The long road to recognition: a historical review of amyloidosis from early pathology to disease-modifying therapy

Within the last several decades, great strides are being made in both the diagnosis and treatment of cardiac amyloidosis, yet the condition itself has been a severely under-recognized cause of heart failure for centuries. For much of medical history, the accumulation of these insoluble fibril deposits was an enigmatic finding, observed primarily post-mortem in patients suffering from chronic inflammatory conditions. This review traces the fascinating evolution of amyloidosis: from its origins as a botanical term mistakenly applied to human pathology, through the serendipitous discoveries of histological stains like Congo red, to the molecular triumphs that identified the specific precursor proteins driving the AL, AA, and ATTR subtypes. By understanding the historical roadblocks and breakthroughs, we can better appreciate the modern diagnostic imaging and targeted therapies that are finally bringing this complex disease out of the shadows.