# Inflammatory Mediators of Alzheimer’s Disease Characterized in a Mouse Model (APP/PS1)

**Authors:** Adrian Jorda, Kenia Alvarez-Gamez, Ignacio Campo-Palacio, Juan Campos-Campos, Carlos Colmena, Sandeep Kumar Singh, Maria Jose Chiva Miralles, Constanza Aldasoro, Martin Aldasoro, Soraya L. Valles

PMC · DOI: 10.3390/neurosci7010023 · NeuroSci · 2026-02-06

## TL;DR

This study explores how specific inflammatory molecules are altered in a mouse model of Alzheimer's disease, potentially offering new insights into disease mechanisms and biomarkers.

## Contribution

The study identifies specific chemokine and receptor expression changes in an Alzheimer's mouse model, suggesting novel biomarkers and therapeutic targets.

## Key findings

- Levels of CCL8 and CCL19, along with their receptors, were significantly decreased in APP/PS1 mice.
- CCL6, CCL24, CCL20, and CCL27, along with their receptors, were notably increased in the mouse model.
- Altered chemokine expression may serve as biomarkers for early detection and monitoring of Alzheimer's disease.

## Abstract

Alzheimer’s disease (AD) is marked by amyloid plaques, hyperphosphorylated TAU proteins, and neuroinflammation. The APP/PS1 mouse model is widely used to study AD pathogenesis. In this study, we investigated the expression of chemokines and their receptors, which may play a role in AD’s pathological mechanisms, using brain cortex tissue from female APP/PS1 mice aged 20–21 months. We analyzed several chemokine receptors (CCR1, CCR2, CCR3, CCR4, CCR6, CCR7, CCR9, and CCR10) by Western blot and focused on CCR6, CCR7, and CCR10 using RT-PCR. Additionally, we quantified the levels of chemokines (CCL6, CCL8, CCL19, CCL20, CCL24, and CCL27) by RT-PCR. Our results showed a significant decrease in CCL8 and CCL19, along with their respective receptors, in the APP/PS1 mice compared to controls. On the other hand, we observed a notable increase in CCL6, CCL24, CCL20, CCL27, and their receptors. Chemokines like CCL8 and CCL20, involved in inflammatory responses, may reveal how neuroinflammation contributes to AD. CCL19 and CCL27 are linked to immune cell trafficking, which may help explain immune cell interactions with amyloid plaques and TAU tangles in the CNS. Overall, the altered expression of chemokines such as CCL24 could serve as biomarkers for early AD detection and monitoring disease progression. These findings suggest potential therapeutic targets to modulate immune responses and reduce neuroinflammation in AD.

