On 4 March, researchers from the United States of America published an article on sex-specific associations of alpha-synuclein pathology with tau accumulation in the JAMA Network Open journal. Using data from 415 participants in the Alzheimer’s Disease Neuroimaging Initiative, the researchers found that women with positive alpha-synuclein seed amplification assay results showed significantly faster tau accumulation than all other groups, while men with positive results did not differ significantly from men with negative results.
The study examined longitudinal tau positron emission tomography data collected between 2015 and 2023, with a median follow-up of 1.23 years. Participants were either cognitively unimpaired or cognitively impaired, including people with mild cognitive impairment or dementia, at baseline. Alpha-synuclein status was determined using a cerebrospinal fluid seed amplification assay and participants were grouped as either positive or negative. Tau burden was measured in the medial temporal region and analysed using linear mixed-effects models adjusted for age, baseline cognitive status, apolipoprotein E ε4 carrier status and study site.
Among the 415 participants, 220 were women and 69 were alpha-synuclein positive. The researchers identified a significant interaction between alpha-synuclein status, sex and time on tau accumulation. Women with positive results had the fastest rate of tau accumulation. The study also estimated that tau-focused clinical trials in cognitively impaired individuals with 18-month follow-up would need far fewer alpha-synuclein-positive women than alpha-synuclein-negative women to detect a treatment effect.
The article has been published open access and can be read here: https://doi.org/10.1001/jamanetworkopen.2026.0461](https://doi.org/10.1001/jamanetworkopen.2026.0461
