Active A beta vaccination fails to enhance amyloid clearance in a mouse model of Alzheimer%26apos;s disease with A beta 42-driven pathology

作者：Nemirovsky Anna; Shapiro Jenny; Baron Rona; Kompaniets Alex; Monsonego Alon^*

来源：Journal of Neuroimmunology, 2012, 247(1-2): 95-99.

DOI：10.1016/j.jneuroim.2012.03.017

• Alzheimer%26apos
• s disease
• Amyloid beta-peptide
• Vaccine
• A beta antibodies

A beta vaccination has been shown to induce remarkable clearance of brain amyloid plaques in mouse models of Alzheimer%26apos;s disease (AD). However, the extent to which antibody-mediated A beta clearance is affected by predominant formation of A beta 42 over A beta 40 is unclear. Here we demonstrate for the first time that in a mouse model carrying the human APP mutations KM670/671NL and the human PS1 mutation P166L, A beta vaccination does not result in plaque clearance. This was in spite of the strong T- and B-cell immune responses evoked under the DR1501 genetic background and the activation of microglia at sites of A beta plaques. Our findings suggest the existence of antibody-resistant forms of A beta deposits in the brain consisting of primarily A beta 42, and shed light on the mechanisms of antibody-dependent amyloid clearance as well as novel therapeutic strategies for AD.

• 出版日期2012-6-15