amyloïden

Amyloïden are insoluble protein aggregates that form long, unbranched fibrils derived from misfolded precursor proteins. They adopt a cross-beta-sheet structure and can accumulate extracellularly in tissues or, less often, intracellularly, where they disrupt normal architecture and function.

Amyloid formation, or amyloidogenesis, involves misfolding of a normal protein or production of an abnormal variant, followed by aggregation into fibrils. This process can be triggered by genetic mutations, chronic inflammation, aging, or other conditions. Amyloids are categorized by their precursor protein, with common systemic forms including AL amyloidosis (immunoglobulin light chains), AA amyloidosis (serum amyloid A in long-standing inflammation), and ATTR amyloidosis (transthyretin). Localized deposits may occur in specific organs or tissues. Additional variants include beta-2 microglobulin-related amyloidosis and hereditary forms.

Clinically, amyloid deposits can cause organ dysfunction depending on location and extent, most often affecting the heart, kidneys, liver, nerves, and gastrointestinal tract. In the brain, amyloid-beta plaques and related pathology are linked to some neurodegenerative conditions such as Alzheimer's disease. Not all amyloids are harmful; some occur as functional or structural components in certain organisms.

Diagnosis relies on tissue biopsy with staining (Congo red) showing apple-green birefringence under polarized light, followed by methods to identify the specific precursor protein (immunohistochemistry, mass spectrometry). Imaging and biomarkers support assessment of organ involvement. Treatment targets the underlying source of the amyloidogenic protein or stabilizes the native protein to prevent further aggregation. Examples include therapies for ATTR amyloidosis (tafamidis, diflunisal; RNA interference agents like patisiran, inotersen) and management of AL amyloidosis with chemotherapy or stem-cell–supported regimens. Prognosis varies by type and organ involvement, with ongoing research aimed at disease-modifying therapies.