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Updated: Oct 13, 2025
Absolute Quantification of Aβ1-42 in CSF Using a Mass Spectrometric Reference Measurement Procedure
Published on: March 21, 2017
Low cerebrospinal fluid Amyloid-βeta 1-42 in patients with tuberculous meningitis
Giacomo Stroffolini1, Giulia Guastamacchia2, Sabrina Audagnotto3
1Amedeo di Savoia Hospital, Infectious Diseases Unit, Department of Medical Sciences, University of Turin, Turin, Italy. giacomo.stroffolini@unito.it.
Background:
Tuberculous meningitis (TBM) is an important disease leading to morbidity, disability and mortality that primarily affects children and immune-depressed patients. Specific neuromarkers predicting outcomes, severity and inflammatory response are still lacking. In recent years an increasing number of evidences show a possible role for infective agents in developing neurodegenerative diseases.
Methods:
We retrospectively included 13 HIV-negative patients presenting with TBM and we compared them with two control groups: one of patients with a confirmed diagnosis of AD, and one of those with syphilis where lumbar punctures excluded central nervous system involvement. Lumbar punctures were performed for clinical reasons and CSF biomarkers were routinely available: we analyzed blood brain barrier permeability (CSF to serum albumin ratio, "CSAR"), intrathecal IgG synthesis, (CSF to serum IgG ratio), inflammation (neopterin), amyloid deposition (Aβ1-42), neuronal damage (T-tau, P-tau, 14.3.3) and astrocytosis (S-100 β).
Results:
TBM patients were 83 % male and 67 % Caucasian with a median age of 51 years (24.5-63.5 IQR). Apart from altered CSAR (median value 18.4, 17.1-30.9 IQR), neopterin (14.3 ng/ml, 9.7-18.8) and IgG ratios (15.4, 7.9-24.9), patients showed very low levels of Aβ1-42 in their CSF (348.5 pg/mL,125-532.2), even lower compared to AD and controls [603 pg/mL (IQR 528-797) and 978 (IQR 789-1178)]. Protein 14.3.3 tested altered in 38.5 % cases. T-tau, P-tau and S100Beta were in the range of normality. Altered low level of Aβ1-42 correlated over time with classical TBM findings and altered neuromarkers.
Conclusions:
CSF Biomarkers from patients with TBM were compatible with inflammation, blood brain barrier damage and impairment in amyloid-beta metabolism. Amyloid-beta could be tested as a prognostic markers, backing the routine use of available neuromarkers. To our knowledge this is the first case showing such low levels of Aβ1-42 in TBM; its accumulation, drove by neuroinflammation related to infections, can be central in understanding neurodegenerative diseases.
Insights
Tuberculous meningitis (TBM) is linked to low amyloid-beta levels in cerebrospinal fluid, suggesting a role in neuroinflammation and potential prognostic value. These findings highlight new avenues for understanding neurodegenerative diseases.
Area of Science:
- Neurology
- Infectious Diseases
- Biomarker Research
Background:
- Tuberculous meningitis (TBM) causes significant morbidity and mortality, particularly in children and immunocompromised individuals.
- Current diagnostic and prognostic tools for TBM lack specific neuromarkers for outcomes and inflammatory responses.
- Emerging evidence suggests a link between infections and neurodegenerative diseases.
Purpose of the Study:
- To investigate cerebrospinal fluid (CSF) biomarkers in patients with TBM.
- To compare TBM patients with Alzheimer's disease (AD) and syphilis patients.
- To identify potential prognostic markers for TBM and neurodegenerative processes.
Main Methods:
- Retrospective analysis of 13 HIV-negative TBM patients.
- Comparison with control groups diagnosed with AD and syphilis (neurologically unaffected).
- Analysis of CSF biomarkers including albumin ratio (CSAR), IgG synthesis, neopterin, Aβ1-42, T-tau, P-tau, 14.3.3, and S-100 β.
Main Results:
- TBM patients exhibited altered CSAR, neopterin, and IgG ratios.
- Significantly lower levels of CSF amyloid-beta 1-42 (Aβ1-42) were observed in TBM patients compared to AD and control groups.
- Altered Aβ1-42 levels correlated with TBM progression and other CSF inflammatory markers.
Conclusions:
- CSF biomarker profiles in TBM indicate inflammation, blood-brain barrier damage, and impaired amyloid-beta metabolism.
- Low Aβ1-42 levels in TBM may serve as a prognostic marker, supporting the use of routine neuromarkers.
- This study is the first to report such low Aβ1-42 in TBM, suggesting neuroinflammation's role in neurodegeneration.
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