## Linked entities

- **Genes:** APP (amyloid beta precursor protein) [NCBI Gene 351], PSEN1 (presenilin 1) [NCBI Gene 5663], CCR1 (C-C motif chemokine receptor 1) [NCBI Gene 1230], CCR2 (C-C motif chemokine receptor 2) [NCBI Gene 729230], CCR3 (C-C motif chemokine receptor 3) [NCBI Gene 1232], CCR4 (C-C motif chemokine receptor 4) [NCBI Gene 1233], CCR6 (C-C motif chemokine receptor 6) [NCBI Gene 1235], CCR7 (C-C motif chemokine receptor 7) [NCBI Gene 1236], CCR9 (C-C motif chemokine receptor 9) [NCBI Gene 10803], CCR10 (C-C motif chemokine receptor 10) [NCBI Gene 2826], Ccl6 (C-C motif chemokine ligand 6) [NCBI Gene 20305], CCL8 (C-C motif chemokine ligand 8) [NCBI Gene 6355], CCL19 (C-C motif chemokine ligand 19) [NCBI Gene 6363], CCL20 (C-C motif chemokine ligand 20) [NCBI Gene 6364], CCL24 (C-C motif chemokine ligand 24) [NCBI Gene 6369], CCL27 (C-C motif chemokine ligand 27) [NCBI Gene 10850]
- **Proteins:** MAPT (microtubule associated protein tau)
- **Diseases:** Alzheimer’s disease (MONDO:0004975)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** CCL4 (C-C motif chemokine ligand 4) [NCBI Gene 6351] {aka ACT2, AT744.1, G-26, HC21, LAG-1, LAG1}, Ccr3 (C-C motif chemokine receptor 3) [NCBI Gene 12771] {aka CC-CKR3, CKR3, Cmkbr1l2, Cmkbr3}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, Lifr (LIF receptor alpha) [NCBI Gene 16880] {aka A230075M04Rik, LIF}, Ccr4 (C-C motif chemokine receptor 4) [NCBI Gene 12773] {aka C-C CKR-4, CHEMR1, Cmkbr4, LESTR, Sdf1r}, Ccl17 (C-C motif chemokine ligand 17) [NCBI Gene 20295] {aka Abcd-2, Scya17, Scya17l, Tarc}, Ccl20 (C-C motif chemokine ligand 20) [NCBI Gene 20297] {aka CKb4, LARC, MIP-3A, MIP-3[a], MIP3A, ST38}, CCL3 (C-C motif chemokine ligand 3) [NCBI Gene 6348] {aka G0S19-1, LD78, LD78ALPHA, MIP-1-alpha, MIP1A, SCI}, CCL27 (C-C motif chemokine ligand 27) [NCBI Gene 10850] {aka ALP, CTACK, CTAK, ESKINE, ILC, PESKY}, Cdk5 (cyclin dependent kinase 5) [NCBI Gene 12568] {aka Crk6}, CCL20 (C-C motif chemokine ligand 20) [NCBI Gene 6364] {aka CKb4, Exodus, LARC, MIP-3-alpha, MIP-3a, MIP3A}, Ccr10 (C-C motif chemokine receptor 10) [NCBI Gene 12777] {aka C-C CKR-10, CC-CKR-10, CCR-10, Cmkbr9, Gpr2}, Ccl25 (C-C motif chemokine ligand 25) [NCBI Gene 20300] {aka A130072A22Rik, CKb15, Scya25, TECK}, Il1 (interleukin 1 complex) [NCBI Gene 111343] {aka Il-1}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Ccr9 (C-C motif chemokine receptor 9) [NCBI Gene 12769] {aka A130091K22Rik, Cmkbr10, GPR-9-6}, Aqp4 (aquaporin 4) [NCBI Gene 11829] {aka WCH4}, Gsk3b (glycogen synthase kinase 3 beta) [NCBI Gene 56637] {aka 7330414F15Rik, 8430431H08Rik, GSK-3, GSK-3beta, GSK3}, CXCL12 (C-X-C motif chemokine ligand 12) [NCBI Gene 6387] {aka IRH, PBSF, SCYB12, SDF1, TLSF, TPAR1}, Ccr7 (C-C motif chemokine receptor 7) [NCBI Gene 12775] {aka CC-CKR-7, CCR-7, CD197, Cdw197, Cmkbr7, EBI1}, CCL24 (C-C motif chemokine ligand 24) [NCBI Gene 6369] {aka Ckb-6, MPIF-2, MPIF2, SCYA24}, Actb (actin, beta) [NCBI Gene 11461] {aka Actx, E430023M04Rik, beta-actin}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, App (amyloid beta precursor protein) [NCBI Gene 11820] {aka Abeta, Abpp, Adap, Ag, Cvap, E030013M08Rik}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, Ccl1 (C-C motif chemokine ligand 1) [NCBI Gene 20290] {aka I-309, P500, Scya1, Tca-3, Tca3}, Ccl24 (C-C motif chemokine ligand 24) [NCBI Gene 56221] {aka CKb-6, MPIF-2, Scya24}, Ccr1 (C-C motif chemokine receptor 1) [NCBI Gene 12768] {aka Cmkbr1, Mip-1a-R}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Ccl26 (C-C motif chemokine ligand 26) [NCBI Gene 541307] {aka Ccl26l}, Ccl19 (C-C motif chemokine ligand 19) [NCBI Gene 24047] {aka CKb11, ELC, Gm2023, MIP3B, Scya19, exodus-3}, Tgfa (transforming growth factor alpha) [NCBI Gene 21802] {aka wa-1, wa1}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, Ccl7 (C-C motif chemokine ligand 7) [NCBI Gene 20306] {aka