Microglia and amyloid plaque formation in Alzheimer's disease - Evidence, possible mechanisms, and future challenges

Stefanie Fruhwürth; Henrik Zetterberg; Søren R Paludan

doi:10.1016/j.jneuroim.2024.578342

Microglia and amyloid plaque formation in Alzheimer's disease - Evidence, possible mechanisms, and future challenges

J Neuroimmunol. 2024 May 15:390:578342. doi: 10.1016/j.jneuroim.2024.578342. Epub 2024 Apr 4.

Authors

Stefanie Fruhwürth¹, Henrik Zetterberg², Søren R Paludan³

Affiliations

¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. Electronic address: stefanie.fruhwurth@gu.se.
² Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, Institute of Neurology, University College London Queen Square, London, UK; UK Dementia Research Institute at UCL, London, UK; Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, USA.
³ Department of Rheumatology and Inflammatory Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; Department of Biomedicine, Aarhus University, Aarhus, Denmark. Electronic address: srp@biomed.au.dk.

PMID: 38640827
DOI: 10.1016/j.jneuroim.2024.578342

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive decline that severely affects patients and their families. Genetic and environmental risk factors, such as viral infections, synergize to accelerate the aging-associated neurodegeneration. Genetic risk factors for late-onset AD (LOAD), which accounts for most AD cases, are predominantly implicated in microglial and immune cell functions. As such, microglia play a major role in formation of amyloid beta (Aβ) plaques, the major pathological hallmark of AD. This review aims to provide an overview of the current knowledge regarding the role of microglia in Aβ plaque formation, as well as their impact on morphological and functional diversity of Aβ plaques. Based on this discussion, we seek to identify challenges and opportunities in this field with potential therapeutic implications.

Keywords: Alzheimer's disease; Amyloid plaques; Microglia; Neuroinflammation.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / genetics
Alzheimer Disease* / immunology
Alzheimer Disease* / metabolism
Alzheimer Disease* / pathology
Amyloid beta-Peptides / metabolism
Animals
Humans
Microglia* / metabolism
Microglia* / pathology
Plaque, Amyloid* / metabolism
Plaque, Amyloid* / pathology

Substances

Amyloid beta-Peptides