Amyloidfibriller

Amyloidfibriller are insoluble protein aggregates characterized by a cross-beta sheet structure that stacks into long, unbranching filaments. They form when normally soluble proteins misfold and adopt a beta-sheet-rich conformation, which then aggregates through nucleation-elongation processes and can seed further fibril growth. Amyloid fibrils are typically extracellular, can deposit in various tissues, and are associated with a range of diseases known as amyloidoses.

Different precursor proteins give rise to amyloid fibrils, including immunoglobulin light chains in AL amyloidosis, serum amyloid A in AA amyloidosis, and transthyretin in ATTR amyloidosis. In the nervous system, beta-amyloid peptides derived from amyloid precursor protein accumulate to form plaques; prion proteins can also form amyloid fibrils in prion diseases.

Pathology and clinical impact: deposition disrupts tissue architecture and organ function; in the brain, amyloid plaques and amyloid deposition in blood vessels contribute to neurodegeneration and intracranial hemorrhage; systemic deposition can cause cardiomyopathy, nephrotic syndrome and neuropathies.

Diagnosis and research: detection by Congo red staining with apple-green birefringence under polarized light; electron microscopy reveals straight, non-branching fibrils; immunohistochemistry or mass spectrometry can identify fibril protein.

Treatment: many forms remain without curative therapies; management includes treating the underlying proteinopathy and supportive care; some conditions have disease-modifying options such as transthyretin stabilizers (e.g., tafamidis) or RNA interference therapies, and research into anti-amyloid antibodies is ongoing.