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Alpha-Synuclein Tied to Rapid Alzheimer’s Progression in Women, JAMA Study Finds

Using CSF seed amplification plus tau PET in 415 ADNI participants, researchers linked alpha-synuclein positivity to markedly faster tau buildup in women.

Overview

  • Alzheimer’s-related changes advanced up to 20 times faster in women with abnormal alpha-synuclein, a pattern not seen in men.
  • About 17% of participants tested positive for alpha-synuclein using a cerebrospinal fluid seed amplification assay.
  • Women who were alpha-synuclein positive showed the fastest tau accumulation at 0.066 SUVr per year with strong statistical significance.
  • The authors estimate that an 18-month tau-targeting trial would need roughly 129 alpha-synuclein–positive women versus about 518 alpha-synuclein–negative women to detect a 25% effect.
  • The team plans follow-up studies to test whether this sex-specific interaction appears in dementia with Lewy bodies and other neurodegenerative cohorts.