The pertussis hypothesis: Bordetella pertussis colonization in the pathogenesis of Alzheimer's disease.
Immunobiology
; 222(2): 228-240, 2017 02.
Article
em En
| MEDLINE
| ID: mdl-27692981
ABSTRACT
While a number of endogenous risk factors including age and genetics are established for Alzheimer's disease (AD), identification of acquired, potentially preventable or treatable causes, remains limited. In this paper, we review three epidemiologic case studies and present extensive biologic, immunologic and anatomic evidence to support a novel hypothesis that Bordetella pertussis (BP), the bacterium better known to cause whooping cough, is an important potential cause of AD. Cross-cultural documentation of nasopharyngeal subclinical BP colonization reflecting BP-specific mucosal immunodeficiency, proximate anatomy of intranasal mucosal surfaces to central nervous system (CNS) olfactory pathways, and mechanisms by which BP and BP toxin account for all hallmark pathology of AD are reviewed, substantiating biologic plausibility. Notably, respiratory BP infection and BP toxin secreted from subclinical BP colonization can account for the initiation and accumulation of amyloid ß plaques and tau tangles. Additional mechanisms consistent with the immunobiologic effects of subclinical BP colonization include microglial activation and inflammation, atrophy and neurodegeneration, excitotoxicity, distinctive anatomic distribution and sequential spread of disease, impaired glucose utilization, and other characteristic CNS pathology of AD. We conclude by assessing the evidence for causation against the Bradford Hill criteria, and advocate for further investigation into the potential role of BP in the etiology of AD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bordetella pertussis
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Coqueluche
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Doença de Alzheimer
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Incidence_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Immunobiology
Ano de publicação:
2017
Tipo de documento:
Article