Characterization and clinical use of inflammatory cerebrospinal fluid protein markers in Alzheimer’s disease
Open accessAbstract
BACKGROUND: Neuroinflammation has gained increasing attention as a potential contributing factor in Alzheimer's disease (AD) pathology. A clinical cerebrospinal fluid biomarker capable of monitoring this process during the course of the disease has yet to emerge, chiefly owing to contradictory research findings. In this study, we sought to clarify the utility of inflammatory biomarkers in diagnostic procedures of AD in three steps: (1) to screen for proteins that are robustly detectable in cerebrospinal fluid; (2) based on this analysis, to explore any associations between the analytically robust markers and salient pathological features of AD; and (3) to determine the discriminative power of these markers in the clinical diagnosis of AD. METHODS: From a total of 46 proteins, 15 that were robustly detectable in cerebrospinal fluid were identified. A subsequent analysis of these markers in a cohort of 399 patients (nondemented subjects, patients with mild cognitive impairment [MCI], and patients with AD, supplemented by smaller cohorts of other diseases) was conducted. Fluid biomarker data were related to AD pathology and neuropsychological markers and adjusted for confounders such as age, sex, apolipoprotein E genotype, and biobank storage time. RESULTS: Cerebrospinal fluid levels of C-reactive protein and soluble TREM2 differed between nondemented subjects, patients with MCI, or patients with AD and were associated with amyloid and tau pathology. Several markers were associated with tau pathology only or with other neurodegenerative diseases. Correlations between neuropsychological performance and inflammatory markers were weak, but they were most prominent in AD and for the most challenging cognitive tests. All investigated covariates had significant influence, with varying effects across the markers. Still, none of the markers achieved discriminative power of more than 70% to distinguish between patient groups defined by clinical or neuropathological categories. CONCLUSIONS: Basic analytical considerations proved indispensable for this type of study because only one-third of the tested markers were robustly detectable in cerebrospinal fluid. Detectable inflammatory protein markers were associated in multiple ways with AD pathology. Yet, even significantly associated markers were not powerful enough in terms of effect strength, sensitivity, and specificity, and hence they were not suited for direct use in clinical diagnostic practice. Targets other than those most commonly considered in this field of research might provide results with better clinical applicability.
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It is concluded that CSF levels of these markers correspond to the pathological activity in the brain only in the later stages with cognitive demand tasks in Alzheimer's disease.
“It is concluded that CSF levels of these markers correspond to the pathological activity in the brain only in the later stages with cognitive demand tasks in AD [55].”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [55]
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“There are several studies that have reported significantly higher concentrations of the soluble variant of TREM2 (sTREM2) in AD compared to control CSF and significant correlations were observed in CSF between soluble TREM2 and total tau as well as ptau181 (Brosseron et al., 2018; Gispert et al., 2016; Heslegrave et a…”
BackgroundBatista, A. F., Bodart‐Santos, V., Felice, F. G. D., & Ferreira, S. T. (2018) · CNS Drugs · doi:10.1007/s40263-018-0593-6 · Cited by 77 · see citing works
Silva, D. F., Candeias, E., Esteves, A. R., Magalhães, J. D., Ferreira, I. L., Nunes‐Costa, D., Rego, A. C., Empadinhas, N., & Cardoso, S. M. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-02004-y · Cited by 70 · see citing works
“Increased levels of pro-inflammatory markers were detected in the CSF of AD patients, namely IL-8, IL-6, and TREM2 [5, 6], as well as in brain tissue where the activation of microglial cells was assessed by examining CD68 and Iba1 positive cells [7].”
BackgroundTREM2 alters the phagocytic, apoptotic and inflammatory response to Aβ42 in HMC3 cells
Akhter, R., Shao, Y., Formica, S., Khrestian, M., & Bekris, L. M. (2021) · Molecular Immunology · doi:10.1016/j.molimm.2020.12.035 · Cited by 68 · see citing works
Brosseron, F., Maaß, A., Kleineidam, L., Ravichandran, K. A., García‐González, P., McManus, R. M., Ising, C., Santarelli, F., Kolbe, C., Häsler, L. M., et al. (2022) · Neuron · doi:10.1016/j.neuron.2021.12.016 · Cited by 64 · see citing works
Self-citationThe Importance of Complement-Mediated Immune Signaling in Alzheimer’s Disease Pathogenesis
Batista, A. F., Khan, K., Papavergi, M.-T., & Lemere, C. A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25020817 · Cited by 67 · see citing works
“Some evidence indicates that excessive brain inflammation is implicated in the pathogenesis of a number of neurological disorders [36], including AD, where increased levels of inflammatory mediators such as cytokines and chemokines are elevated in patients with the disorder [37,38].”
