Abstract
The accumulation of amyloid-β into insoluble plaques is a characteristic feature of Alzheimer's disease. Neuronal morphology is distorted by plaques: rather than being essentially straight, they are substantially more curved than those in control tissue, their trajectories become altered, and they are frequently distended or swollen, presumably affecting synaptic transmission. Clearance of plaques by administration of antibodies to amyloid-β is a promising therapeutic approach to the treatment of Alzheimer's disease, leading to stabilization of dementia by an unknown cellular mechanism. The effect of plaque clearance on plaque-induced neuronal alterations has not been studied previously. Here we show that both plaques and neuritic lesions are reversible in a strikingly short period of time after administration of a single dose of amyloid-β antibody. Amyloid clearance and recovery of normal neuronal geometries were observed as early as 4 d and lasted at least 32 d after a single treatment. These results demonstrate that, once plaques are cleared, neuronal morphology is self-correcting and that passive antibody treatment has the potential to reverse neuronal damage caused by Alzheimer's disease and, hence, directly impact cognitive decline. Moreover, the rapid normalization of neuritic dystrophy suggests an unexpected degree of plasticity in the adult nervous system.
References
20
Referenced
119
10.1038/85525
10.1523/JNEUROSCI.22-18-07873.2002
10.1002/cne.902820204
10.1093/jnen/62.2.137
/ J Neuropathol Exp Neurol (2003)10.1038/373523a0
10.1016/S0896-6273(03)00294-0
10.1126/science.274.5284.99
10.1097/00005072-199201000-00009
10.1523/JNEUROSCI.17-18-07053.1997
{'key': '2023041303040718000_23.34.10879.10', 'first-page': '373', 'volume': '138', 'year': '1991', 'journal-title': 'Am J Pathol'}
/ Am J Pathol (1991)10.1097/00005072-199812000-00003
10.1073/pnas.96.9.5274
10.1093/jnen/60.8.753
10.1093/jnen/60.4.357
10.1111/j.1749-6632.2000.tb05559.x
/ Ann NY Acad Sci (2000)10.1038/nm840
10.1007/s004010050737
10.1074/jbc.271.31.18295
10.1016/S0896-6273(02)00652-9
10.1038/nature01273
Dates
Type | When |
---|---|
Created | 7 years, 4 months ago (April 13, 2018, 6:30 p.m.) |
Deposited | 1 year, 1 month ago (July 5, 2024, 8:53 p.m.) |
Indexed | 3 months, 3 weeks ago (May 13, 2025, 12:30 p.m.) |
Issued | 21 years, 9 months ago (Nov. 26, 2003) |
Published | 21 years, 9 months ago (Nov. 26, 2003) |
Published Online | 21 years, 9 months ago (Nov. 26, 2003) |
Published Print | 21 years, 9 months ago (Nov. 26, 2003) |
@article{Lombardo_2003, title={Amyloid-β Antibody Treatment Leads to Rapid Normalization of Plaque-Induced Neuritic Alterations}, volume={23}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.23-34-10879.2003}, DOI={10.1523/jneurosci.23-34-10879.2003}, number={34}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Lombardo, Julianne A. and Stern, Edward A. and McLellan, Megan E. and Kajdasz, Stephen T. and Hickey, Gregory A. and Bacskai, Brian J. and Hyman, Bradley T.}, year={2003}, month=nov, pages={10879–10883} }