBME mapping: PA 9.1–9.2.

Types of amyloidosis and how amyloid is identified. Drawn by TrackNation.

What Amyloid Is

• Extracellular deposits of insoluble ~10 nm fibrils made of misfolded proteins arranged as beta-pleated sheets, with serum amyloid P component and glycosaminoglycans. Deposits are inert but crowd organs; some prefibrillar oligomers are directly toxic.

• Stains: pink on H&E; PAS and Alcian blue positive; most characteristic is apple-green birefringence under polarised light after Congo red. Electron microscopy shows non-branching 10 nm fibrils. Organs look waxy at autopsy.

Types

• AL: clonal immunoglobulin light chains from a plasma cell or B-cell clone; 10–20% of myeloma patients develop it. Targets skin, nerves, heart, gut and tongue (macroglossia), kidney, liver, spleen, vessels.

• AA: serum amyloid A, an acute-phase reactant raised by IL-1, TNF and IL-6 in chronic infection (TB, bronchiectasis, osteomyelitis, leprosy) or inflammation (rheumatoid and juvenile arthritis, Crohn disease, familial Mediterranean fever). Prefers kidneys, spleen, liver, adrenals and lymph nodes.

• Hereditary ATTRv: mutant transthyretin — the commonest hereditary type; neuropathy (carpal tunnel first), kidney and heart disease; liver transplant can remove the source. ATTRwt: normal transthyretin in the hearts of older men. Typing matters: chemotherapy is for AL, not ATTR.

• β2-microglobulin amyloid in long-term haemodialysis. Localised: amyloid beta in the brain (Alzheimer disease, amyloid angiopathy); light chains elsewhere.

Organs and Diagnosis

• Kidney: glomerular deposits → proteinuria → nephrotic syndrome or end-stage disease. Heart: restrictive (infiltrative) cardiomyopathy, diastolic failure, low ECG voltage despite a thick wall. Liver: painless, sometimes massive, hepatomegaly. Peripheral neuropathy; bruising around the eyes ("raccoon eyes") from fragile vessels.

• Diagnosis: show fibrils in tissue. Abdominal fat aspirate finds amyloid in ~80% of AL (under 25% of ATTRwt); kidney or heart biopsy is nearly 100% sensitive when involved. Then type it — mass spectrometry is the most sensitive and specific.

Traps the Examiner Sets

• Apple-green birefringence needs Congo red and polarised light.

• AL = light chains (myeloma, macroglossia); AA = serum amyloid A (TB, RA, FMF).

• Dialysis amyloid = β2-microglobulin; brain = amyloid beta.

• Thick heart wall but low ECG voltage = infiltrative (amyloid).

Memory Hooks & Shortcuts

Shortcuts to lock in this article's numbers and lists. Each one only re-packages facts proven above.

• 🧠 Congo goes Green in Polarised light — Congo red apple-green birefringence

• 🧠 AL = Light chains; AA = Acute-phase (SAA) — AL vs AA

• 🧠 Dialysis Delivers β2M — dialysis amyloid

• 🧠 Thick wall, Tiny voltage = amyloid — cardiac amyloid ECG

• 🧠 Fat first, then the organ — biopsy order

Rapid-Revision Cards

• Amyloid

  Extracellular insoluble ~10 nm fibrils, beta-pleated sheets.

• Constant components

  Serum amyloid P + glycosaminoglycans.

• Stains

  H&E pink; PAS/Alcian blue +; Congo red → apple-green under polarised light.

• EM

  Non-branching 10 nm fibrils.

• AL

  Light chains; myeloma (10–20%); macroglossia.

• AA

  Serum amyloid A; TB, bronchiectasis, RA, Crohn, FMF.

• AA targets

  Kidney, spleen, liver, adrenals, nodes.

• ATTRv

  Commonest hereditary; carpal tunnel first.

• ATTRwt

  Older men's hearts; no chemotherapy.

• Dialysis amyloid

  β2-microglobulin.

• Brain amyloid

  Amyloid beta — Alzheimer, angiopathy.

• Kidney

  Glomerular → proteinuria → nephrotic.

• Heart

  Restrictive; thick wall, low ECG voltage.

• Raccoon eyes

  Fragile amyloid vessels.

• First biopsy

  Abdominal fat (~80% AL).

• Typing

  Mass spectrometry best.

Sources

Facts in this article were checked against these documents.

• MSD Manual Professional: Amyloidosis — Merck & Co. (MSD Manuals), reviewed 2025–26 (link)

• MSD Manual Professional: Restrictive Cardiomyopathy — Merck & Co. (MSD Manuals), reviewed 2025–26 (link)

• Competency Based Undergraduate Curriculum, Pathology (PA 9) — National Medical Commission, 2024

Test Yourself: Practice Questions

Twenty-two questions in NEET PG style, most of them clinical vignettes.

Practice Questions (NEET PG pattern)

Original questions written in the style of the exam: +4 for a correct answer, −1 for a wrong one. Every answer was checked against the sources listed above. NEET PG papers are not published by NBEMS, so these are not past-paper questions.

