MICROBES AS A SOURCE OF NEURO-INFLAMMATION IN ALZHEIMER’S DISEASE: A PILOT ANALYSIS OF BACTERIAL LOAD, AΒ40, AND VIMENTIN IN TEMPORAL CORTEX AND CHOROID PLEXUS
Main Article Content
Keywords
Alzheimer’s disease; choroid plexus; temporal cortex; bacteria; amyloid-β40; vimentin; neuro-inflammation.
Abstract
Background: Alzheimer’s disease (AD) is increasingly linked to chronic neuro-inflammation, but the triggers that initiate and sustain this response remain elusive. Mounting evidence shows bacterial DNA and viable pathogens in AD brains, with vascular‐adjacent structures such as the choroid plexus (CP) posited as portals of entry. We explored total bacterial burden, amyloid-β40 (Aβ40) concentration and vimentin dynamics in matched temporal cortex (TC) and CP from AD and control brains.
Methods: Frozen TC (Brodmann area 21) and CP samples from the South-West Dementia Brain Bank (6 controls, 7 AD) were processed under sterile conditions. Total DNA was extracted, quantified by β-globin qPCR, and assayed for bacterial 16S rRNA gene copies with contamination-minimised reagents. Aβ40 in guanidine-solubilised pellets was measured by sandwich ELISA; soluble vimentin and phospho-Ser56-vimentin were assessed by Western blot. Statistics included Welch’s t-tests, two-way ANOVA and Pearson correlation.
Results: Mean log10 bacterial copies per 50 ng DNA were significantly higher in TC of AD cases (5.29 ± 0.53) than controls (4.49 ± 0.37; p=0.014); no difference emerged in CP. Two-way ANOVA showed a strong tissue effect (TC > CP, p=0.008) without group–tissue interaction. Aβ40 concentrations trended higher in AD TC (32 044 pg µL⁻¹) versus controls (10 424 pg µL⁻¹, p=0.098). Vimentin immunoblots revealed greater total and phospho-vimentin in AD, especially in CP. Bacterial load did not correlate with Aβ40 (r = 0.13, NS).
Conclusion: TC harbours a markedly elevated bacterial burden in AD, supporting the hypothesis that microbes contribute to regional neuro-inflammation. CP shows abundant vimentin but modest bacterial DNA, suggesting barrier activation rather than colonisation. Larger cohorts and species-specific assays are warranted to delineate causal links.
References
2. Emery DC, Shoemark DK, Batstone TE, Waterfall CM, Coghill JA, Cerajewska TL, et al. 16S rRNA next-generation sequencing analysis shows bacteria in Alzheimer’s post-mortem brain. Front Aging Neurosci. 2017;9:195.
3. Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman BT, et al. The Alzheimer’s disease-associated amyloid-β protein is an antimicrobial peptide. PLoS One. 2010;5(3):e9505.
4. Balin BJ, Gerard HC, Arking EJ, Appelt DM, Branigan PJ, Abrams JT, et al. Identification and localization of Chlamydia pneumoniae in the Alzheimer brain. Med Microbiol Immunol. 1998;187(1):23-42.
5. Mak TN, Brüggemann H. Vimentin in Bacterial Infections. Cells. 2016 Apr 18;5(2):18. doi: 10.3390/cells5020018. PMID: 27096872; PMCID: PMC4931667.
6. Johanson CE, Stopa EG, McMillan PN. The aging choroid plexus and blood-CSF barrier: implications for neurodegenerative disease. J Neurol. 2022;269(9):4782-4796.
7. Canobbio I, Abubaker AA, Visconte C, Torti M, Pula G. Role of amyloid peptides in vascular dysfunction and platelet dysregulation in Alzheimer's disease. Front Cell Neurosci. 2015 Mar 3;9:65. doi: 10.3389/fncel.2015.00065. PMID: 25784858; PMCID: PMC4347625.
8. Sansores-España LD, Melgar-Rodríguez S, Olivares-Sagredo K, Cafferata EA, Martínez-Aguilar VM, Vernal R, Paula-Lima AC, Díaz-Zúñiga J. Oral-Gut-Brain Axis in Experimental Models of Periodontitis: Associating Gut Dysbiosis With Neurodegenerative Diseases. Front Aging. 2021 Dec 10;2:781582. doi: 10.3389/fragi.2021.781582. PMID: 35822001; PMCID: PMC9261337.
9. Zhan X, Stamova B, Jin LW, DeCarli C, Phinney B, Sharp FR. Gram-negative bacterial molecules associate with Alzheimer’s disease pathology. Neurology. 2016;87(22):2324-32.
10. Pisa D, Alonso R, Rábano A, Rodal I, Carrasco L. Different brain regions are infected with fungi in Alzheimer’s disease. Sci Rep. 2015;5:15015.
11. Miklossy J. Alzheimer’s disease – a neurospirochetosis. Analysis of the evidence following Koch’s and Hill’s criteria. J Neuroinflammation. 2011;8:90.
12. Loeb MB, Molloy DW, Smieja M, Standish T, Goldsmith CH, Mahony J, et al. A randomized, controlled trial of doxycycline and rifampin for Alzheimer’s disease. Neurology. 2004;63(1):65-71.
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All articles published in JPTCP are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.
Dr Akshara Jogi
Consultant Pathologist, MMF's Joshi & Ratna Memorial Hospitals, Pune