BackgroundGavrilova, S., & Alvarez, A. (2020) · Medicinal research reviews (Print) · doi:10.1002/med.21722 · Cited by 56 · see citing works
“Reduced CSF levels of VEGF were also reported in subjects with positive tau pathology.(91) Although results of studies on circulating VEGF in AD are inconsistent, Alvarez et al.”
BackgroundBrosseron, F., Maaß, A., Kleineidam, L., Ravichandran, K. A., Kolbe, C., Wolfsgruber, S., Santarelli, F., Häsler, L. M., McManus, R. M., Ising, C., et al. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-022-01118-0 · Cited by 61 · see citing works
Self-citationDecreased CX3CL1 Levels in the Cerebrospinal Fluid of Patients With Alzheimer’s Disease
Perea, J. R., Lleó, A., Alcolea, D. A., Fortea, J., Ávila, J., & Bolós, M. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00609 · Cited by 57 · see citing works
Hegazy, S. H., Thomassen, J. Q., Rasmussen, I. J., Nordestgaard, B. G., Tybjærg‐Hansen, A., & Frikke‐Schmidt, R. (2022) · Alzheimer s & Dementia · doi:10.1002/alz.12568 · Cited by 52 · see citing works
Wu, C., Bawa, K. K., Ouk, M., Leung, N., Yu, D., Lanctôt, K. L., Herrmann, N., Pakosh, M. T., & Swardfager, W. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101130 · Cited by 53 · see citing works
CHIT1 at Diagnosis Reflects Long‐Term Multiple Sclerosis Disease Activity
Oldoni, E., Smets, I., Mallants, K., Vandebergh, M., Van Horebeek, L., Poesen, K., Dupont, P., Dubois, B., & Goris, A. (2020) · Annals of Neurology · doi:10.1002/ana.25691 · Cited by 50 · see citing works
“CSF sTREM2 levels are increased in AD and mild cognitive impairment patients compared with controls and correlate strongly with tau pathology.(45) Although Piccio et al(12) reported elevated sTREM2 levels in MS patients compared to controls, we did not observe any correlation with disease activity.”
BackgroundObrocki, P., Khatun, A., Ness, D., Senkevich, K. A., Hanrieder, J., Capraro, F., Mattsson, N., Andréasson, U., Portelius, E., Ashton, N. J., et al. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00586-6 · Cited by 51 · see citing works
Huang, Z., Hamblin, M. R., & Zhang, Q. (2024) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01484-x · Cited by 50 · see citing works
“Studies in recent years have firmly established neuro-inflammation to be a central player in AD pathogenesis [84, 85].”
BackgroundMulticenter Alzheimer's and Parkinson's disease immune biomarker verification study
Brosseron, F., Kolbe, C., Santarelli, F., Carvalho, S., Antonell, A., Castro‐Gomez, S., Tacik, P., Namasivayam, A. A., Mangone, G., Schneider, R., et al. (2020) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2019.07.018 · Cited by 47 · see citing works
Self-citationSoluble TREM2 and Inflammatory Proteins in Alzheimer’s Disease Cerebrospinal Fluid
Rauchmann, B., Sadlon, A., Perneczky, R., & Initiative, A. D. N. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-191120 · Cited by 49 · see citing works
“IP-10, a biomarker known to be associated with tau pathology [32], was correlated with sTREM2 only in the A+TN+subgroup.”
