Gene Expression Dynamics in Alzheimer's Disease

Alzheimer’s disease is hallmarked by progressive memory loss and cognitive impairment underpinned by complex molecular alterations in gene expression. Studies of post-mortem brain tissue, peripheral blood and spatially resolved transcriptomes have revealed dynamic changes in coding and non-coding RNA profiles, metabolic and mitochondrial pathways, inflammatory signalling and synaptic function. These alterations vary across disease stages, brain regions and cell types, reflecting early disturbances in proteostasis, immune homeostasis and energy metabolism. Integrative analyses of bulk, single-cell and spatial transcriptomics are beginning to map the temporal sequence of gene regulation events, from preclinical phases through symptomatic decline, and to identify biomarkers and therapeutic targets that span the central and peripheral compartments.

Research from Nature Portfolio

Recent meta-analysis of large-scale Alzheimer’s transcriptomic datasets has defined core gene modules associated with neurodegeneration. Immune-related pathways driven by toll-like receptor signalling and NF-κB activation were found to be upregulated alongside down-regulated mitochondrial and synaptic genes. Upstream regulator analysis identified key transcription factors and signalling mediators as master controllers of inflammatory and energy-metabolism networks. Protein–protein interaction mapping further isolated discrete clusters enriched for complement components, cytoskeletal regulators and synaptic proteins, offering a systems-level perspective on the interplay between immune activation and neuronal dysfunction in Alzheimer’s pathology.

Gene Expression Dynamics in Alzheimer's Disease publication trend

The graph below shows the total number of articles in gene expression dynamics in alzheimer's disease across all publications each year (not limited to Nature Index journals).

Technical terms

Transcriptome: The complete set of RNA transcripts produced by the genome in a specific cell or tissue under defined conditions.

Gene co-expression network: A computational model linking genes with correlated expression patterns across samples, often revealing functional groups or pathways.

Long non-coding RNA (lncRNA): RNA molecules longer than 200 nucleotides that do not code for proteins but regulate gene expression at transcriptional and post-transcriptional levels.

Necroptosis: A form of regulated necrotic cell death that engages specific kinases and triggers inflammatory responses.

APOE4 allele: A variant of the apolipoprotein E gene conferring increased risk for Alzheimer’s disease through altered lipid transport and amyloid metabolism.

References

1. Profiling of long non-coding RNAs in hippocampal–entorhinal system subfields: impact of RN7SL1 on neuroimmune response modulation in Alzheimer’s disease. Journal of Neuroinflammation (2024).
2. Longitudinal APOE4- and amyloid-dependent changes in the blood transcriptome in cognitively intact older adults. Alzheimer's Research & Therapy (2023).
3. Analysis and experimental validation of necroptosis-related molecular classification, immune signature and feature genes in Alzheimer’s disease. Apoptosis (2024).
4. Integrated genomic approaches identify major pathways and upstream regulators in late onset Alzheimer’s disease. Scientific Reports (2015).