Toll-Like Receptor 2 Acts as a Natural Innate Immune Receptor to Clear Amyloid β1–42and Delay the Cognitive Decline in a Mouse Model of Alzheimer's Disease

• DOI: 10.1523/jneurosci.1146-08.2008
• Publication Date: 2008-05-28T18:08:09Z
• Authors: Karine L. Richard; Mohammed Filali; Paul Préfontaine; Serge Rivest
• Keywords: 0301 basic medicine; Analysis of Variance; Amyloid beta-Peptides; Behavior, Animal; Age Factors; Mice, Transgenic; Plaque, Amyloid; Hippocampus; Receptors, N-Methyl-D-Aspartate; Peptide Fragments; 3. Good health; Amyloid beta-Protein Precursor; Disease Models, Animal; Mice; 03 medical and health sciences; Gene Expression Regulation; Alzheimer Disease; Avoidance Learning; Presenilin-1; Reaction Time; Animals; Humans; Cognition Disorders

Microglia are the immune cells of brain, they activated in brain Alzheimer's disease (AD) patients and mouse models AD, express innate receptor toll-like 2 (TLR2). The present study investigated role this progression AD-like pathologies. Here we show that amyloid β (Aβ) stimulates TLR2 expression a small proportion microglia. We then generated triple transgenic mice deficient from harbor mutant human presenelin 1 chimeric mouse/human precursor protein (APP) genes. deficiency accelerated spatial contextual memory impairments, which correlated with increased levels Aβ 1–42 transforming growth factor β1 brain. NMDA receptors 2A were also lower hippocampus APP–TLR2 −/− mice. Gene therapy bone marrow using lentivirus constructs expressing rescued cognitive impairment Indeed, lenti-green fluorescent protein/TLR2 treatment had beneficial effects by restoring consolidation process disrupted APP These data suggest acts as an endogenous for clearance toxic bone-marrow-derived cells. decline is markedly context deficiency. Upregulating may be considered potential new powerful therapeutic approach AD.