Knapskog, A., Henjum, K., Idland, A., Eldholm, R. S., Persson, K., Saltvedt, I. T., Watne, L. O., Engedal, K., & Nilsson, L. N. G. (2020) · Scientific Reports · doi:10.1038/s41598-020-72878-8 · Cited by 51 · see citing works
Plasma VEGFA and PGF impact longitudinal tau and cognition in preclinical Alzheimer’s disease
Yang, H., Yau, W. W., Carlyle, B. C., Trombetta, B. A., Zhang, C. M., Shirzadi, Z., Schultz, A. P., Pruzin, J. J., Fitzpatrick, C. D., Kirn, D. R., et al. (2024) · Brain · doi:10.1093/brain/awae034 · Cited by 42 · see citing works
Albrecht, D. S., Sagare, A., Pachicano, M., Sweeney, M. D., Toga, A., Zlokovic, B., Chui, H., Joe, E., Schneider, L., Morris, J. C., et al. (2021) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2021.01.010 · Cited by 37 · see citing works
“, 2018) and in those with mild cognitive impairment and clinical AD (Brosseron et al., 2018).”
BackgroundAdvantages and Pitfalls in Fluid Biomarkers for Diagnosis of Alzheimer’s Disease
Omar, S. H., & Preddy, J. (2020) · Journal of Personalized Medicine · doi:10.3390/jpm10030063 · Cited by 40 · see citing works
“Out of the several investigated inflammatory biomarkers, the diminished C-reactive protein (CRP) level and increased level of triggering receptor expressed on myeloid cells-2 (TREM-2) were observed in the CSF of the patient with AD compared to the normal elderly controls [98].”
Oral microbiome and serological analyses on association of Alzheimer's disease and periodontitis
Fu, K., Chiu, M., Wara‐aswapati, N., Yang, C., Chang, L., Guo, Y. L., Ni, Y., & Chen, Y. (2022) · Oral Diseases · doi:10.1111/odi.14348 · Cited by 38 · see citing works
Inflammatory pathway analytes predicting rapid cognitive decline in MCI stage of Alzheimer’s disease
Pillai, J. A., Bena, J., Bebek, G., Bekris, L. M., Bonner‐Jackson, A., Kou, L., Pai, A., Sørensen, L., Neilsen, M., Rao, S. M., et al. (2020) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51109 · Cited by 34 · see citing works
Bellelli, F., Angioni, D., Arosio, B., Vellas, B. J., & Barreto, P. D. S. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102699 · Cited by 33 · see citing works
Hayek, D., Ziegler, G., Kleineidam, L., Brosseron, F., Nemali, A., Vockert, N., Ravichandran, K. A., Betts, M. J., Peters, O., Schneider, L., et al. (2024) · Molecular Psychiatry · doi:10.1038/s41380-023-02387-3 · Cited by 31 · see citing works
“The resulting tissue maps were quality checked using CAT ’ s sample homogeneity check, which revealed one extreme outlier for GM and one for WM probability maps in our sample, which were excluded from the analyses ( fi nal N = 258).”
BackgroundMethodSelf-citationHuang, D., Wang, Y., Lv, J., Yan, Y., Hu, Y., Liu, C., Zhang, F., Wang, J., & Hao, D. (2020) · PeerJ · doi:10.7717/peerj.9009 · Cited by 30 · see citing works
“Biomedical substances that are involved in metabolic activities are tied to an individual’s biological or metabolic status; thus, circulating proteins are considered sensitive and specific markers of certain pathological states, including abnormal bone metabolism (Brosseron et al., 2018; Shao et al., 2019).”
BackgroundFluid Candidate Biomarkers for Alzheimer’s Disease: A Precision Medicine Approach
Prete, E. D., Beatino, M. F., Campese, N., Giampietri, L., Siciliano, G., Ceravolo, R., & Baldacci, F. (2020) · Journal of Personalized Medicine · doi:10.3390/jpm10040221 · Cited by 27 · see citing works
“Actually, CSF YKL-40 differentiated AD from DLB, PD [160], FTLD [161], and non-AD MCI [162] with only a moderate diagnostic accuracy.”
