ABSTRACT NUMBER: ESOC2026YS143 CEREBROVASCULAR REACTIVITY AS AN EARLY WARNING MARKER OF ARIA DURING ANTI-AMYLOID THERAPY IN ALZHEIMER’'S DISEASE

Abstract Background and aims Amyloid-related imaging abnormalities(ARIA)represent the main safety concern of anti-amyloid monoclonal antibody therapy and reflect treatment-induced cerebrovascular instability rather than isolated parenchymal toxicity.ARIA pathophysiology is closely linked to cerebral amyloid angiopathy, blood–brain barrier disruption, vascular inflammation, and impaired cerebrovascular adaptability, positioning stroke physicians at the center of patient selection and monitoring. Current risk stratification relies mainly on static markers such as APOE genotype and baseline MRI features, but lacks functional, repeatable measures of cerebrovascular vulnerability. Recent evidence from biologically confirmed Alzheimer’s disease demonstrates that cerebrovascular reactivity, assessed by transcranial Doppler Breath Holding Index, is markedly reduced at baseline and shows genotype-specific associations with plasma p-tau181 and vascular–metabolic burden. The aim of this project is to evaluate cerebrovascular reactivity as a stroke-oriented biomarker to stratify ARIA risk before initiation of anti-amyloid therapy and to dynamically monitor vascular stability during treatment. Methods This prospective observational project will enroll patients with early, biomarker-confirmed Alzheimer’s disease eligible for anti-amyloid therapy. Cerebrovascular reactivity will be assessed using transcranial Doppler at baseline and serially during treatment. Evaluations will integrate APOE-genotype, plasma biomarkers including p-tau181, Aβ42/40, neurofilament light chain, and GFAP within the updated ATNVS framework, vascular and metabolic profiling, and MRI markers of small vessel disease, cerebral amyloid angiopathy, and blood–brain barrier permeability. Standard MRI surveillance for ARIA will be performed. Results Baseline cross-sectional data demonstrate reduced cerebrovascular reactivity in Alzheimer’s disease and genotype-specific associations between vascular reactivity and plasma p-tau181, supporting cerebrovascular reactivity as a functional marker of cerebrovascular vulnerability. Patient enrollment and longitudinal monitoring are currently being finalized. Conflict of interest Martina Di Donna. Nothing to disclose