Dataset Information

Integrated Proteomic and Phosphoproteomic Profiling Reveals Distinct Disease- and Age-Related Molecular Alterations in the Retina and Hippocampus of APP/PS1/MAPT Mice

ABSTRACT: Background: Retinal abnormalities have emerged as promising noninvasive indicators of early Alzheimer’s disease (AD), yet the molecular relationship between retinal and hippocampal alterations remains insufficiently understood. Methods: The synchronized proteomic and phosphoproteomic profiling of the hippocampus and retina was performed in APP/PS1/MAPT transgenic mice. Differentially expressed proteins (DEPs), differentially phosphorylated peptides (DPPs), enriched pathways, and kinase perturbations were systematically analyzed to distinguish disease-related and age-related molecular patterns. Results: The retina displayed earlier and broader AD-related molecular alterations than the hippocampus. Retinal AD-related DEPs, DPPs and kinase perturbations were enriched in metabolic and molecular pathways, whereas hippocampal AD-related molecules were associated with synapse/axon/neuroactive ligand-related pathways. Two tissues shared a restricted set of dysregulated molecules, including RTN4, HDAC6 and PALS1_S84, Conclusion: This study establishes a synchronized dual-tissue, dual-omics framework for dissecting AD-related pathology and age-associated remodeling, providing new insight into eye-brain molecular crosstalk and offering a theoretical basis for retina-based, noninvasive early diagnosis of AD.

ORGANISM(S): Mus Musculus

SUBMITTER: Zheng Zhao

PROVIDER: PXD079850 | iProX | Wed Jun 17 00:00:00 GMT+01:00 2026

REPOSITORIES: iProX

ACCESS DATA

Similar Datasets

Project description:Exercise has emerged as a powerful variable that can improve cognitive function and delay age-associated cognitive decline and Alzheimer’s disease (AD), however, the underlying mechanisms are poorly understood. To determine if protective mechanisms may occur at the transcriptional level, we used microarrays to investigate the relationship between physical activity levels and gene expression patterns in the cognitively-intact aged human hippocampus. In parallel, hippocampal gene expression patterns associated with Aging and AD were assessed using publicly available microarray data profiling hippocampus from young (20-59 yrs), cognitively-intact aging (73-95 yrs) and age-matched AD cases. To identify “anti-Aging/AD” transcription patterns associated with physical activity, probesets significantly associated with both physical activity and Aging/AD were identified and their directions of expression change in each condition were compared. Remarkably, of the 2138 probesets significant in both datasets, nearly 95% showed opposite transcription patterns with physical activity compared to Aging/AD. The majority (>70%) of these anti-Aging/AD genes showed increased expression with physical activity and decreased expression in Aging/AD. Enrichment analysis of the anti-Aging/AD genes showing increased expression in association with physical activity revealed strong overrepresentation of mitochondrial energy production and synaptic function, along with axonal function and myelin integrity. Synaptic genes were notably enriched for synaptic vesicle priming, release and recycling, glutamate and GABA signaling and synaptic spine plasticity. Anti-Aging/AD genes showing decreased expression in association with physical activity were enriched for transcription-related function. These data suggest that physical activity preserves a more youthful profile in the hippocampus across multiple biological processes, providing a potential molecular foundation for how physical activity can delay age- and AD-related decline of hippocampal function.

Dataset Information

Integrated Proteomic and Phosphoproteomic Profiling Reveals Distinct Disease- and Age-Related Molecular Alterations in the Retina and Hippocampus of APP/PS1/MAPT Mice

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets