The Inflammasome Adaptor Protein ASC in Plasma as a Biomarker of Early Cognitive Changes

Dementia is a group of symptoms including memory loss, language difficulties, and other types of cognitive and functional impairments that affects 57 million people worldwide, with the incidence expected to double by 2040. Therefore, there is an unmet need to develop reliable biomarkers to diagnose early brain impairments so that emerging interventions can be applied before brain degeneration. Here, we performed biomarker analyses for apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid-β 42/40 (Aβ_42/40) ratio in the plasma of older adults. Participants had blood drawn at baseline and underwent two annual clinical and cognitive evaluations. The groups tested either cognitively normal on both evaluations (N_N), cognitively normal year 1 but cognitively impaired year 2 (N_I), or cognitively impaired on both evaluations (I_I). ASC was elevated in the plasma of the N_I group compared to the N_N and I_I groups. Additionally, Aβ₄₂ was increased in the plasma in the N_I and I_I groups compared to the N_N group. Importantly, the area under the curve (AUC) for ASC in participants older than 70 years old in N_N vs. N_I groups was 0.81, indicating that ASC is a promising plasma biomarker for early detection of cognitive decline.