1. Dr Vishal Saxena MBBS,MD(Path),FICMR
Amyloidosis
Dr Vishal Saxena
MBBS,MD(Path),FICMR
Win 2009

2. Amyloidosis Definition:
A group of diseases characterized by the deposition of an extracellular protein k/a amyloid which causes
Deposition of amyloid in extracellular spaces which causes a. pressure atrophy of the adjacent cells
b. organ dysfunction.
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3. Properties of amyloid
Amyloid is a fibrillar protein.
Individual subunits form Twisted β- pleated sheet
Characteristics: Amorphous eosinophilic deposits on H & E stain
Deposits stain red with Congo Red stain
Demonstrates Apple green birefringence under polarized light.
Electron microscopy:
Linear, non-branching fiber with hollow cores.
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4. Amyloidosis of the kidney
The glomerular architecture is almost totally obliterated by the massive accumulation of amyloid.
Amyloidosis of the kidney
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5. Yellow-green birefringence( polarized light)
Congo red Stain
Amyloidosis:
A:A section of the liver stained with Congo red reveals pink-red deposits of amyloid in the walls of blood vessels and along sinusoids.
B:Note the yellow-green birefringence of the deposits when observed by polarizing microscope.
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Yellow-green birefringence( polarized light)

6. Major types of amyloid proteins & causes
Amyloid light chain (AL)
Derived from light chains of Ig
kappa or lambda light chains (e.g Bence Jones protein)
Amyloid associated (AA)
Derived from serum associated amyloid
An acute phase reactant
produced by liver ( inflammation and neoplasia)
β-Amyloid (Aβ)
Derived from β amyloid precursor protein.
protein product of chromosome 21
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7. Amyloidosis: types
Systemic
Localized
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8. Systemic amyloidosis Primary amyloidosis: Type of amyloid: AL amyloid
Derived from Precursor protein : Immunoglobulin light chain (λ chain)
Associated with Multiple myeloma.
Reactive systemic amyloidosis (secondary amyloidosis):
Type of amyloid: AA amyloid
Derived from Precursor protein : SAA
Associated with Rheumatoid arthritis, SLE, TB, Osteomyelitis, Crohn disease, cancer.
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9. Systemic amyloidosis Familial Mediterranean fever: Type of amyloid: AA
Derived from Precursor protein : SAA
Autosomal recessive disease
Recurrent inflammation, fever, and neutrophil dysfunction (mutant pyrin gene).
Familial amyloidotic neuropathy : Autosomal D
Type of amyloid : ATTR (mutant form of Transthyretin)
Derived from Precursor protein: Transthyretin
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10. Systemic amyloidosis Senile systemic amyloidosis: Transthyretin
Type of amyloid: ATTR
Derived from Precursor protein: Transthyretin
Men > 70 years old ;
May cause heart failure – restrictive cardiomyopathy & arrthymias
Hemodialysis- associated amyloidosis:
Type of amyloid: Aβ2M
Derived from β2-microglobulin
May cause carpal tunnel syndrome and joint disease.
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11. Localized types of amyloid
Senile cerebral amyloidosis:
Type of amyloid Aβ
Derived from Precursor protein: βAPP
Found in Alzhiemer plaques in the brain and in cerebral vessels
The gene for βAPP is located on chromosome 21.
Isolated atrial amyloidosis
Type of amyloid AANF
Derived from Precursor protein Atrial natriuretic factor
CNS:
Alzheimer’s disease
Β amyloid protein coded by chromosome 21.
Amyloid toxic to neurons
MC COD in Down’s syndrome patients >40 years
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12. Localized types of amyloid
Endocrine type:
Type of amyloid : A cal (calcitonin)
Derived from Calcitonin : Medullary carcinoma of thyroid
Type of amyloid: AIPP (amylin)
Derived from Islet amyloid peptide
Adult onset Diabetes Mellitus (TYPE II)
Prion Disease (CJD; KURU)
Pathologic infections prion – PrPsc
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13. Amyloidosis in Multiple Myeloma
Elderly patient ; multiple osteolytic lesion; increased serum monoclonal Ig ( M spike)
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14. Amyloidosis in medullary carcinoma thyroid
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15. Senile cardiac Amyloidosis
The atrophic myocardial fibers are separated by structureless, pink-staining amyloid (arrows).
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16. Amyloidosis in Alzhiemer’s disease
Central amyloid angiopathy
Neuritic /Senile plaques
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17. Amyloidosis in Prion disease - CJD
Spongiform changes in the brain
Cerebral atrophy
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18. Distribution of disease in systemic forms
Common sites of involvement
Heart, spleen, tongue, adrenals, liver and kidney.
Renal system: Kidney most common organ involved
Renal failure is the most common cause of death (nephrotic syndrome)
Cardiovascular system: Restrictive cardiomyopathy
low voltage EKG, cardiac arrhythmias and CHF
Gastrointestinal system:
Macroglossia, malabsorption, hepatomegaly with increased alkaline phosphatase.
Musculoskeletal system: Carpal tunnel syndrome common
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19. Techniques used to diagnose amyloidosis
Biopsy of
Rectal mucosa / gingiva / omental pad of fat or the organ involved.
Immunoelectrophoresis
to detect light chains in primary amyloidosis.
Prognosis:
The prognosis of systemic amyloidosis is poor
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20. AL (Immunoglobulin light chain)
Multiple Myeloma, other plasma cell dyscrasias, B-cell lymphoma
AA (Apo serum amyloid A)
Chronic diseases (RA, Ankylosing spondylitis, SLE, TB, Crohn disease, Chronic bronchitis, bronchiectasis, Ca)
ATTR (Transthyretin)
Familial Amyloidotic polyneuropathy
Myocardial infarction
A beta 2 microgolobulin
Hemodialysis
A beta (Beta protein precursor)
Alzheimer’s disease, Down’s syndrome
AANF
Isolated atrial amyloidosis
A cal (Calcitonin)
Medullary carcinoma thyroid
AIPP (Amylin)
DM Type II
APrP amyloid-spongioform encephalopathy.
Afib-Hereditary renal amyloidosis.

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