Low cerebrospinal fluid Amyloid-βeta 1–42 in patients with tuberculous meningitis

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.