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ApoE4 makes microglia trem2bling
1Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg; Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, North Worcester, MA, USA.
Abstract:
The ApoE-Trem2 pathway links two of the most important genetic risk variants for sporadic Alzheimer's disease. In this issue of Neuron, Gratuze and colleagues1 report that Trem2 deficiency further aggravates neurodegeneration in tau mutant mice expressing human ApoE4. Together with previous work, this study points to a complex interaction and highlights the need for studying molecular interactions on all human ApoE variants.
Insights
The ApoE-Trem2 pathway is crucial for Alzheimer's disease risk. Trem2 deficiency worsens neurodegeneration in mice carrying the ApoE4 gene, indicating a complex genetic interaction.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- The apolipoprotein E (ApoE) and triggering receptor expressed on myeloid cells 2 (Trem2) pathways are implicated in sporadic Alzheimer's disease (AD) genetics.
- Genetic variants in ApoE and Trem2 are significant risk factors for developing AD.
Purpose of the Study:
- To investigate the functional interaction between the ApoE-Trem2 pathway in the context of Alzheimer's disease pathogenesis.
- To determine the impact of Trem2 deficiency on neurodegeneration in a model expressing a high-risk human ApoE variant.
Main Methods:
- Utilized a mouse model expressing human ApoE4 with tau mutations.
- Assessed the effects of Trem2 deficiency on neurodegenerative processes within this model.
Main Results:
- Trem2 deficiency exacerbated neurodegeneration in tau mutant mice expressing human ApoE4.
- This suggests a significant interplay between Trem2 and ApoE4 in AD pathology.
Conclusions:
- The ApoE-Trem2 pathway exhibits complex interactions relevant to Alzheimer's disease.
- Future research should consider the impact of all human ApoE variants on these molecular interactions.
