# Exploring Gene Expression Patterns in Alzheimer’s Disease Using a Human Microarray Data Meta-Analysis

**Authors:** Eleni Dermitzaki, Vasileios L. Zogopoulos, Apostolos Malatras, Vasiliki Georgopoulou, Petrina-Marina Aslanoglou, Adamantia Teta, Maria Rea Kalligianni, Christos Karoussiotis, Vassiliki A. Iconomidou, Ioannis Sotiropoulos, Ioannis Michalopoulos

PMC · DOI: 10.3390/biology15040345 · Biology · 2026-02-16

## TL;DR

This study uses a meta-analysis of microarray data to identify gene expression changes in Alzheimer’s disease, revealing immune activation and reduced synaptic activity.

## Contribution

The study provides a comprehensive meta-analysis of gene expression in Alzheimer’s disease, identifying potential biomarkers for early diagnosis and treatment.

## Key findings

- Alzheimer’s disease shows increased activity in immune-related genes and decreased activity in synaptic communication genes.
- A total of 4218 differentially expressed genes were identified, with 1944 up-regulated and 2274 down-regulated.
- The findings suggest immune response and inflammation are prevalent in Alzheimer’s, while synaptic and neuronal signaling is impaired.

## Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder that progressively damages the brain; however, there is currently no cure or easy way to diagnose AD early. This study aims to discover specific differences in gene activity in the brain of AD and identify genes that can serve as risk factors for disease or biomarkers of diagnostic, prognostic, or pharmacological value. Through the re-analysis and meta-analysis of data from multiple existing studies, a combined list of genes that have a statistically significant change in expression was produced. The results showed that genes responsible for communication between brain cells are less active in the AD brain. In contrast, genes involved in the body’s immune defense and inflammation are more active. These findings are valuable as the tracking of these specific gene changes could provide insights into earlier Alzheimer’s diagnosis and improved patient treatment.

Alzheimer’s disease (AD) is the most common neurodegenerative disorder worldwide, for which aging represents the main risk factor. As the global elderly population expands, the prevalence of Alzheimer’s disease escalates rapidly. Notably, as AD brain lesions may start 15–20 years before the appearance of the first symptoms, early diagnosis or prognosis of AD is of paramount importance for better patient treatment. Based on the absence of effective cure or early diagnosis of AD, this meta-analysis investigates the differentially expressed genes between Alzheimer’s and a healthy brain and identifies genes that can serve as risk factors for the disease or biomarkers of diagnostic, prognostic, or pharmacological value. Microarray datasets were collected from public repositories, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. Quality control and data normalization were performed. Differentially expressed gene (DEG) lists were created for each study and combined through a Mosteller–Bush meta-analysis, resulting in a final list of DEGs. This list was filtered using an adjusted p-value cut-off of 0.001, and the included statistically significant DEGs were subjected to enrichment analyses. A total of eight microarray studies were identified, producing a combined list of 4218 DEGs, of which 1944 were up-regulated and enriched for immune response processes, and 2274 were down-regulated and enriched for synapse-related pathways. This meta-analysis reveals a distinct transcriptomic profile in Alzheimer’s disease characterized by the prevalence of immune response and inflammation alongside the collapse of essential synaptic and neuronal signaling.

## Linked entities

- **Diseases:** Alzheimer’s disease (MONDO:0004975)

