βCTF-Correlated Burst of Hippocampal TNFα Occurs at a Very Early, Pre-Plaque Stage in the TgCRND8 Mouse Model of Alzheimer's Disease

Article type: Short Communication

Authors: Cavanagh, Chelsea^{; 1} | Colby-Milley, Jessica^{; 1} | Bouvier, David | Farso, Mark | Chabot, Jean-Guy | Quirion, Rémi | Krantic, Slavica^{; *}

Affiliations: Douglas Mental Health University Institute (DMHUI), Department of Psychiatry, McGill University, Verdun (Montréal), QC, Canada

Correspondence: [*] Correspondence to: Slavica Krantic, PhD, Centre de Recherche des Cordeliers, UMRS 872, équipe 19, 15, rue de l'école de medicine, 75 000 Paris, France. Tel.: +33 144 279 037; Fax: +33 144 279 036; E-mail: [email protected].

Note: [1] These authors contributed equally to this manuscript.

Abstract: Tumor necrosis factor-alpha (TNFα) regulates neuronal excitability. We investigated whether alterations in the level of TNFα occur at a time point that precedes the reported seizure-associated hyperexcitability of hippocampal networks in pre-plaque models of Alzheimer's disease (AD). Western blot and ELISA experiments indicated a significant increase in hippocampal TNFα expression in 1-month-old TgCRND8 mice that correlated with levels of the β-C-terminal fragment (βCTF) of amyloid-β protein precursor. CD11b labeling indicated changes in microglial morphology toward an activated state, suggesting that these cells may be a putative source of the observed TNFα increase during this pre-symptomatic stage of AD-like pathology.

Keywords: Alzheimer's disease, β-C-terminal fragment, pre-plaque, TgCRND8 mice, tumor necrosis factor-α

DOI: 10.3233/JAD-122131

Journal: Journal of Alzheimer's Disease, vol. 36, no. 2, pp. 233-238, 2013