BackgroundKnowledge gaps in Alzheimer's disease immune biomarker research
Morgan, D., & Mielke, M. M. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12342 · Cited by 25 · see citing works
Daniilidou, M., Holleman, J., Hagman, G., Kåreholt, I., Aspö, M., Brinkmalm, A., Zetterberg, H., Blennow, K., Solomon, A., Kivipelto, M., et al. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-03072-x · Cited by 26 · see citing works
Chen, R., Zhang, Q., Yan, Y., Zhang, Y., & Zhang, T. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-02219-3 · Cited by 24 · see citing works
Advances in neuroimaging to support translational medicine in dementia
Cope, T. E., Weil, R., Düzel, E., Dickerson, B., & Rowe, J. (2021) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2019-322402 · Cited by 17 · see citing works
Wang, R., Zhan, Y., Zhu, W., Yang, Q., & Pei, J. (2024) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2024.1407980 · Cited by 24 · see citing works
Elevated sTREM2 and NFL levels in patients with sepsis associated encephalopathy
Orhun, G., Esen, F., Yılmaz, V., Ulusoy, C. A., Şanlı, E., Yıldırım, E., Gurvit, H. I., Özcan, P. E., Sencer, S., Bebek, N., et al. (2021) · International Journal of Neuroscience · doi:10.1080/00207454.2021.1916489 · Cited by 23 · see citing works
Tau-Mediated Dysregulation of Neuroplasticity and Glial Plasticity
Koller, E. J., & Chakrabarty, P. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00151 · Cited by 22 · see citing works
“elevation is not reliable enough for AD diagnosis, it may be indicative of microglial activity (Suárez-Calvet et al., 2016b; Brosseron et al., 2018).”
BackgroundInfluentialBrosseron, F., Kleemann, K. L., Kolbe, C., Santarelli, F., Castro‐Gomez, S., Tacik, P. M., Latz, E., Jessen, F., & Heneka, M. T. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15175 · Cited by 22 · see citing works
“…previously described as highly related to CSF tau levels in this cohort [macrophage migration inhibitory factor, (MIF), soluble vascular endothelial growth factor receptor (sVEGFR), sTREM2, soluble vascular cell adhesion molecule 1 (sVCAM-1), sICAM-1, and complement C1q) (Brosseron et al., 2018).”
BackgroundMethodInfluentialSelf-citationKumari, E., Xu, A., Chen, R., Yan, Y., Yang, Z. R., & Zhang, T. (2022) · Experimental Neurology · doi:10.1016/j.expneurol.2022.114231 · Cited by 21 · see citing works
Contreras, J. A., Aslanyan, V., Albrecht, D., Mack, W. J., Initiative, A. D. N., & Pa, J. (2022) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12346 · Cited by 20 · see citing works
AMBAR, an Encouraging Alzheimer's Trial That Raises Questions
Loeffler, D. A. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00459 · Cited by 19 · see citing works
Lyu, M., Liu, H., Ye, Y., & Yin, Z. (2020) · Biophysical Chemistry · doi:10.1016/j.bpc.2020.106367 · Cited by 19 · see citing works
Li, T., Initiative, A. D. N., Lyu, D., & Liu, F. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220598 · Cited by 17 · see citing works
Sandoval, C., Lee, J., Toth, B., Nagaraj, R., Schauer, S. P., Hoffman, J. C., Calderon, E., Kollmorgen, G., Bohorquez, S. M. S., Monteiro, C., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14271 · Cited by 18 · see citing works
APOE4 Copy Number-Dependent Proteomic Changes in the Cerebrospinal Fluid1
Berger, M., Cooter, M., Roesler, A. S., Chung, S., Park, J., Modliszeski, J. L., VanDusen, K. W., Thompson, J. W., Moseley, M. A., Devinney, M. J., et al. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200747 · Cited by 15 · see citing works
Burgelman, M., Dujardin, P., Vandendriessche, C., & Vandenbroucke, R. E. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1055050 · Cited by 15 · see citing works
“Conversely, unchanged levels were shown for C1q (39, 40), clusterin (50) and fH (39, 44, 46).”
BackgroundMeyer, P., Savard, M., Poirier, J., Morgan, D., Breitner, J. C. S., & Initiative, A. D. N. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.05.007 · Cited by 15 · see citing works
“We know of no present evidence of similar mechanisms in human studies, notably because these efforts have encountered difficulties in reliable measurement of the most important markers of immune activation in CSF [77,78].”
