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CD33 isoforms in microglia and Alzheimer's disease: Friend and foe
Ghazaleh Eskandari-Sedighi1, Jaesoo Jung1, Matthew S Macauley2
1Department of Chemistry, University of Alberta, Canada.
Abstract:
Alzheimer's disease (AD) is the most common form of neurodegenerative disease and is considered the main cause of dementia worldwide. Genome-wide association studies combined with integrated analysis of functional datasets support a critical role for microglia in AD pathogenesis, identifying them as important potential therapeutic targets. The ability of immunomodulatory receptors on microglia to control the response to pathogenic amyloid-β aggregates has gained significant interest. Siglec-3, also known as CD33, is one of these immunomodulatory receptors expressed on microglia that has been identified as an AD susceptibility factor. Here, we review recent advances made in understanding the multifaceted roles that CD33 plays in microglia with emphasis on two human-specific CD33 isoforms that differentially correlate with AD susceptibility. We also describe several different therapeutic approaches for targeting CD33 that have been advanced for the purpose of skewing microglial cell responses.
Insights
Alzheimer's disease (AD) involves microglia, immune cells in the brain. CD33, a receptor on microglia, is linked to AD risk, with specific human forms impacting susceptibility. Targeting CD33 offers potential therapeutic strategies.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Alzheimer's disease (AD) is a leading cause of dementia globally.
- Microglia play a crucial role in AD pathogenesis, emerging as therapeutic targets.
- Microglial immunomodulatory receptors, like CD33 (Siglec-3), influence responses to amyloid-β and are AD susceptibility factors.
Purpose of the Study:
- To review recent advances in understanding the roles of CD33 in microglia.
- To emphasize the differential correlation of two human-specific CD33 isoforms with AD susceptibility.
- To describe therapeutic strategies targeting CD33 to modulate microglial responses.
Main Methods:
- Review of recent scientific literature on CD33 and Alzheimer's disease.
- Analysis of genetic association studies and functional datasets related to microglia.
- Examination of therapeutic approaches targeting CD33.
Main Results:
- CD33 is an immunomodulatory receptor on microglia implicated in AD.
- Two human-specific CD33 isoforms show differential correlations with AD susceptibility.
- Targeting CD33 presents potential therapeutic avenues for Alzheimer's disease.
Conclusions:
- CD33 plays a multifaceted role in microglial function relevant to AD.
- Understanding CD33 isoforms is key to developing targeted AD therapies.
- Modulating microglial responses via CD33 offers a promising therapeutic strategy for AD.
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