The study by Lorenzo and Yankner investigates the neurotoxicity of β-amyloid (βA) and its relationship to the physical state of the peptide. They created nonamyloidogenic amorphous aggregates (Am-βA) and amyloidogenic fibrils (Fib-βA) to mimic diffuse and compact plaques found in Alzheimer's disease. In primary rat hippocampal cultures, Fib-βA was found to be neurotoxic, causing significant loss of synapses and neurons, while Am-βA was not toxic. The amyloid fibril-binding dye Congo red inhibited the neurotoxicity of Fib-βA by inhibiting fibril formation or by binding to preformed fibrils. Similarly, Congo red inhibited the toxicity of diabetes-associated amylin, another type of amyloid fibril. These findings suggest that βA neurotoxicity is mediated by fibril formation and that Congo red may have therapeutic potential for Alzheimer's disease and other amyloidoses.The study by Lorenzo and Yankner investigates the neurotoxicity of β-amyloid (βA) and its relationship to the physical state of the peptide. They created nonamyloidogenic amorphous aggregates (Am-βA) and amyloidogenic fibrils (Fib-βA) to mimic diffuse and compact plaques found in Alzheimer's disease. In primary rat hippocampal cultures, Fib-βA was found to be neurotoxic, causing significant loss of synapses and neurons, while Am-βA was not toxic. The amyloid fibril-binding dye Congo red inhibited the neurotoxicity of Fib-βA by inhibiting fibril formation or by binding to preformed fibrils. Similarly, Congo red inhibited the toxicity of diabetes-associated amylin, another type of amyloid fibril. These findings suggest that βA neurotoxicity is mediated by fibril formation and that Congo red may have therapeutic potential for Alzheimer's disease and other amyloidoses.