Zhuo, Y., Fu, X., Jiang, Q., Lai, Y., Gu, Y., Fang, S., Chen, H., Liu, C., Pan, H., Wu, Q., et al. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.175895 · Cited by 15 · see citing works
Ekman, U., Ferreira, D., Muehlboeck, J., Wallert, J., Rennie, A., Eriksdotter, M., Wahlund, L., & Westman, E. (2020) · BMC Geriatrics · doi:10.1186/s12877-020-1478-3 · Cited by 15 · see citing works
Increased YKL-40 but Not C-Reactive Protein Levels in Patients with Alzheimer’s Disease
Blanco-Palmero, V. A., Rubio‐Fernández, M., Antequera, D., Villarejo‐Galende, A., Pérez-Molina, J. A., Ferrer, I., Bartolomé, F. B., & Carro, E. (2021) · Biomedicines · doi:10.3390/biomedicines9091094 · Cited by 15 · see citing works
“Furthermore, the CRP levels in CSF remained unchanged in PD patients when compared with healthy subjects [26,32].”
BackgroundResultSabbagh, M. N., Cummings, J. L., Ballard, C. G., van der Flier, W. M., Heneka, M. T., Holst, J. J., Knudsen, L. B., Salloway, S., Tansey, M. G., & Drucker, D. J. (2025) · Nature Aging · doi:10.1038/s43587-025-01029-3 · Cited by 14 · see citing works
“%) were white; and 59.7% and 54.5% were receiving AD medication, respectively.”
InfluentialSelf-citationInflammation in the CNS: Understanding Various Aspects of the Pathogenesis of Alzheimer's Disease
Doroszkiewicz, J., Mroczko, P., & Kulczyńska‐Przybik, A. (2021) · Current Alzheimer Research · doi:10.2174/1567205018666211202143935 · Cited by 14 · see citing works
Pan, R., Luo, S.-Y., Huang, Q., Li, W.-W., Cai, T.-G., Lai, K., & Shi, X. (2022) · Journal of Alzheimer's Disease · doi:10.3233/jad-220002 · Cited by 12 · see citing works
Moyse, E., Haddad, M., Benlabiod, C., Ramassamy, C., & Krantic, S. M. (2019) · Current Alzheimer Research · doi:10.2174/1567205016666191106094356 · Cited by 13 · see citing works
Zhou, W., Zhou, Y., & Li, J. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12103589 · Cited by 12 · see citing works
Predicting neurodegeneration from sleep related biofluid changes
Yang, Y., Kim, W. S., Michaelian, J. C., Lewis, S. J. G., Phillips, C. L., D'Rozario, A. L., Chatterjee, P., Martins, R. N., Grunstein, R. R., Halliday, G. M., et al. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106369 · Cited by 10 · see citing works
“They have also been shown to be increased in MCI and dementia (Brosseron et al., 2018; Darweesh et al., 2018; Havekes et al., 2019; Swardfager et al., 2010), and also cognitively unimpaired older adults with higher self-reported sleepiness scores (Carvalho et al., 2022).”
BackgroundBeyond amyloid: nanobody-mediated neuroinflammatory therapy for Alzheimer’s disease
Amniouel, S., Suh, J., Zheng, W. H., & Zhang, Q. (2025) · Translational Neurodegeneration · doi:10.1186/s40035-025-00513-5 · Cited by 11 · see citing works
“To address the concern of silencing necessary immune responses, our proposed therapy aims to target specific inflammatory mediators that are known to be deleterious in AD such as IL-1β and TNF-α [45, 46], while preserving the beneficial functions of microglia and astrocytes.”
Pilot proteomic analysis of cerebrospinal fluid in Alzheimer's disease
McKetney, J., Panyard, D. J., Johnson, S. C., Carlsson, C. M., Engelman, C. D., & Coon, J. J. (2021) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.202000072 · Cited by 9 · see citing works
Teipel, S. J., Dyrba, M., Kleineidam, L., Brosseron, F., Levin, F., Bruno, D., Büerger, K., Cosma, N. C., Schneider, L., Düzel, E., et al. (2024) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12510 · Cited by 8 · see citing works
Self-citationCerebrospinal Fluid Inflammatory Markers in Alzheimer’s Disease: Influence of Comorbidities
Wang, Y., Emre, C., Gyllenhammar-Schill, H., Fjellman, K., Eyjolfsdottir, H., Eriksdotter, M., Schultzberg, M., & Hjorth, E. (2021) · Current Alzheimer Research · doi:10.2174/1567205018666210330162207 · Cited by 8 · see citing works
Hu, S., Pan, N., Liu, C., Wang, Y., & Zhang, T. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.775432 · Cited by 8 · see citing works
Phadke, L., Lau, D. H. W., Aghaizu, N. D., Ibarra, S., Navarrón, C. M., Granat, L., Magno, L., Whiting, P. J., & Jolly, S. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1056067 · Cited by 8 · see citing works
“In addition, studies have found that elevated levels of inflammatory markers are present in patients with AD (Brosseron et al., 2018), and a number of AD risk genes are associated with innate immune functions (Efthymiou and Goate, 2017; Bellenguez et al.”
