Cerebrospinal fluids from Alzheimer's disease patients exhibit neurotoxic effects on neuronal cell cultures

Abstract

A growing number of studies suggest amyloid‐β and tau present in cerebrospinal fluid (CSF) and blood as putative biomarkers for Alzheimer's disease (AD). However, there is a question whether these compounds present in patients' bodily fluids can directly cause neurotoxic effects. We investigated effects of AD and other dementia (OD) patients' blood serum and CSF on viability of cells in primary cerebellar granule cell cultures. Overall 59 individuals participated in the study of which 55 samples of biological fluids were taken. Participants were classified into early (E‐AD) and middle (M‐AD) stages of AD, cognitively healthy control (HC) and OD groups. We found that concentrations of total and phosphorylated tau were higher in CSF from AD patients while amyloid‐β₄₂ and amyloid‐β₄₀ in serum was lowered compared to HC. The most cytotoxic effects were induced by CSFs from M‐AD patients which caused neuronal necrosis and suppressed microglial proliferation whereas CSFs from groups of other patients did not kill neurons. Serum and CSF from E‐AD group caused reduction of neuronal numbers in cultures. There were no significant differences in levels of CSF biomarkers between AD groups although both tau species in CSFs from M‐AD patients were found to be significantly elevated compared to HC. Our data suggest that biological fluids from E‐AD induce neuronal loss whereas effects of CSF on reduction in neuronal viability can serve as an indicator of M‐AD and may be associated with extracellular tau.

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