Infectious Contributions to Alzheimer's Disease Pathogenesis

Accumulating evidence indicates that microbial agents and immune responses to infection play a substantive role in the onset and progression of Alzheimer’s disease (AD). Neurotropic viruses such as herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) are repeatedly detected in post-mortem brain tissue of affected individuals, often co-localising with hallmark amyloid plaques and neurofibrillary tangles. Bacterial and fungal taxa have likewise been identified in cortical regions, raising the possibility that chronic or latent infections may initiate or exacerbate neuroinflammatory cascades. In parallel, amyloid-β (Aβ) has emerged as an innate immune effector, exhibiting antimicrobial activity against a range of pathogens and suggesting that its deposition may be an early protective response that becomes maladaptive. Systemic immune challenges, including peripheral infections, can breach the blood–brain barrier and activate microglia, promoting sustained cytokine release and synaptic dysfunction. The gut microbiota may further modulate central nervous system immunity, with dysbiosis correlating with altered amyloid processing and tau phosphorylation. Together, these observations support a model whereby repeated or unresolved infections drive chronic neuroinflammation, seeding protein aggregation and neuronal loss. Understanding these interconnected mechanisms holds promise for novel interventions that target microbial triggers, bolster host defences and restore immune equilibrium in the ageing brain.

Research from Nature Portfolio

Recent studies have shown that herpes zoster vaccination is associated with a measurable reduction in subsequent dementia diagnoses. A large natural experiment exploiting birth-date eligibility demonstrated that live-attenuated zoster immunisation reduces the incidence of new dementia cases by approximately 20 percent over seven years, with stronger effects in women. Complementary evidence from the rapid shift to recombinant shingles vaccine use indicates a 17 percent increase in dementia-free survival time post-vaccination, equating to over five months of additional cognitive resilience compared with both live vaccine and other common adult immunisations. These findings reinforce the notion that antiviral immunity can confer off-target neuroprotective benefits and prompt mechanistic investigations into how vaccine-induced immune modulation attenuates neurodegenerative processes. Foundational work also reports the presence of diverse fungal species in multiple brain regions of AD patients but not controls, revealing intracellular and extracellular fungal elements that may contribute to vascular pathology and local inflammation.

Infectious Contributions to Alzheimer's Disease Pathogenesis publication trend

The graph below shows the total number of articles in infectious contributions to alzheimer's disease pathogenesis across all publications each year (not limited to Nature Index journals).

Technical terms

Neurotropic virus: A virus capable of infecting nerve cells and establishing latency in the central nervous system.

Amyloid-β (Aβ): A peptide derived from amyloid precursor protein that aggregates into plaques and exhibits antimicrobial properties.

Microglia: Resident immune cells of the brain that mediate inflammatory responses and phagocytosis.

Blood–brain barrier: A selective endothelial barrier that regulates the passage of cells and molecules between the bloodstream and brain tissue.

Gut–brain axis: Bidirectional communication network linking gastrointestinal microbiota to central nervous system function and immunity.

References

1. A natural experiment on the effect of herpes zoster vaccination on dementia. Nature (2025).
2. The recombinant shingles vaccine is associated with lower risk of dementia. Nature Medicine (2024).
3. Clinical evidence of human pathogens implicated in Alzheimer’s disease pathology and the therapeutic efficacy of antimicrobials: an overview. Translational Neurodegeneration (2023).
4. The Alzheimer's Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide. PLOS ONE (2010).
5. Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice. Journal of Neuroinflammation (2012).
6. 16S rRNA Next Generation Sequencing Analysis Shows Bacteria in Alzheimer’s Post-Mortem Brain. Frontiers in Aging Neuroscience (2017).
7. Different Brain Regions are Infected with Fungi in Alzheimer’s Disease. Scientific Reports (2015).
8. Recurrent herpes simplex virus-1 infection induces hallmarks of neurodegeneration and cognitive deficits in mice. PLOS Pathogens (2019).
9. Corroboration of a Major Role for Herpes Simplex Virus Type 1 in Alzheimer’s Disease. Frontiers in Aging Neuroscience (2018).