BackgroundSoluble TREM2 in body fluid in Alzheimer’s disease and Parkinson’s disease
Gu, L., Shu, H., & Wang, Y. (2023) · Neurological Sciences · doi:10.1007/s10072-023-06729-5 · Cited by 7 · see citing works
“N = 7 studies (including 531 AD patients and 553 HCs) [13, 14, 16, 19, 20, 26, 37] compared sTREM2 level in plasma between AD patients and HCs.”
ResultSexual dimorphisms in innate immune activation markers in predementia Alzheimer’s disease
Knudtzon, S. L., Nordengen, K., Pålhaugen, L., Gísladóttir, B., Jarholm, J. A., Bråthen, G., Skogseth, R. E., Waterloo, K. K., Selnes, P., Fladby, T., et al. (2025) · Brain Communications · doi:10.1093/braincomms/fcaf161 · Cited by 7 · see citing works
“24 found that males had significantly higher concentrations of several inflammatory CSF proteins, including MCP-1 and IL-6, consistent with our results.”
InfluentialAlilou, S., Valizadeh, P., KamaliZonouzi, S., Salabat, D., Jannatdoust, P., Amanollahi, M., Rashidi, F., Rezaie, S., Delavari, S., & Aarabi, M. H. (2024) · Brain Behavior and Immunity Integrative · doi:10.1016/j.bbii.2024.100092 · Cited by 7 · see citing works
Microglia protein profiles in CSF across Alzheimer’s disease clinical stages
Blujdea, E. R., van Bokhoven, P., Adami, P. V. M., Marshe, V. S., Vromen, E., Hok‐A‐Hin, Y. S., Boiten, W. A., Irwin, D. J., Chen‐Plotkin, A. S., Lemstra, A. W., et al. (2026) · Nature Aging · doi:10.1038/s43587-026-01088-0 · Cited by 7 · see citing works
“26–30), MIF 27 and sAXL 10 , that are elevated in earlier stages of AD, possibly as a protective response to the accumulation of amyloid pathology 10,25,28,31–33 .”
Self-citationGhanbarian, E., Khorsand, B., Petersen, K. K., Nallapu, B. T., Sajjadi, S. A., Lipton, R. B., Ezzati, A., & Initiative, A. D. N. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251335915 · Cited by 8 · see citing works
“11 However, studies examining the association between CSF in fl ammatory markers and the progression of cognitive decline over time have produced inconsistent and sometimes con fl icting results.”
CSF biomarkers of neuroinflammation are associated with regional atrophy
Özlü, S., Dyrba, M., Grazia, A., Brosseron, F., Büerger, K., Dechent, P., Düzel, E., Ewers, M., Fließbach, K., Glanz, W., et al. (2025) · Journal of Neurology · doi:10.1007/s00415-025-13564-5 · Cited by 3 · see citing works
Self-citationBifurcations in coupled amyloid-β aggregation-inflammation systems
Chakrabarti, K. S., Bakhtiari, D., & Rezaei‐Ghaleh, N. (2024) · npj Systems Biology and Applications · doi:10.1038/s41540-024-00408-7 · Cited by 3 · see citing works
Gutierrez, J., Kurz, C., Sandoval, C., Edmonds, R., Bittner, T., Perneczky, R., & Biever, A. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-240287 · Cited by 3 · see citing works
“3 – 8 This suggests that neuroinflammation represents a third pathological hallmark of AD, although it is controversial whether immune cells exert beneficial or detrimental activities in the pathogenesis of AD.”
