Exploring the role of multi-pathogen infections in Alzheimer's disease: A case-control study

Alzheimer's disease (AD) is a leading cause of dementia. Following the discovery of the amyloid's antimicrobial properties, research has focused on infectious agents as potential contributors. This study investigates the role of multi-pathogen infections in AD by analyzing serological and molecular microbiologic markers in serum and cerebrospinal fluid (CSF).

A unicentric case-control study was conducted in AD patients (n=44) and healthy controls (n=35) in a Spanish reference cognitive disorders unit. Serum and CSF samples were analyzed using chemiluminescence immunoassay and ELISA for several pathogens. Molecular detection was performed through nucleic acid amplification. Multivariable logistic regression with bootstrap validation identified independent predictors of AD.

Seropositivity for HCMV and Coxiella burnetii was significantly more frequent in AD patients, with C. burnetii linked to rapid progression. No microbial DNA was detected in CSF. Age (OR 1.55, 95% CI 1.17-2.03), HCMV (OR 20.02, 95% CI 2.64-183.38), and Chlamydia pneumoniae (OR 8.60, 95% CI 0.96-96.57) seropositivity were independent predictors of AD in the adjusted logit model, with an AUC of 0.79 after bootstrap validation. Wide confidence intervals indicate uncertainty in the exact strength of association. Triple-positive patients (HCMV, C. pneumoniae, C. burnetii) showed faster progression, poorer neuropsychological performance, and impaired CSF biomarkers, including lower A40/A42 ratios and higher neurofilament light levels.

Latent infections with HCMV, C. pneumoniae, and C. burnetii may contribute to AD pathophysiology, possibly through systemic or immune-mediated mechanisms. Further studies are needed to replicate these findings and clarify the role of infectious burden in AD.