Molecular pathways and diagnosis in spatially resolved Alzheimer’s hippocampal atlas by Pan Wang,1,2,3,18 Lei Han,4,5,18 ISBN 101016/JNEURON202503002 instant download

Molecular pathways and diagnosis in spatially resolved Alzheimer’s hippocampal atlas by Pan Wang,1,2,3,18 Lei Han,4,5,18 ISBN 101016/JNEURON202503002 instant download

SUMMARYWe employed Stereo-seq combined with single-nucleus RNA sequencing (snRNA-seq) to investigate thegene expression and cell composition changes in human hippocampus with or without Alzheimer’s disease(AD). The transcriptomic map, with single-cell precision, unveiled AD-associated alterations with spatialspecificity, which include the following: (1) elevated synapse pruning gene expression in the fimbria of AD,with disrupted microglia-astrocyte communication likely leading to disorganized synaptic structure; (2) aglobally increased energy generation in the cornu ammonis (CA) region, with varying degrees across its subregions; (3) a significant reduction in the number of CA1 neurons in AD, while CA4 neurons remained largelyunaffected, potentially due to gene alterations in CA4 conferring resilience to AD; and (4) aggravated amyloidbeta (Ab) plaques in CA1 and stratum lucidum, radiatum, and moleculare (SLRM), and integration of Stereoseq map with Ab staining revealed a sequential enrichment of microglia and astrocytes around Ab plaques.Finally, reduced brain-derived extracellular vesicles carrying cholecystokinin (CCK) and peripheral myelinprotein 2 (PMP2) in AD plasma highlighted their diagnostic potential for clinical applications.