Alzheimers Dement. 2025 Dec;21 Suppl 5:e099006. doi: 10.1002/alz70859_099006.

ABSTRACT

BACKGROUND: Alzheimer’s Disease (AD) is influenced by an intricate interplay of genetic, metabolic, and microbial factors. Recent studies highlight the critical roles of the gut-brain axis, lipid metabolism, bile acids, and systemic inflammation in AD progression. The 3DNasal project integrates spatial intelligence, biofilm technology, and multi-omics insights to develop a scalable, precision-based therapeutic platform targeting AD’s multifactorial pathology.

METHOD: Objective: To design a biofilm-based nasal spray incorporating findings from metabolomics, microbiome research, and genomics (e.g., Dilmore et al., 2024; Mohanty et al., 2024) to restore microbiome homeostasis, reduce neuroinflammation, and enhance systemic resilience against AD progression.

RESULT: Preclinical findings demonstrate improved biofilm adhesion, enhanced delivery to the olfactory bulb, and significant modulation of the gut-brain axis. Data reveal that the Mediterranean Ketogenic Diet mitigates AD risk factors through serum and CSF metabolomics (Schweickart et al., 2024). Multi-omics analyses further identify novel microbial and metabolic signatures associated with AD pathology (Dilmore et al., 2024) and systemic inflammation (Liang et al., 2024) CONCLUSION: The 3DNasal project represents a novel therapeutic paradigm by integrating spatial intelligence, multi-omics, and bioengineering. This precision-based approach targets localized and systemic drivers of AD, paving the way for scalable and adaptive interventions. Future research will focus on clinical validation, adaptive personalization, and exploration of lifestyle-microbiome interactions to optimize therapeutic outcomes.

PMID:41447511 | DOI:10.1002/alz70859_099006

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