Untangling Alzheimer’s disease with spatial multi-omics: a brief review

Alzheimer’s disease (AD) is the most common form of neurological dementia, specified by extracellular β-amyloid plaque deposition, neurofibrillary tangles, and cognitive impairment. AD-associated pathologies like cerebral amyloid angiopathy (CAA) are also affiliated with cognitive impairment and have overlapping molecular drivers, including amyloid buildup. Discerning the complexity of these neurological disorders remains a significant challenge, and the spatiomolecular relationships between pathogenic features of AD and AD-associated pathologies remain poorly understood. This review highlights recent developments in spatial omics, including profiling and molecular imaging methods, and how they are applied to AD. These emerging technologies aim to characterize the relationship between how specific cell types and tissue features are organized in combination with mapping molecular distributions to provide a systems biology view of the tissue microenvironment around these neuropathologies. As spatial omics methods achieve greater resolution and improved molecular coverage, they are enabling deeper characterization of the molecular drivers of AD, leading to new possibilities for the prediction, diagnosis, and mitigation of this debilitating disease.