Automated multiscale high-content imaging connects plaque population heterogeneity to localized synapse loss

Automated multiscale high-content imaging in CRND8 Mus musculus links plaque-associated synapse loss to plaque type, showing primary loss from large cored plaques.

• Why it matters: Synapse loss tracks cognitive decline, but conventional confocal imaging limits throughput and sampling, making it hard to measure how localized amyloid pathology relates to synapse loss at scale.
• What they did: The authors built an automated Preciscan-based multiscale workflow on the Opera Phenix to map amyloid beta plaques tissue-wide, then acquire targeted high-magnification images and perform subcellular analysis. They analyzed hundreds of plaque images across disease progression in the CRND8 model.
• The result: Small diffuse plaques accumulate rapidly at late stages, yet synapse loss is primarily associated with large cored plaques, enabling systematic study of subcellular changes across pathological microenvironments in disease models.

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