Q1. A kidney biopsy stained with Congo red and viewed under polarised light shows apple-green birefringence. The deposit is

• (a) amyloid

• (b) fibrin

• (c) collagen

• (d) immune complexes

Q2. Amyloid fibrils are arranged as

• (a) beta-pleated sheets

• (b) random coils

• (c) alpha helices only

• (d) triple helices

Q3. Besides the fibrillar protein, all amyloid deposits contain

• (a) haemosiderin

• (b) serum amyloid P component and glycosaminoglycans

• (c) calcium phosphate

• (d) immunoglobulin heavy chains only

Q4. On routine H&E, amyloid appears

• (a) black

• (b) blue and intracellular

• (c) pink, amorphous and extracellular

• (d) unstained

Q5. Electron microscopy of an amyloid-laden heart biopsy shows

• (a) viral particles

• (b) non-branching fibrils about 10 nm wide

• (c) branching fibrils 100 nm wide

• (d) dense deposits on the basement membrane

Q6. A patient with multiple myeloma develops an enlarged tongue, heavy proteinuria and heart failure. The amyloid protein is

• (a) transthyretin

• (b) immunoglobulin light chain (AL)

• (c) serum amyloid A (AA)

• (d) β2-microglobulin

Q7. A man with long-standing untreated tuberculosis develops nephrotic syndrome. Renal biopsy shows amyloid. The precursor protein is

• (a) serum amyloid A (acute-phase reactant)

• (b) amyloid beta

• (c) light chain

• (d) transthyretin

Q8. Which condition is a recognised cause of AA amyloidosis?

• (a) familial Mediterranean fever

• (b) multiple myeloma

• (c) long-term haemodialysis

• (d) Alzheimer disease

Q9. In AA amyloidosis, serum amyloid A rises because

• (a) plasma cells make it

• (b) the kidney fails to clear it

• (c) inflammatory cytokines (IL-1, TNF, IL-6) increase its hepatic synthesis

• (d) it is inherited

Q10. AA amyloidosis typically targets the

• (a) brain only

• (b) skin only

• (c) kidneys, spleen, liver, adrenals and lymph nodes

• (d) tongue only

Q11. A patient on haemodialysis for many years develops amyloid deposits. The protein is

• (a) light chain

• (b) serum amyloid A

• (c) transthyretin

• (d) β2-microglobulin

Q12. The commonest type of hereditary amyloidosis is caused by mutant

• (a) transthyretin (ATTRv)

• (b) immunoglobulin

• (c) amyloid beta

• (d) serum amyloid A

Q13. In hereditary transthyretin amyloidosis, the neurological feature that commonly comes first is

• (a) seizures

• (b) carpal tunnel syndrome

• (c) dementia

• (d) optic neuritis

Q14. An elderly man has heart failure with a thick-walled heart; amyloid is made of normal (wild-type) transthyretin. Why must it be typed carefully?

• (a) chemotherapy is for AL amyloidosis and would be wrong for ATTRwt

• (b) it is always fatal

• (c) it is infectious

• (d) it needs dialysis

Q15. Amyloid deposits in the brain in Alzheimer disease are made of

• (a) light chains

• (b) serum amyloid A

• (c) transthyretin

• (d) amyloid beta protein

Q16. In renal amyloidosis, deposits typically start in the

• (a) ureter

• (b) renal artery only

• (c) glomerular membrane, causing proteinuria and nephrotic syndrome

• (d) renal pelvis

Q17. Cardiac amyloidosis causes which type of cardiomyopathy?

• (a) dilated

• (b) arrhythmogenic right ventricular

• (c) restrictive (infiltrative), with diastolic dysfunction

• (d) hypertrophic obstructive

Q18. Echocardiography shows a thick ventricular wall, but the ECG shows low voltage. This combination suggests

• (a) amyloid infiltration

• (b) pericardial effusion only

• (c) athlete's heart

• (d) hypertensive hypertrophy only

Q19. A patient with AL amyloidosis bruises around the eyes after coughing. The cause is

• (a) trauma only

• (b) low platelets

• (c) amyloid weakening small blood vessels

• (d) vitamin K deficiency

Q20. The simplest first biopsy to look for systemic AL amyloidosis is

• (a) bone marrow only

• (b) skin of the scalp

• (c) aspiration of subcutaneous abdominal fat (~80% positive in AL)

• (d) brain biopsy

Q21. The most sensitive and specific way to identify which protein forms the amyloid is

• (a) mass spectrometry

• (b) H&E staining

• (c) serum protein electrophoresis

• (d) Congo red alone

Q22. At autopsy, organs heavily infiltrated by amyloid look

• (a) haemorrhagic

• (b) black

• (c) cystic

• (d) waxy

Active Recall

From memory: describe what amyloid is and how it stains; name the protein and causes of AL, AA, ATTRv, ATTRwt, dialysis and brain amyloid; list the organs involved and their signs; and outline how amyloidosis is diagnosed and typed.