Cited by 221Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

Emerging Microglia Biology Defines Novel Therapeutic Approaches for Alzheimer’s Disease

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Lewcock, Joseph W., Schlepckow, Kai, Di Paolo, Gilbert, Tahirovic, Sabina, Monroe, Kathryn M., Haass, Christian·2020·Neuron

Abstract

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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Crossref · 10.1016/j.neuron.2020.09.029

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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
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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