Evidence map›Paper›PMID 40584180›Full record

ReviewFrontiers in aging neuroscience2025

Infections with

Alexa Romanella, Maegan McCall, Rachel Corwin, Alaha Abdul Faruq, Emily Lingo, Sanya Bhambhani, Christine J Hammond, Brian J Balin

Abstract readReview
In one paragraph

Review in Frontiers in aging neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
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

8 authors.

Alexa RomanellaDepartment of Bio-Medical Sciences, Center for Chronic Disorders of Aging, Philadelphia College of Osteopathic Medicine (PCOM), Philadelphia, PA, United States.
Maegan McCallDivision of Research, Center for Chronic Disorders of Aging, Philadelphia College of Osteopathic Medicine (PCOM), Philadelphia, PA, United States.
Rachel CorwinDepartment of Bio-Medical Sciences, Center for Chronic Disorders of Aging, Philadelphia College of Osteopathic Medicine (PCOM), Philadelphia, PA, United States.
Alaha Abdul FaruqDepartment of Bio-Medical Sciences, Center for Chronic Disorders of Aging, Philadelphia College of Osteopathic Medicine (PCOM), Philadelphia, PA, United States.
Emily LingoDepartment of Bio-Medical Sciences, Center for Chronic Disorders of Aging, Philadelphia College of Osteopathic Medicine (PCOM), Philadelphia, PA, United States.
Sanya BhambhaniDepartment of Bio-Medical Sciences, Center for Chronic Disorders of Aging, Philadelphia College of Osteopathic Medicine (PCOM), Philadelphia, PA, United States.
Christine J HammondDivision of Research, Center for Chronic Disorders of Aging, Alzheimer's Pathobiome Initiative, Philadelphia College of Osteopathic Medicine (PCOM), Philadelphia, PA, United States.
Brian J BalinDepartment of Bio-Medical Sciences, Center for Chronic Disorders of Aging, Alzheimer's Pathobiome Initiative, Philadelphia College of Osteopathic Medicine (PCOM), Philadelphia, PA, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the world, but our understanding of causation is still lacking. A current evidence-based hypothesis proposes that certain infectious agents initiate the neurodegeneration consistent with AD. Two infectious agents correlated to AD pathogenesis are Methods: This review focused on peer-reviewed original research and review articles evaluating the potential association of Cpn and SARS-CoV-2 with AD. Our focus included: genetic risk with expression of APOEε4 and other biomarkers common to AD including interleukin-6 (IL-6), chemokine ligand 2 (CCL2), neuropilin-1 (NRP1), and structural/functional aspects of the infectious processes and resultant neuroinflammation. Results: Both Cpn and SARS-CoV-2 may infect the neuroepithelium of the olfactory system to enter the brain. Cpn binds to heparan sulfate proteoglycans for entry into mucosal cells. SARS-CoV-2 infects epithelia after binding to ACE2 receptors. Once inside the neuroepithelium, the pathogens may traffic to the olfactory bulbs. NRP1, an abundant receptor in AD, also potentiates SARS-CoV-2 infection. Furthermore, both pathogens may enter the systemic circulation for eventual entry through the blood brain barrier. The SARS-CoV-2 spike protein, in conjunction with CCL2, co-stimulates macrophages, resulting in IL-6 cytokine release. Likewise, Cpn infection leads to an increase of CCL2 and IL-6 cytokine release. The primary infection of either organism may lead to chronically elevated levels of IL-6 and secondary infection(s). Additionally, host APOEε4 expression appears to increase susceptibility to Cpn and SARS-CoV-2 infections. Discussion: Cpn and SARS-CoV-2 may enter the brain through olfactory neuroepithelial cells and/or through the blood brain barrier. SARS-CoV-2 utilizes specific receptors for infection, while Cpn utilizes binding of proteoglycans. Neuroinflammation may be an outcome of infection with one or both organisms as observed by increased levels of CCL2 and IL-6 leading to AD pathogenesis. Genetic risk is noted for infection with both organisms with expression of APOEε4. Ongoing and future studies will further dissect mechanisms of infection with SARS-CoV-2 and Cpn as they may inform on causation and diagnostic factors for AD.

Indexed as

Alzheimer’s diseaseblood-brain barrierChlamydia pneumoniaeneuroinflammationolfactionSARS-CoV-2

Identifiers

PMID40584180
PMCPMC12202369

What OpenQuestion holds

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LicenceCC BY
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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.