Alzheimer's disease-associated CD83(+) microglia are linked with increased immunoglobulin G4 and human cytomegalovirus in the gut, 2024, Reiman et al

Alzheimer's disease-associated CD83(+) microglia are linked with increased immunoglobulin G4 and human cytomegalovirus in the gut, vagal nerve, and brain
https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.14401

Abstract

INTRODUCTION
While there may be microbial contributions to Alzheimer's disease (AD), findings have been inconclusive. We recently reported an AD-associated CD83(+) microglia subtype associated with increased immunoglobulin G4 (IgG4) in the transverse colon (TC).

METHODS
We used immunohistochemistry (IHC), IgG4 repertoire profiling, and brain organoid experiments to explore this association.

RESULTS
CD83(+) microglia in the superior frontal gyrus (SFG) are associated with elevated IgG4 and human cytomegalovirus (HCMV) in the TC, anti-HCMV IgG4 in cerebrospinal fluid, and both HCMV and IgG4 in the SFG and vagal nerve. This association was replicated in an independent AD cohort. HCMV-infected cerebral organoids showed accelerated AD pathophysiological features (Aβ42 and pTau-212) and neuronal death.

DISCUSSION
Findings indicate complex, cross-tissue interactions between HCMV and the adaptive immune response associated with CD83(+) microglia in persons with AD. This may indicate an opportunity for antiviral therapy in persons with AD and biomarker evidence of HCMV, IgG4, or CD83(+) microglia.

Highlights

• Cross-tissue interaction between HCMV and the adaptive immune response in a subset of persons with AD.
• Presence of CD83(+) microglial associated with IgG4 and HCMV in the gut.
• CD83(+) microglia are also associated presence of HCMV and IgG4 in the cortex and vagal nerve.
• Replication of key association in an independent cohort of AD subjects.
• HCMV infection of cerebral organoids accelerates the production of AD neuropathological features.

 

PolyBio posted on Bluesky:

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1/ BREAKING A new study published in Nature Communications has unveiled a crucial connection between chronic #infection with Cytomegalovirus (HCMV), and the development of #Alzheimer’s disease in certain individuals: polybio.org/new-research...

2/ The research, led by a team of scientists at Arizona State University who are part of PolyBio's research network, suggests that in some individuals, HCMV may remain active in the #gut.

3/ From there, the virus may travel to the brain via the #vagus nerve, where it is detected by the brain’s immune cells, called microglia. These cells activate the expression of a specific gene, CD83, which may play a role in the biological changes that lead to #Alzheimer’s.

4/ To build on the findings, the researchers hope to determine if widely-available #antiviral medication could help treat or prevent this form of Alzheimer’s disease.

5/ Via this PolyBio project, they are currently working on developing a blood test to identify individuals with an active HCMV infection who could optimally benefit from antiviral treatment: polybio.org/projects/val...