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

Published on July 17, 2023

Imagine trying to untangle a massive, intricate knot. You know that the knot consists of multiple strands woven together, but understanding how they all fit together is a daunting task. That’s similar to the challenge scientists face with Alzheimer’s disease (AD) and its associated pathologies. AD is like the knot, with its hallmark features of β-amyloid plaque deposition, neurofibrillary tangles, and cognitive impairment. And just like how different strands in a knot can be entangled, AD-related pathologies, such as cerebral amyloid angiopathy (CAA), share molecular drivers with AD. Thankfully, researchers are making progress in unraveling this neurological puzzle. By using spatial omics techniques, they can identify the relationships between specific cell types, tissue features, and molecular distributions in AD and its associated pathologies. These advanced technologies provide a comprehensive view of the tissue microenvironment surrounding these neuropathologies, much like a map showing how each strand in the knot is connected. As spatial omics methods continue to improve, scientists can gain a deeper understanding of the molecular causes of AD, opening doors to new possibilities for early detection, diagnosis, and treatment of this devastating disease.

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.

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