Affiliations: Department of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA, USA
Correspondence:
[*]
Correspondence to: Dr. Nicholas H. Varvel and Dr. Thota Ganesh, Department of Pharmacology and Chemical
Biology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA. Tel.: +1 404 727 7393;
Fax: +1 404 727 5635; E-mails: nvarvel@emory.edu (N.H. Varvel) and tganesh@emory.edu (T. Ganesh)
Abstract: Alzheimer’s disease (AD) pathology consists of extracellular deposits of amyloid-β peptides (Aβ) and intracellular neurofibrillary tangles. These pathological alterations are accompanied by a neuroinflammatory response consisting of increased expression of inflammatory mediators. An anti-inflammatory strategy designed to prevent or delay the development of AD would benefit from knowing when neuroinflammation appears in the transgenic models during prodromal disease stages relative to Aβ pathology. We investigated the expression patterns of inflammatory mediators in the brain of 5xFAD mice in comparison to development of Aβ deposition. Expression changes in inflammatory mediators and glial markers are more robust in female mice starting at three months of age, in contrast to males in which there is no clear trend through five months. Female and male 5xFAD mice also displayed an age-dependent increase in cortical Aβ deposition congruent with neuroinflammation. Thus, in the 5xFAD mouse model of AD, administration of an anti-inflammatory agent would be most efficacious when administered before three months of age.
