Amyloid is an abnormal protein that aggregates into unbranched fibrils. It is caused by misfolding of normal or mutant proteins. There are different types classified by the precursor protein such as AL, AA, and Aβ. Amyloidosis involves deposition of amyloid fibrils in tissues and organs which can cause organ dysfunction. Diagnosis involves staining methods like Congo red that show apple-green birefringence under polarized light. Biopsies of affected tissues may be needed to confirm amyloidosis.

2.  Amyloid= ‘starch-like’ (Amylum—Latin)
 Virchow in mid 19th century
 Amyloids: Aggregations of un-degraded, pathologic
protein fibrils because of misfolding mechanisms.
 Amyloidosis: a group of diseases.
Background:

3. Definition: Amyloid
 “ A pathologic protein deposited between
the cells in various tissues and organs of the
body in a wide variety of clinical settings”.

4.  Non-branching fibres
 Indefinite length
 Diameter of 7.5 –10 nm.
 Cross-Beta-pleated sheet conformation:
X-ray crystallography
Infra-red spectroscopy
Physical nature of Amyloid:

5.  95%--consists of fibril proteins.
 5%--other glycoproteins
 Three most important forms:
1. AL (amyloid light chain): from plasma cells,
2. AA (amyloid associated): from liver,
3. A-Beta amyloid (seen in cerebral lesions of Alzheimer's
disease)
Chemical nature:

6. SYSTEMIC:
 Multiple myeloma—AL
 Reactive systemic am—AA
 Hemodialysis associated am—Ab2 microglobulins
 Hereditary am—AA
 Familial Mediterranean fever—AA
 Familial amyloidotrophic neuropathy—AATR
 Systemic Senile am—ATTR
Classification:

7. LOCALIZED AMYLOIDOSIS:
 Alzheimer's disease –A-beta
 Medullary carcinoma –A cal
 Islet of Langerhans: AIAPP
 Isolated atrial amyloidosis—AANF
 Prion disease –PrPsc

8. Amyloid protein Precursor Syndrome or involved tissues
AL Immunoglobulin light chain Myeloma associated
AH Immunoglobulin heavy chain Myeloma associated
ATTR Transthyretin Familial
AA (Apo) Serum amyloid A Familial
Aβ2M β2 Microglobulin Familial
AApoAI Apolipoprotein AI Joints
Agel Gelsolin Aortic
ALys Lysosomes Familial
AFib Fibrinogen α chain Familial
Acys Cystatin C Familial
Aβ Aβ protein Alzheimer's
APrPsc Prion protein Spongiform encephalitis
ACal Calcitonin C-cell thyroid tumors
AIAPP Islet amyloid polypeptide Islets of Langerhans
AANF Atrial natriuretic factor Cardiac atria
APro Prolactin Aging pituitary, prolactinomas
AIns Insulin Iatrogenic
AKer Keratoepithelin Cornea

10.  Normal proteins—when produced in excess; have inherent
tendency to fold improperly and form fibrils.
 Mutant proteins—that are structurally unstable, prone for
misfolding and aggregation.
Two categories of proteins

11.  AL type
 Abnormal B cell lesion
 Commonly associated with Plasma cell Myeloma & Other
monoclonal B cell lesions
 Increased Light chain production.
 Associated with Bence Jones Protein in Urine

12.  AA type
 Secondary to Chronic Inflammatory lesion:
 Tuberculosis, Bronchiectasis, Osteomyelitis, Rheumatoid
arthritis, Inflammatory bowel disease, Ankylosing
Spondylitis, IV drug abusers.

13. Affected organ gets enlarged, firm and waxy appearance.
 Painting the cut surface with iodine imparts a yellow color,
and that is transformed to blue-violet after application of
sulphuric acid.
 Diagnosis: Congo-red dye: ordinary light gives pink/red color;
polarized light gives apple-green birefringence.
Morphology: Gross

14. 1. Congo Red—View under Polarizing Microscopy—Apple
Green birefringence: Gold standard test.
2. Thioflavin T
3. Van Giessen (Khaki color)
4. PAS (Periodic Acid Schiff )Stain.

15.  Amorphous, eosinophilic, hyaline extra-cellular
protein.
 With progressive accumulation, produces pressure
atrophy of adjacent cells.
Microscopically:

16.  Kidney: Focal to diffuse mesangial deposits, Nodular
Basement membrane deposits, Capillary loops, Interstitial
space, Wall of blood vessels
 Liver: Hepatomegaly, Waxy surface
 Heart: Dew drop like subendocardial nodules, In between
Myocardial fibres
 Tongue: Macroglossia, Gingival swellings
 Carpel tunnel syndrome.
Morphology:

17. SPLEEN:
 Splenomegaly +
 Splenic follicles, white pulp involved—SAGO spleen:
tapioca like granules on gross examination.
 Splenic sinuses, red pulp involved– LARDACEOUS spleen
(map like-large deposits).
Qn

18.  Depend on the site involved
 Can be unsuspected finding in Autopsy
 Can lead to serious organ dysfunction
 Renal disease: Nephrotic syndrome
 Cardiac: Conduction defects, Restrictive
cardiomyopathy
 Hepatosplenomegaly

19. 1. Abdominal fat
2. Tongue
3. Rectal mucosa
4. Renal biopsy
5. Bone marrow biopsy
Biopsy site: