Cerebrospinal fluid from Alzheimer patients affects cell-mediated nerve growth factor production and cell survival in vitro

Exp Cell Res. 2018 Oct 1;371(1):175-184. doi: 10.1016/j.yexcr.2018.08.007. Epub 2018 Aug 6.


Alzheimer's disease (AD) is characterized by early degeneration of cholinergic neurons and decreased levels of nerve growth factor (NGF). Thus, increasing the NGF levels by for instance encapsulated cell bio-delivery (ECB) is a potential treatment strategy. The results from our previous first-in-human studies on ECB of NGF to the basal forebrain cholinergic neurons were promising, but indicated some variability of long-term viability of the encapsulated cells and associated reduced NGF-release. Here we studied the effect of amyloid beta-peptides (Aβ), interleukin 1-beta (IL-1β), and CSF from AD, Lewy body dementia (LBD) or subjective cognitive impairment (SCI) patients on the NGF overproducing cell line NGC-0295. At physiological concentrations, neither Aβ40 nor Aβ42 had any major impact on cell viability or NGF-production. In contrast, IL-1β dose-dependently affected NGF-production over time. Exposure of NGF-producing cells to CSF from AD patients showed significantly reduced NGF-release as compared to CSF from LBD or SCI patients. By mass spectrometry we found 3 proteins involved in inflammatory pathways to have an altered expression in AD CSF compared to LBD and SCI. Cell survival and NGF-release were not affected by Aβ. NGF-release was affected by IL-1β, suggesting that inflammation has a negative effect on ECB cells.

Keywords: AD; Amyloid beta (Aβ); CSF; ECB; IL-1β; NGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / pharmacology
  • Cell Line, Transformed
  • Cell Survival / drug effects
  • Cerebrospinal Fluid / chemistry*
  • Cognitive Dysfunction / cerebrospinal fluid
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / pathology
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Gene Expression Regulation / drug effects*
  • Humans
  • Interleukin-1beta / pharmacology*
  • Lewy Body Disease / cerebrospinal fluid
  • Lewy Body Disease / genetics
  • Lewy Body Disease / pathology
  • Nerve Growth Factor / genetics*
  • Nerve Growth Factor / metabolism
  • Peptide Fragments / pharmacology
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / metabolism
  • Staurosporine / pharmacology


  • Amyloid beta-Peptides
  • IL1B protein, human
  • Interleukin-1beta
  • NGF protein, human
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • Nerve Growth Factor
  • Staurosporine