Study Links Cytomegalovirus to a Specific Subtype of Alzheimer’s Disease: Could Treating the Virus Offer a Solution?

Researchers from Arizona State University just revealed a surprising link between a common virus, present in most octogenarians, and a specific form of Alzheimer’s disease.

Alzheimer's

Alzheimer’s

Could the key to combating Alzheimer’s lie within our gut microbiome? In the intestines of certain patients may lurk an unexpected suspect: human cytomegalovirus (HCMV), a virus that could silently contribute to the neurodegenerative disease. While the role of microbes in Alzheimer’s has long been suspected, this new study highlights an association between HCMV and a specific form of the disease.

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A Subtype of Alzheimer’s Linked to a Common Virus

HCMV, a viral infection affecting nearly 80% of adults over 80, appears to play a significant role in a unique subtype of Alzheimer’s. Researchers from Arizona State University identified a connection between specific immune cells, known as CD83(+) microglia, and elevated levels of an antibody called immunoglobulin G4 (IgG4) in the colon, vagus nerve, and brain tissue. This association was observed in 47% of Alzheimer’s patients compared to 25% of unaffected individuals and was confirmed in an independent cohort.

The study, published in Alzheimer’s & Dementia, used tissue samples from the gut, brain, and vagus nerve to uncover biological links between HCMV infection, immune responses, and Alzheimer’s markers like amyloid plaques and tau tangles. The findings suggest that HCMV may influence disease progression through interactions across multiple organ systems.

Laboratory Evidence of HCMV’s Role

Experiments using human cerebral organoids clearly showed that HCMV infection accelerates the production of beta-amyloid 42 and phosphorylated tau-212 which are key markers of Alzheimer’s. Cells that are infected also showed a higher rate of neuronal death which supports the hypothesis that the virus plays an active role in certain Alzheimer’s cases.

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Diagnostic and Therapeutic Implications

The presence of HCMV and IgG4 in tissues, including cerebrospinal fluid, may serve as biomarkers for identifying patients with this Alzheimer’s subtype. Researchers are working on developing a blood test to detect chronic HCMV infections, which could help target antiviral treatments to the most at-risk individuals. These findings may pave the way for new therapeutic strategies aimed at reducing the impact of HCMV in Alzheimer’s disease.

This study represents a step forward in understanding the complex mechanisms behind Alzheimer’s and offers hope for more personalized approaches to its diagnosis and treatment.

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FAQs on Alzheimer’s and the Link to Cytomegalovirus (HCMV)

What is HCMV?
HCMV (human cytomegalovirus) is a common virus that infects most people by adulthood. It usually remains dormant but can reactivate later in life.

How is HCMV linked to Alzheimer’s?
Researchers found that HCMV is associated with a specific subtype of Alzheimer’s, involving CD83(+) immune cells and elevated IgG4 antibodies in the brain, gut, and vagus nerve.

Does everyone with HCMV get Alzheimer’s?
No. While HCMV is common, not all carriers develop Alzheimer’s. Other factors, such as immune responses and genetic predispositions, likely play a role.

What are CD83(+) microglia?
CD83(+) microglia are specialized immune cells in the brain linked to inflammation and Alzheimer’s pathology in certain patients.

What role does the gut play in Alzheimer’s?
The gut may act as a reservoir for HCMV, with the virus potentially traveling to the brain via the vagus nerve, contributing to Alzheimer’s progression.

Can HCMV be treated?
HCMV can be managed with antiviral therapies, but their effectiveness in Alzheimer’s patients is still under investigation.

How might this discovery help patients?
Testing for HCMV and related immune markers (like IgG4) could help identify Alzheimer’s subtypes and guide targeted treatments.

Is this research definitive?
No, but it highlights a strong association that warrants further investigation to confirm the findings and develop treatments.

Can Alzheimer’s be prevented by controlling HCMV?
It’s unclear. Future research will determine if antiviral therapies can reduce Alzheimer’s risk in patients with HCMV.

What’s next for researchers?
They aim to develop diagnostic tests and explore antiviral treatments to address this Alzheimer’s subtype.

Recognized Subtypes of Alzheimer’s Disease and Their Key Characteristics

SubtypeKey FeaturesUnderlying Mechanisms
Early-Onset Alzheimer'sOccurs before the age of 65; accounts for 5-10% of cases.Genetic mutations in APP, PSEN1, or PSEN2 genes; autosomal dominant inheritance.
Late-Onset Alzheimer'sMost common type; occurs after age 65.Associated with age-related factors, APOE ε4 gene, and lifestyle/environmental risks.
Familial Alzheimer'sA rare form with strong genetic inheritance; overlaps with early-onset cases.Mutations in APP, PSEN1, and PSEN2 genes; accounts for less than 1% of cases.
Sporadic Alzheimer'sNo clear genetic cause; the most common type.Likely multifactorial, involving age, lifestyle, environment, and genetic risk (e.g., APOE ε4).
Mixed DementiaCombination of Alzheimer's pathology and other types of dementia, such as vascular dementia.Coexistence of amyloid plaques/tau tangles and vascular damage or Lewy bodies.
HCMV-Associated Alzheimer'sSubtype linked to human cytomegalovirus infection and immune response markers like CD83(+) microglia and IgG4.Cross-tissue interactions involving HCMV in the gut, vagus nerve, and brain.

References

Readhead, B. P., Mastroeni, D. F., Wang, Q., Sierra, M. A., de Ávila, C., Jimoh, T. O., Haure-Mirande, J. V., Atanasoff, K. E., Nolz, J., & others. (2024). Alzheimer’s disease-associated CD83(+) microglia are linked with increased immunoglobulin G4 and human cytomegalovirus in the gut, vagal nerve, and brain. Alzheimer’s & Dementia. https://doi.org/10.1002/alz.14401

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