## Full-text entities

- **Genes:** TREM2 (triggering receptor expressed on myeloid cells 2) [NCBI Gene 54209] {aka AD17, PLOSL2, TREM-2, Trem2a, Trem2b, Trem2c}, OPA1 (OPA1 mitochondrial dynamin like GTPase) [NCBI Gene 4976] {aka BERHS, MGM1, MTDPS14, MTDPS14A, MTDPS14B, NPG}, CDK5 (cyclin dependent kinase 5) [NCBI Gene 1020] {aka LIS7, PSSALRE}, TNFRSF1A (TNF receptor superfamily member 1A) [NCBI Gene 7132] {aka CD120a, FPF, TBP1, TNF-R, TNF-R-I, TNF-R55}, TYROBP (transmembrane immune signaling adaptor TYROBP) [NCBI Gene 7305] {aka DAP12, KARAP, PLOSL, PLOSL1}, GSK3B (glycogen synthase kinase 3 beta) [NCBI Gene 2932], GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, NCSTN (nicastrin) [NCBI Gene 23385] {aka ATAG1874}, Cd2ap (CD2-associated protein) [NCBI Gene 12488] {aka METS-1, Mets1}, GSK3A (glycogen synthase kinase 3 alpha) [NCBI Gene 2931], ADAM10 (ADAM metallopeptidase domain 10) [NCBI Gene 102] {aka AD10, AD18, CD156c, CDw156, HsT18717, MADM}, PSEN1 (presenilin 1) [NCBI Gene 5663] {aka ACNINV3, AD3, CMD1U, FAD, PS-1, PS1}, Rfx1 (regulatory factor X, 1 (influences HLA class II expression)) [NCBI Gene 19724], FAS (Fas cell surface death receptor) [NCBI Gene 355] {aka ALPS1A, APO-1, APT1, CD95, FAS1, FASTM}, NPTXR (neuronal pentraxin receptor) [NCBI Gene 23467] {aka NPR}, CPT1C (carnitine palmitoyltransferase 1C) [NCBI Gene 126129] {aka CATL1, CPT I-C, CPT1-B, CPT1P, CPTI-B, CPTIC}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, CASP8 (caspase 8) [NCBI Gene 841] {aka ALPS2B, CAP4, Casp-8, FLICE, MACH, MCH5}, NDUFB5 (NADH:ubiquinone oxidoreductase subunit B5) [NCBI Gene 4711] {aka CISGDH, SGDH}, NDUFA6 (NADH:ubiquinone oxidoreductase subunit A6) [NCBI Gene 4700] {aka B14, CI-B14, LYRM6, MC1DN33, NADHB14}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, Ms4a4a (membrane-spanning 4-domains, subfamily A, member 4A) [NCBI Gene 666907] {aka EG666907}, SF1 (splicing factor 1) [NCBI Gene 7536] {aka BBP, D11S636, MBBP, ZCCHC25, ZFM1, ZNF162}, BNIP3 (BCL2 interacting protein 3) [NCBI Gene 664] {aka HABON, NIP3}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}, IRF1 (interferon regulatory factor 1) [NCBI Gene 3659] {aka IMD117, IRF-1, MAR}, LMNA (lamin A/C) [NCBI Gene 4000] {aka CDCD1, CDDC, CMD1A, CMT2B1, EMD2, FPL}, CRTAP (cartilage associated protein) [NCBI Gene 10491] {aka CASP, LEPREL3, OI7, P3H5}, App (amyloid beta precursor protein) [NCBI Gene 11820] {aka Abeta, Abpp, Adap, Ag, Cvap, E030013M08Rik}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, PSEN2 (presenilin 2) [NCBI Gene 5664] {aka AD3L, AD4, CMD1V, PS2, STM2}, GSKIP (GSK3B interacting protein) [NCBI Gene 51527] {aka C14orf129, HSPC210}, Acsm3 (acyl-CoA synthetase medium-chain family member 3) [NCBI Gene 20216] {aka Sa, Sah}, Esrra (estrogen related receptor, alpha) [NCBI Gene 26379] {aka ERRalpha, Err1, Estrra, Nr3b1}, Rest (RE1-silencing transcription factor) [NCBI Gene 19712] {aka 2610008J04Rik, NRSF, REST4}, CYCS (cytochrome c, somatic) [NCBI Gene 54205] {aka CYC, HCS, THC4}, MRPL15 (mitochondrial ribosomal protein L15) [NCBI Gene 29088] {aka HSPC145, L15mt, MRP-L15, MRP-L7, RPML7, uL15m}, DNM1L (dynamin 1 like) [NCBI Gene 10059] {aka DLP1, DRP1, DVLP, DYMPLE, EMPF, EMPF1}, CAPN2 (calpain 2) [NCBI Gene 824] {aka CANP2, CANPL2, CANPml, mCANP}, CASP7 (caspase 7) [NCBI Gene 840] {aka CASP-7, CMH-1, ICE-LAP3, LICE2, MCH3}, TRIM63 (tripartite motif containing 63) [NCBI Gene 84676] {aka CMH31, IRF, MURF1, MURF2, RNF28, SMRZ}, PSENEN (presenilin enhancer, gamma-secretase subunit) [NCBI Gene 55851] {aka ACNINV2, MDS033, MSTP064, PEN-2, PEN2}, APH1A (aph-1A gamma-secretase subunit) [NCBI Gene 51107] {aka 6530402N02Rik, APH-1, APH-1A, CGI-78}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, Clu (clusterin) [NCBI Gene 12759] {aka ApoJ, Cli, D14Ucla3, SP-40, Sgp-2, Sgp2}, ROCK1 (Rho associated coiled-coil containing protein kinase 1) [NCBI Gene 6093] {aka P160ROCK, ROCK-I}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}
- **Diseases:** Memory problems (MESH:D008569), cognitive decline (MESH:D003072), neuronal damage (MESH:D009410), type 2 diabetes (MESH:D003924), Dementia (MESH:D003704), brain lesions (MESH:D001927), mental agility (MESH:D008607), metabolic disorders (MESH:D008659), hearing loss (MESH:D034381), synaptic degeneration (MESH:D012183), neurofibrillary tangles (MESH:D055956), obesity (MESH:D009765), stroke (MESH:D020521), Down syndrome (MESH:D004314), neurotoxicity (MESH:D020258), AD (MESH:D000544), brain atrophy (MESH:C566985), neuroinflammation (MESH:D000090862), atrophy (MESH:D001284), brain trauma (MESH:D000070642), Inflammation (MESH:D007249), neurodegeneration (MESH:D019636), injury to (MESH:D014947), IgA glomerulonephritis (MESH:D017098), Mitochondrial damage (MESH:D028361)
- **Chemicals:** calcium (MESH:D002118), ROS (MESH:D017382), citric acid (MESH:D019343), ATP (MESH:D000255), lipid (MESH:D008055), fatty acid (MESH:D005227), luminal calcium (-), cholesterol (MESH:D002784), lecanemab (MESH:C000612089), paraffin (MESH:D010232)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12938635/full.md

## References

124 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938635/full.md

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Source: https://tomesphere.com/paper/PMC12938635