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October 29, 2025 72 mins

A shared feature of neurodegenerative disorders is accumulation of aggregated proteins within neurons: Tau in Alzheimer's disease; alpha-synuclein in Parkinson's disease; huntingtin in Huntington's disease; and TDP43 in amyotrophic lateral sclerosis.  In this episode Ai Yamamoto – an Associate Professor Neurology at Columbia University – talks about the trail of discoveries that led to the identification of a protein called ALFY that can prevent and reverse the accumulation of such pathogenic proteins. Remarkably, her team and collaborators found that some people have a variant of the gene encoding ALFY that confers resistance of those individuals to Huntington's disease.  This discovery opens many new and exciting directions for future research aimed at better understanding what goes wrong in neurodegenerative disorders and for developing interventions counteract the disease process.

LINKS

Yamamoto Laboratory web page:  https://www.aiyamamoto-lab.org/

Dr. Yamamoto's publications: https://scholar.google.com/citations?hl=en&user=HuJslgMAAAAJ&pagesize=80&view_op=list_works

Key research articles:

https://www.cell.com/action/showPdf?pii=S0896-6273%2825%2900624-5

file:///Users/markmattson/Downloads/s41583-022-00588-3.pdf

https://www.cell.com/action/showPdf?pii=S0896-6273%2819%2931045-1

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