Amyloid

Amyloid refers to a class of insoluble protein aggregates that share a common cross-beta sheet structure. In tissues, these aggregates form extracellular fibrils that can disrupt normal architecture and function. The term amyloid is historical and does not denote a single protein; rather, it describes the deposited material that is typically Congo red positive and exhibits apple-green birefringence under polarized light.

Amyloidosis is the group of diseases caused by amyloid deposits and can be systemic or localized. Systemic forms include AL amyloidosis, due to misfolded immunoglobulin light chains produced by abnormal plasma cells; AA amyloidosis, from serum amyloid A protein during chronic inflammation; and ATTR amyloidosis, arising from transthyretin, either hereditary variants or wild-type age-related. Other precursor proteins include beta-2 microglobulin and others. Localized amyloid can occur in specific organs without systemic spread.

In the brain, amyloid-beta peptides, derived from the amyloid precursor protein, accumulate as plaques in Alzheimer’s disease and may be accompanied by cerebral amyloid angiopathy, in which amyloid deposits coat blood vessel walls. Amyloid deposition is a pathogenic hallmark in several disorders and may involve multiple organ systems in systemic forms.

Diagnosis relies on tissue examination showing amyloid with Congo red staining and apple-green birefringence. Subtyping is essential and is usually achieved by immunohistochemistry or mass spectrometry. Additional tools include imaging with amyloid-targeting PET tracers and genetic testing in hereditary forms.

Treatment is disease-specific and largely supportive for many systemic forms. For AL amyloidosis, therapies target the underlying plasma cell disorder; ATTR may be treated with pharmacologic stabilizers or liver-targeted therapies. In neurological amyloidoses, anti-amyloid therapies are under study, with some monoclonal antibodies showing modest benefits in clinical trials.