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

Abstract：

: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.

journal_name

Exp Cell Res

journal_title

Experimental cell research

authors

Eriksdotter M,Navarro-Oviedo M,Mitra S,Wahlberg L,Linderoth B,Tjernberg LO,Behbahani H

doi

10.1016/j.yexcr.2018.08.007

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

175-184

issue

1

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(18)30658-X

journal_volume

371

pub_type

杂志文章

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