Amüloid

Amüloid, or amyloid, refers to a group of misfolded protein aggregates that form insoluble fibrils with a characteristic cross–beta sheet structure. These fibrils can accumulate extracellularly in tissues and organs, where they disrupt normal architecture and function. The term covers a range of disorders known collectively as amyloidoses, which can be systemic, affecting multiple organs, or localized to a single site.

Amyloidoses are traditionally classified by the precursor protein that forms the fibrils. The major systemic types include AL amyloidosis, caused by misfolded immunoglobulin light chains produced by clonal plasma cells; AA amyloidosis, derived from serum amyloid A protein during chronic inflammatory or infectious conditions; and ATTR amyloidosis, due to abnormal transthyretin protein which can be inherited (variant) or occur with aging (wild-type). Other amyloid forms involve precursor proteins such as amyloid beta in cerebral amyloidosis associated with Alzheimer's disease and beta-2 microglobulin in dialysis-related amyloidosis. Localized amyloidosis refers to deposits confined to a single organ or tissue, such as the airways, skin, or tongue.

Pathogenesis of amyloid disease involves the misfolding of precursor proteins into a fibrillar form that resists normal degradation and accumulates as deposits. This deposition disrupts tissue structure and function, and organ involvement varies by amyloid type and burden. Diagnosis typically requires tissue biopsy demonstrating Congo red–positive, apple-green birefringent deposits, with subsequent typing by immunohistochemistry or mass spectrometry. Ancillary tests may include assessment for monoclonal protein, and organ-specific evaluations (renal, cardiac, neurologic imaging).

Treatment is type-specific and aims to reduce precursor production, stabilize the fibrils, or remove existing deposits where possible. AL amyloidosis is treated with therapies targeting plasma cells; AA amyloidosis focuses on controlling the underlying inflammatory condition; ATTR amyloidosis uses transthyretin stabilizers or gene-silencing therapies. Prognosis varies widely depending on the amyloid type, degree of organ involvement, and response to therapy.