Molecular signatures and spatial distribution of disease-associated cellular populations in early-onset Alzheimer's disease mouse brain

Alzheimer's disease (AD) is a multifaceted neurodegenerative disorder. Grasping the pathological transformations in early-phase AD is important. Integrating single-cell and spatial transcriptomics with the pathophysiology of AD from the same origin permits to delineate molecular characteristics and spatial arrangement of cellular populations without individual differences, however, such experimental designs have been ignored in current studies. Here, we use a single-source experimental framework to create a multimodal dataset of disease-susceptible region in early-onset Alzheimer's Disease (EOAD) mouse. Predicated on amyloid-beta (Aβ) immunopathology, a profile of disease-associated alterations is discerned. Mature myelinating oligodendrocytes within fiber tracts exhibit compromised fatty acid synthesis and energy-related processes. Region-specific glutamatergic neurons demonstrate impaired synaptic formation, coupled with transcriptomic modifications that encompass energy homeostasis, lipid metabolism and cellular adhesion. Disease-associated astrocytes, aggregating around Aβ deposits, exhibit neuron-related changes in oxidative phosphorylation (OxPhos) and metal ion responses. This investigation serves as a resource for exploring disease signature across multimodal, which provides a basis for finding the progression mechanisms of AD.