A reduction of CSF tau phosphorylated at threonine 217 (p-tau217) levels was observed in the treatment group compared with the placebo group, which was modulated by baseline p-tau217 levels, with those having higher p-tau217 at baseline responding better.4 After decades of research and development of biomarkers in the Alzheimer's disease field, biomarkers are now having a substantial impact on the development of disease-modifying therapies.5 Biomarkers were central to the approval process of aducanumab, and are being used in other phase 2 studies for patient selection and assessment of target engagement and treatment efficacy. Both plasma p-tau217 and p-tau181 had an excellent diagnostic performance in differentiating patients with Alzheimer's disease dementia from other neurodegenerative disorders.6 In a cohort from the Swedish BioFINDER study, p-tau217 showed stronger correlations with amyloid-β and tau PET than other p-tau variants, as well as higher accuracy in separating Alzheimer's disease dementia from other dementias.7 In 2021, molecular imaging biomarkers also contributed to our understanding of disease mechanisms associated with microglial activation and tau spreading. The APOE3-Jacksonville variant was found to reduce APOE aggregation and enhance lipidation, which has important implications in the design of APOE-targeted therapies.10 Finally, in the fields of Lewy body dementia, frontotemporal dementia, and vascular cognitive impairment, multisite consortia across the world were building on the findings of the Alzheimer's Disease Neuroimaging Initiative.