National Academy of Sciences, Proceedings of the National Academy of Sciences, 24(118), 2021
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Significance The accumulation of homocysteine, a key metabolite, is considered a risk factor for Alzheimer’s disease. This work demonstrates the ability of homocysteine to form ordered fibrillar structures. The toxicity of these structures is demonstrated in a yeast model that accumulates homocysteine. We further show the association of this observation with Alzheimer's disease pathology, including induced aggregation of a pathological protein and the presence of homocysteine structures in the brain of model mice. We suggest the targeting of homocysteine structure formation as a direction for Alzheimer's disease therapeutics.