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M2b macrophage subset decrement as an indicator of cognitive function in Alzheimer's disease
Sun-Wung Hsieh1,2,3, Ling-Chun Huang2,3,4, Yang-Pei Chang2,3,4
1Department of Neurology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Aim:
Alzheimer's disease (AD) is a chronic neurodegenerative disease. Various inflammatory processes account for the pathology of AD, and macrophages in particular have a distinct polarization phenotype related to M1/M2 classification. We aimed to investigate macrophage polarization patterns as an indicator of cognitive function in AD.
Methods:
We recruited 54 non-demented individuals as control and 105 AD patients as experimental groups respectively. Percentages of macrophage (PM2K+ CD14+ and PM2K+ CD14- ) and macrophage polarization subsets (M1, M2a, M2b, and M2c) were assessed using flow cytometry. All AD patients were classified by dementia severity using clinical Dementia Rating scale (CDR) as CDR 0.5, 1 and ≧2. AD patients had cognitive function evaluation using Mini-Mental State Examination (MMSE) and Cognitive Assessment Screening Instrument (CASI). We compared the macrophage polarization patterns between control and patient groups. Cognitive function was evaluated in association with macrophage polarization patterns in AD patients.
Results:
The percentages of PM2K+ CD14+ and PM2K+ CD14- macrophages were higher in AD patients than in controls. M2b macrophage subset decrement and M1 macrophage subset increment of PM2K+ CD14+ and PM2K+ CD14- macrophages were observed in AD patients compared with controls. Although percentages of macrophage subsets were not consistent with CDR staging, PM2K+ CD14+ M2b macrophage subset decrement was correlated with worse cognitive functioning by MMSE and CASI in AD patients.
Conclusion:
M2b macrophage subset decrement and M1 macrophage subset increment were noted in AD patients, while PM2K+ CD14+ M2b macrophage subset decrement indicated worse cognitive function in such patients.
Insights
Reduced M2b macrophages and increased M1 macrophages are observed in Alzheimer's disease (AD). Lower levels of PM2K+ CD14+ M2b macrophages correlate with poorer cognitive function in AD patients.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Alzheimer's disease (AD) involves complex inflammatory processes.
- Macrophages exhibit distinct M1/M2 polarization phenotypes crucial in AD pathology.
Purpose of the Study:
- To investigate macrophage polarization patterns in Alzheimer's disease.
- To assess the correlation between macrophage polarization and cognitive function in AD patients.
Main Methods:
- Flow cytometry was used to analyze macrophage (PM2K+ CD14+ and PM2K+ CD14-) and polarization subset (M1, M2a, M2b, M2c) percentages.
- Cognitive function was evaluated using MMSE and CASI, and dementia severity was staged using CDR.
- Macrophage polarization patterns were compared between 54 controls and 105 AD patients.
Main Results:
- AD patients showed increased percentages of PM2K+ CD14+ and PM2K+ CD14- macrophages compared to controls.
- A decrease in M2b and an increase in M1 macrophage subsets were observed in AD patients.
- A decrement in PM2K+ CD14+ M2b macrophages correlated with lower MMSE and CASI scores in AD patients.
Conclusions:
- Alzheimer's disease is characterized by reduced M2b and increased M1 macrophage polarization.
- The reduction in PM2K+ CD14+ M2b macrophages serves as an indicator of diminished cognitive function in AD.

