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Low cerebrospinal fluid beta-amyloid 42 in patients with acute bacterial meningitis and normalization after treatment
M Sjögren1, M Gisslén, E Vanmechelen
1Institute of Clinical Neuroscience, Göteborg University, Sahlgrenska University Hospital, Mölndal, SE 431 80 Mölndal, Sweden. magnus.sjogren@medfak.gu.se
Abstract:
CSF-A beta 42 may be a marker of Alzheimer's disease (AD). A decreased level of CSF-A beta 42 is consistently found in AD and has been suggested to be related to the deposition of amyloid plaques in the brain. However, low CSF-A beta 42 levels have also been found in disorders devoid of plaques, for instance Creutzfeldt-Jakob disease. To examine if the level of A beta 42 in CSF is related to inflammatory processes, we studied CSF-A beta 42 levels in eight patients with acute purulent bacterial meningitis, 10 patients with acute viral meningitis and 18 age-matched controls. In acute purulent bacterial meningitis, the CSF-A beta 42 level was markedly reduced (28% of that in controls, P<0.0001), whereas no change was found in viral meningitis. After successful treatment of bacterial meningitis, the CSF-A beta 42 level increased (P<0.05 compared to baseline) and did no longer differ from that in controls (ns). The decrease could not be explained by interference with high protein levels, since addition of increasing volumes of serum did not influence the CSF-A beta 42 levels. Our findings suggest that the reduction in CSF-A beta 42 found in bacterial meningitis is not a direct consequence of the inflammatory process. The cause may be disturbance of the clearance of A beta 42 from the brain.
Insights
Cerebrospinal fluid (CSF) amyloid-beta 42 (A beta 42) levels decrease significantly in bacterial meningitis, not due to inflammation but possibly impaired clearance. Levels normalize after treatment, suggesting a reversible process distinct from Alzheimer's disease pathology.
Area of Science:
- Neurology
- Biochemistry
- Infectious Diseases
Background:
- Cerebrospinal fluid (CSF) amyloid-beta 42 (A beta 42) is a potential Alzheimer's disease (AD) biomarker, with decreased levels linked to amyloid plaque deposition.
- Low CSF A beta 42 is also observed in non-AD conditions like Creutzfeldt-Jakob disease, suggesting other factors influence its levels.
Purpose of the Study:
- To investigate the relationship between CSF A beta 42 levels and inflammatory processes, specifically in acute meningitis.
- To determine if bacterial meningitis affects CSF A beta 42 levels and if this is related to inflammation or clearance mechanisms.
Main Methods:
- Measured CSF A beta 42 levels in patients with acute purulent bacterial meningitis, acute viral meningitis, and age-matched controls.
- Assessed changes in CSF A beta 42 levels after successful treatment of bacterial meningitis.
- Investigated potential interference of high protein levels on CSF A beta 42 measurements.
Main Results:
- Marked reduction (28%) in CSF A beta 42 levels observed in bacterial meningitis (P<0.0001), with no change in viral meningitis.
- CSF A beta 42 levels increased significantly after treatment for bacterial meningitis (P<0.05) and normalized compared to controls.
- High protein levels in CSF did not interfere with the measurement of CSF A beta 42.
Conclusions:
- The reduction in CSF A beta 42 during bacterial meningitis is unlikely a direct result of the inflammatory process itself.
- The findings suggest that bacterial meningitis may disrupt the clearance of A beta 42 from the brain, leading to decreased CSF levels.
- This CSF A beta 42 reduction in meningitis is distinct from the pathology seen in Alzheimer's disease.