Evidence map›Paper›PMID 26401998›Full record

ReviewJournal of Alzheimer's disease : JAD2015

Herpes Simplex Virus Type 1 and Other Pathogens are Key Causative Factors in Sporadic Alzheimer's Disease.

Steven A Harris, Elizabeth A Harris

Open access · hybridAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Journal of Alzheimer's disease : JAD, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
128citing papers in PubMed, 2 pooled it
13.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

128 citing papers in PubMed, 2 syntheses or guidelines pooled it, 278 citations in OpenAlex.

  1. Pooled it
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  9. Exploring the role of infectious pathogens in Alzheimer's disease neuroinflammation.Frontiers in cellular and infection microbiology · 2026
    Review
  10. The association of common infectious exposures with cognitive performance in community-dwelling older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  11. Physics of Protein Aggregation in Normal and Accelerated Brain Aging.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
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68 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 2 institutions in 1 country.

Steven A HarrisSt. Vincent Medical Group, Northside Internal Medicine, Indianapolis, IN, USA.
Elizabeth A HarrisIndiana University School of Medicine, Indianapolis, IN, USA.
Indiana University – Purdue University Indianapolis · USSt. Vincent Hospital · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This review focuses on research in epidemiology, neuropathology, molecular biology, and genetics regarding the hypothesis that pathogens interact with susceptibility genes and are causative in sporadic Alzheimer's disease (AD). Sporadic AD is a complex multifactorial neurodegenerative disease with evidence indicating coexisting multi-pathogen and inflammatory etiologies. There are significant associations between AD and various pathogens, including Herpes simplex virus type 1 (HSV-1), Cytomegalovirus, and other Herpesviridae, Chlamydophila pneumoniae, spirochetes, Helicobacter pylori, and various periodontal pathogens. These pathogens are able to evade destruction by the host immune system, leading to persistent infection. Bacterial and viral DNA and RNA and bacterial ligands increase the expression of pro-inflammatory molecules and activate the innate and adaptive immune systems. Evidence demonstrates that pathogens directly and indirectly induce AD pathology, including amyloid-β (Aβ) accumulation, phosphorylation of tau protein, neuronal injury, and apoptosis. Chronic brain infection with HSV-1, Chlamydophila pneumoniae, and spirochetes results in complex processes that interact to cause a vicious cycle of uncontrolled neuroinflammation and neurodegeneration. Infections such as Cytomegalovirus, Helicobacter pylori, and periodontal pathogens induce production of systemic pro-inflammatory cytokines that may cross the blood-brain barrier to promote neurodegeneration. Pathogen-induced inflammation and central nervous system accumulation of Aβ damages the blood-brain barrier, which contributes to the pathophysiology of AD. Apolipoprotein E4 (ApoE4) enhances brain infiltration by pathogens including HSV-1 and Chlamydophila pneumoniae. ApoE4 is also associated with an increased pro-inflammatory response by the immune system. Potential antimicrobial treatments for AD are discussed, including the rationale for antiviral and antibiotic clinical trials.

Indexed as

Herpesvirus 1, HumanAlzheimer DiseaseAnimalsBrainHerpes SimplexHumansAlzheimer’s diseaseamyloidApoE4CytomegalovirusdementiaHerpes simplexneurodegenerationpathogen

Identifiers

PMID26401998
PMCPMC4923765
OpenAlexW2213335032

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.