Emerging Microglia Biology Defines Novel Therapeutic Approaches for Alzheimer’s Disease
Open accessAbstract
Alzheimer's disease (AD) is currently untreatable, and therapeutic strategies aimed to slow cognitive decline have not yet been successful. Many of these approaches have targeted the amyloid cascade, indicating that novel treatment strategies are required. Recent genome-wide association studies (GWASs) have identified a number of risk factors in genes expressed in microglia, underscoring their therapeutic potential in neurodegeneration. In this review, we discuss how the recently defined functions of these AD risk genes can be targeted therapeutically to modulate microglial cell state and slow the progression of AD. Antibody-mediated stimulation of the triggering receptor of myeloid cells 2 (TREM2) is on the forefront of these candidate therapeutic approaches based on a combination of compelling human genetics and emerging preclinical data. This and other approaches to modify microglial function are a topic of intensive study and provide an opportunity for innovative AD treatments, which may be applied alone or potentially in combination with classical anti-amyloid therapies.
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Current evidence points to the enhancement of TREM2 signalling as a promising candidate for AD therapy.
“Current evidence, as described in the previous section, points to the enhancement of TREM2 signalling as a promising candidate for AD therapy [124]”
From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [124]
Several TREM2-targeting drugs are under development, with some approaches at more advanced stages than others.
“Several TREM2-targeting drugs are under development, with some approaches at more advanced stages than others (reviewed in Lewcock et al. [124])”
From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [124]
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- Authors
- Lewcock, J. W., Schlepckow, K., Di Paolo, G., Tahirovic, S., Monroe, K. M., & Haass, C.
- Affiliations
- Denali Therapeutics (United States) (US)
- German Center for Neurodegenerative Diseases (DE)
- Corresponding author
- Lewcock, Joseph W.
- Haass, Christian
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2020-12
- Volume
- 108
- Issue
- 5
- Pages
- 801-821
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W3094301905
- Cited by
- 221
- References
- 74
- Citations by year
- 2026: 24 · 2025: 35 · 2024: 34 · 2023: 42 · 2022: 45 · 2021: 38 · 2020: 3
- FWCI
- 3.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- DZNE Pub (submittedVersion)
- Funders
- Bundesministerium für Bildung und Forschung (01ED2002A)
- NOMIS Stiftung
- Deutsche Forschungsgemeinschaft (390857198, HA1737/16-1)
- Novartis
- Roche
- Alzheimer Forschung Initiative
- Bundesministerium für Bildung, Wissenschaft und Forschung
- EU Joint Programme – Neurodegenerative Disease Research
- European Commission
- Innovative Medicines Initiative (115976)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, microglia, TREM2, microglial activation, Alzheimer's disease risk genes, anti-amyloid therapy, antibody therapy, neurodegeneration, cognitive decline
- MeSH terms
- Alzheimer Disease, Animals, Antibodies, Monoclonal, Brain, Humans, Immunotherapy, Membrane Glycoproteins, Receptors, Immunologic, Genetic Therapy, Microglia, Genome-Wide Association Study
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