MCP-3, Scya7, fic, marc, mcp3}, Ccl27a (C-C motif chemokine ligand 27A) [NCBI Gene 20301] {aka ALP, CTACK, CTAK, Ccl27, ESkine, ILC}, Il13 (interleukin 13) [NCBI Gene 16163] {aka Il-13}, Ccr2 (C-C motif chemokine receptor 2) [NCBI Gene 12772] {aka Cc-ckr-2, Ccr2a, Ccr2b, Ckr2, Ckr2a, Ckr2b}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, CCR8 (C-C motif chemokine receptor 8) [NCBI Gene 1237] {aka CC-CKR-8, CCR-8, CDw198, CKRL1, CMKBR8, CMKBRL2}, Il17c (interleukin 17C) [NCBI Gene 234836] {aka IL-17C}, Il4 (interleukin 4) [NCBI Gene 16189] {aka BSF-1, Il-4}, Ccr6 (C-C motif chemokine receptor 6) [NCBI Gene 12458] {aka CC-CKR-6, CCR-6, Cmkbr6, KY411}, Ccl6 (C-C motif chemokine ligand 6) [NCBI Gene 20305] {aka MRP-1, Scya6, c10}, Gpr34 (G protein-coupled receptor 34) [NCBI Gene 23890] {aka Lypsr1}, Ccl11 (C-C motif chemokine ligand 11) [NCBI Gene 20292] {aka Scya11, eotaxin}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, Cxcl10 (C-X-C motif chemokine ligand 10) [NCBI Gene 15945] {aka C7, CRG-2, INP10, IP-10, IP10, Ifi10}, Ccl4 (C-C motif chemokine ligand 4) [NCBI Gene 20303] {aka AT744.1, Act-2, MIP-1B, Mip1b, Scya4}, CCL19 (C-C motif chemokine ligand 19) [NCBI Gene 6363] {aka CKb11, ELC, MIP-3b, MIP3B, SCYA19}, Ccl8 (C-C motif chemokine ligand 8) [NCBI Gene 20307] {aka 1810063B20Rik, HC14, MCP-2, Mcp2, Scya8}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Ccr5 (C-C motif chemokine receptor 5) [NCBI Gene 12774] {aka AM4-7, CD195, Cmkbr5}, Ccl5 (C-C motif chemokine ligand 5) [NCBI Gene 20304] {aka MuRantes, RANTES, SISd, Scya5, TCP228}, Mcpt4 (mast cell protease 4) [NCBI Gene 17227] {aka MMCP-4, MMCP-4A, MMCP-4B, Mcp-4, Mcp4}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, Ccl22 (C-C motif chemokine ligand 22) [NCBI Gene 20299] {aka ABCD-1, DCBCK, MDC, Scya22}, Tnfsf12 (tumor necrosis factor (ligand) superfamily, member 12) [NCBI Gene 21944] {aka Apo3l, Dr3l, Dr3lg, Tweak}, Psen1 (presenilin 1) [NCBI Gene 19164] {aka Ad3h, PS-1, PS1, S182}, Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 20296] {aka HC11, JE, MCAF, MCP-1, MCP1, SMC-CF}
- **Diseases:** kidney cancer (MESH:D007680), TAU (MESH:D057180), hepatocellular carcinoma (MESH:D006528), multiple sclerosis lesions (MESH:D009103), HIV-1 infection (MESH:D015658), deficits in (MESH:D009461), synaptic dysfunction (MESH:C536122), synaptic damage (MESH:D012183), ulcerative colitis (MESH:D003093), cognitive decline (MESH:D003072), inflammatory bowel diseases (MESH:D015212), breast cancer (MESH:D001943), autoimmune diseases (MESH:D001327), type 2 diabetes (MESH:D003924), neuronal death (MESH:D009410), allergic (MESH:D004342), amyloid (MESH:C000718787), dementia (MESH:D003704), learning and (MESH:D007859), cancer (MESH:D009369), immunological diseases (MESH:D007154), diabetes (MESH:D003920), lung cancer (MESH:D008175), Crohn's disease (MESH:D003424), AD (MESH:D000544), insulin resistance (MESH:D007333), neuroinflammation (MESH:D000090862), type 3 diabetes (MESH:C566342), metastasis (MESH:D009362), melanoma (MESH:D008545), astrogliosis (MESH:D005911), Inflammatory (MESH:D007249), neurodegeneration (MESH:D019636), injury to (MESH:D014947), pancreatic cancer (MESH:D010190), colorectal cancer (MESH:D015179), cervical cancer (MESH:D002583), demyelination (MESH:D003711), brain injuries (MESH:D001930)
- **Chemicals:** SDS (MESH:D012967), TBS-T (MESH:C027647), ROS (MESH:D017382), TRIzol (MESH:C411644), LPS (MESH:D008070)
- **Species:** Human immunodeficiency virus 1 (no rank) [taxon 11676], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** B6C3 — Mus musculus (Mouse), Hybridoma (CVCL_C2DD)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12921763/full.md

## References

73 references — full list in the complete paper: https://tomesphere.com/paper/PMC12921763/full.md

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Source: https://tomesphere.com/paper/PMC12921763