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

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 from whom 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 the serum was lower 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 the groups of other patients did not kill neurons. Serum and CSF from the E‐AD group caused a reduction of neuronal numbers in cultures. There were no significant differences in levels of CSF biomarkers between the 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 the reduction in neuronal viability can serve as an indicator of M‐AD and may be associated with extracellular tau. The study data demonstrate that in cerebellar granule cell cultures: (i) biological fluids from early stages Alzheimer's disease patients induce rapid neuronal loss and (ii) cerebrospinal fluids from middle stages Alzheimer's disease patients induce neuronal necrosis and inhibit microglial proliferation. Such effects are not seen in cell cultures exposed to bodily fluids from cognitively healthy or other types of dementia patients.