Passive (amyloid-β) immunotherapy attenuates monoaminergic axonal degeneration in the AβPPswe/PS1dE9 mice.
The role of amyloid-β (Aβ in the neurodegeneration of Alzheimer's disease remains controversial, to a large extent because of the lack of robust neurodegeneration in mouse models of AD. To address this question, we examined the effects of Aβ antibodies in the recently described monoaminergic (MAergic) axonal degeneration in AβPPswe/PS1dE9 mice. To determine if Aβ accumulation is directly involved in degeneration of MAergic axons, we examined the effects of passive anti-Aβ antibody (7B6) administration on Aβ pathology and MAergic degeneration in AβPPswe/PS1dE9 mice. Injections of monoclonal antibody (mAb) 7B6 into mice (6 to 9 months of age) resulted in a modest reduction of Aβ load in the brains of AβPPswe/PS1dE9 mice. In addition, 7B6 treated AβPPswe/PS1dE9 mice had significantly higher densities of MAergic axons in both cortex and in hippocampus as compared to untreated mutant mice. For example, 7B6 treated mice showed almost 2-fold greater densities of serotonergic (5-HT) axons in the cortex compared to saline treated mice. Similar findings were observed in the catecholaminergic (TH) axons. Our results demonstrate that lowering of Aβ levels via passive Aβ immunotherapy ameliorates ongoing degenerative processes, supporting a causal link between Aβ and neurodegeneration.
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ying
Y
Liu
Michael K
MK
Lee
Maria M
MM
James
Donald L
DL
Price
David R
DR
Borchelt
Juan C
JC
Troncoso
Esther S
ES
Oh
D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001369:Axons / Q000473:pathology*; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D007116:Immunization, Passive; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000473:pathology / Q000628:therapy*; D018709:Statistics, Nonparametric
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000911:Antibodies, Monoclonal; D015306:Biogenic Monoamines