AI-Assisted Spatial Proteomics Of Immune Cells In Alzheimer's Brain

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Alzheimer’s disease (AD), a leading cause of age-related dementia, is marked by progressive memory loss, β-amyloid plaques, and tau protein tangles. This study investigates the neuroimmune axis of AD using AI-driven multiplexed imaging to analyze immune cell interactions with these pathological hallmarks. Researchers used Cell DIVE multiplexed imaging combined with IF/IHC-validated antibodies to examine spatial co-localization of resident and infiltrating immune cells in human AD brain tissue.

Key findings include the identification of immune cell subtypes such as microglia and astrocytes marked by TMEM119, IBA1, GFAP, and S100B. These cells exhibited heterogeneous expression patterns, with immune markers like HLA-DRA, CD11b, CD68, and CD4 associated with neuroinflammatory responses. Notably, immune cells near β-amyloid plaques expressed distinct marker combinations, suggesting localized neuroinflammation and unique spatial signatures potentially indicative of AD-associated neurodegeneration.

Advanced AI-guided spatial analysis revealed distinct immune activation patterns relative to plaque proximity. Cells near plaques and peripheral regions displayed unique phenotypes compared to those in the tissue interior, underscoring the heterogeneity of neuroimmune interactions. This spatial landscape offers critical insights into AD pathogenesis, identifying potential biomarkers and therapeutic targets.

These findings highlight the promise of multiplexed spatial proteomics for unraveling AD’s complexities. The study underscores the importance of integrating neuroimmune profiling into multidisciplinary research for developing effective therapies and preventive strategies tailored to the immune-genetic status of AD patients.