BackgroundMethodSex differences in CSF biomarkers of Alzheimer’s disease
Mielke, M. M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819344-0.00012-0 · Cited by 4 · see citing works
Recent Advances in Neurodegeneration
Borreca, A. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.71995 · Cited by 3 · see citing works
Ghanbarian, E., Khorsand, B., Petersen, K. K., Nallapu, B. T., Sajjadi, S. A., Lipton, R. B., & Ezzati, A. (2024) · medRxiv · doi:10.1101/2024.11.13.24317270 · Cited by 3 · see citing works
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Tubi, M. A., Wheeler, K. V., Matsiyevskiy, E., Hapenney, M., Mack, W. J., Chui, H. C., King, K. S., Thompson, P. M., & Braskie, M. N. (2023) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2023.08.002 · Cited by 2 · see citing works
Molecular Basis of Neurodegeneration: Lessons from Alzheimer’s and Parkinson’s Diseases
Zolezzi, J. M., Candia, S. B., & Inestrosa, N. C. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.81270 · Cited by 2 · see citing works
Linking evidence for targeted blood biomarkers in post-stroke cognitive impairment and dementia
Hong, J., Mun, K. T., Kern, K. C., Thirion, M. L., & Hinman, J. D. (2025) · Frontiers in Stroke · doi:10.3389/fstro.2024.1491542 · Cited by 1 · see citing works
Yu, R., Suraev, A. S., Vidal, V., Kong, S. D., Zachariae, R. H., Piccio, L. M., Heneka, M. T., Naismith, S. L., & Michaelian, J. C. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03787-x · Cited by 1 · see citing works
Self-citationAzadovich, A. P., Oralov, B., Sherzod, K., Kudeshova, G. T., Akmalovna, A. F., Tajimuratovna, B. U., Kambarova, O., Raupov, F., Baxtiyor, S., Jurabek, Y., et al. (2026) · Clinica Chimica Acta · doi:10.1016/j.cca.2026.121010 · Cited by 1 · see citing works
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Kozloski, G. A. (2019) · Materials and Methods · doi:10.13070/mm.en.9.2758
Kozloski, G. A. (2019) · Materials and Methods · doi:10.13070/mm.en.9.2844
Emerging Roles of TREM2 in Neurodegenerative Diseases
Kabir, M. T. (2022) · Springer eBooks · doi:10.1007/978-981-16-7606-2_7
- Authors
- Brosseron, F., Traschütz, A., Widmann, C. N., Kummer, M. P., Tacik, P., Santarelli, F., Jessen, F., & Heneka, M. T.
- Affiliations
- German Center for Neurodegenerative Diseases (DE)
- University of Bonn (DE)
- University of Cologne (DE)
- Corresponding author
- Heneka, Michael T.
- ORCID
- Venue
- Alzheimer's Research & Therapy
- Published
- 2018-02-26
- Volume
- 10
- Issue
- 1
- Pages
- 25-25
- ISSN
- 1758-9193 (ISSN-L)
- PMC
- PMC5828084
- OpenAlex
- W2796088161
- Cited by
- 113
- References
- 51
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 16 · 2023: 10 · 2022: 12 · 2021: 16 · 2020: 29 · 2019: 10 · 2018: 5
- FWCI
- 11.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Alzheimer s Research & Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- Open Repository and Bibliography (University of Luxembourg) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DZNE Pub (submittedVersion, cc-by)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
- Funders
- EU/EFPIA/(Associated Partner) Innovative Medicines Initiative (2) Joint Undertaking (115568)
- European Union’s Seventh Framework Programme (FP7/2007-2013)
- INMiND (HEALTH-F2-2011-278850 TP21)
- Deutsche Forschungsgemeinschaft (KFO177, TP4)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, cerebrospinal fluid biomarkers, neuroinflammation, inflammatory proteins, C-reactive protein, soluble TREM2, amyloid pathology, tau pathology, mild cognitive impairment, diagnostic accuracy, apolipoprotein E
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, C-Reactive Protein, Cerebrospinal Fluid Proteins, Female, Humans, Male, Membrane Glycoproteins, Middle Aged, Receptors, Immunologic, Cohort Studies, Cytokines, Amyloid beta-Peptides, tau Proteins, Statistics, Nonparametric, Vascular Endothelial Growth Factor A
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