Amyloidosis Primer

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What is Amyloidosis?

Amyloidosis is a group of disorders characterized by the extracellular deposition of fibrillar proteins, leading to tissue atrophy and functional compromise. The core pathogenesis centers on abnormal protein folding and aggregation, often involving immune components. It is a spectrum of diseases unified by the commonality of similar protein deposits.

Properties

Physical

Fibrils: Non-branching, indefinite length, 7.5-10.0 nm diameter.
Structure: Cross beta-pleated sheet conformation.

Chemical

Composition: 95% fibril proteins, 5% glycoprotein (P component or SAP).
Variants: 15 chemically distinct types, including AL, AA, TTR, beta2-microglobulin, beta-amyloid protein.

Classification

Systemic: Involves multiple organ systems.
Localized: Limited to a single organ.

Pathogenesis

Protein Instability: Abnormally folded proteins tend to aggregate.
Proteolytic Cleavage: Another pathway to abnormal protein structures.

Tissue Damage

Pressure Atrophy: Large protein deposits lead to loss of normal tissue.
Nutrient Exchange: May be influenced or blocked.
Toxicity: Speculative, includes oxidative stress, ion channel abnormalities, and membrane destruction.

Pathologic Features

Kidney: Mainly glomerular deposits.
Heart: Subendocardial and myocardial deposits.
Liver: Space of Disse and vasculature.
Other: Tongue nodules, peripheral nerve deposits.

Prognosis and Treatment

Prognosis: Generally poor, especially in AL-associated disease with multiple myeloma.
Treatment: Early diagnosis crucial; underlying disorder treatment can improve target organ conditions.
- Chemotherapy and/or Bone Marrow Transplantation: For clonal plasma cell disorders.
- Anti-inflammatory Drugs: For inflammatory disorders.
- Liver Transplantation: For certain types with liver-produced mutant proteins.

New Therapies

Protein Correction: Aiming to stabilize unstable proteins.
Protease Identification: Determining key proteases in pathogenesis.
Immunotherapy: A novel approach.