Pathogenesis and Pathology of Amyloidosis

Definition and Classification of Amyloidosis

Amyloidosis refers to a group of diseases characterized by the deposition of abnormal protein fibrils (amyloid) in various tissues and organs, leading to dysfunction. These deposits result from misfolded proteins that aggregate into insoluble fibrils.

Classification of Amyloidosis

• Primary Amyloidosis (AL): Associated with plasma cell dyscrasias, commonly seen in multiple myeloma.
• Secondary Amyloidosis (AA): Occurs due to chronic inflammatory conditions like rheumatoid arthritis or tuberculosis.
• Hereditary Amyloidosis: Includes familial amyloid polyneuropathy (FAP) caused by mutations in transthyretin (TTR) gene.
• Localized Amyloidosis: Confined to specific organs such as the brain (e.g., Alzheimer’s disease) or endocrine organs.

Pathogenesis of Amyloidosis

Amyloidogenesis occurs through protein misfolding and aggregation into β-sheet structures, leading to impaired organ function. The main mechanisms include:

• Genetic mutations causing protein misfolding.
• Chronic inflammation leading to excessive acute-phase reactants.
• Failure of proteolytic degradation mechanisms.

Pathology of Amyloid Deposits

Histologically, amyloid deposits exhibit birefringence under polarized light after Congo red staining. Electron microscopy reveals non-branching fibrils arranged in a parallel fashion.

Clinical Manifestations

Symptoms vary depending on organ involvement:

• Renal Amyloidosis: Presents as nephrotic syndrome with proteinuria.
• Cardiac Amyloidosis: Causes restrictive cardiomyopathy, leading to heart failure.
• Neurologic Amyloidosis: Results in peripheral neuropathy and autonomic dysfunction.

Conclusion

Amyloidosis is a complex disorder with diverse etiologies. Early diagnosis and targeted treatment are critical in managing disease progression.