Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 31, Issue 3, Pages 651-657Publisher
IOS PRESS
DOI: 10.3233/JAD-2012-120856
Keywords
Amyloid-beta; co-cultures; computer-assisted analysis; Definiens Cognition Network Technology; LPS; microglia; neuronal injury; neuronal viability; Toll-like receptor; Pam(3)CSK(4)
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Funding
- Robert Bosch Foundation, Stuttgart, Germany (Forschungskolleg Geriatrie)
- Heidenteich von Siebold - Programm at the University of Gottingen, Germany
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Activated microglia is considered to be involved in the progression of Alzheimer's disease (AD). We investigated the effect of amyloid-beta(1-40) (A beta(40)) and exogenous agonists of Toll-like receptor (TLR) 1/2 (Pam(3)CSK(4)) and TLR4 (LPS) on neurons in primary murine neuron-microglia co-cultures. Neuronal viability, assessed by quantifying the number of intact neuronal extensions and their crossings using a newly developed Definiens Cognition Network Technology-based method, was significantly decreased after treatment with Pam(3)CSK(4), LPS, and A beta(40). Combined treatment with A beta(40) and Pam(3)CSK(4) or LPS had an additive effect. Hence, in patients with AD, synergistic microglial activation by A beta and bacterial products during infections might contribute to disease progression.
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