Stimulation of endogenous neurogenesis by anti-EFRH immunization in a transgenic mouse model of Alzheimer's disease.
Neurogenesis is a subject of intense interest and extensive research, but it stands at the center of a bitter debate over ethical and practical problems. Neurodegenerative diseases, such as Alzheimer's disease (AD), accompanied by a shifting balance between neurogenesis and neurodegeneration, are suitable for stimulation of neurogenesis for the benefit of diseased patients. We have previously shown that Abs against the EFRH sequence of beta-amyloid peptide (AbetaP) prevent aggregation and disaggregate AbetaP both in vitro and in vivo. EFRH, located in the soluble tail of the N-terminal region, acts as a regulatory site controlling both solubilization and disaggregation processes in the AbetaP molecule. Here we show that anti-EFRH immunotherapy of a platelet-derived amyloid precursor protein transgenic mouse model of AD stimulates endogenous neurogenesis, suggested by elevated numbers of BrdU-incorporated cells, most of which are colocalized with a marker of mature neurons, NeuN. These newly born neurons expressed the activity-dependent gene Zif268, indicating their functional integration and participation in response to synaptic input in the brain. These findings suggest that anti-amyloid immunotherapy may promote recovery from AD or other diseases related to AbetaP overproduction and neurotoxicity by restoring neuronal population, as well as cognitive functions in treated patients.
Becker
Maria
M
Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat Aviv, Tel-Aviv 69978, Israel.
Lavie
Vered
V
Solomon
Beka
B
D000544:Alzheimer Disease / Q000235:genetics* / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000473:pathology; D001973:Bromodeoxyuridine / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000628:therapy*; D009474:Neurons / Q000378:metabolism*; D010641:Phenotype
D016229:Amyloid beta-Peptides; D001973:Bromodeoxyuridine