Amyloid-β Antibody Treatment Leads to Rapid Normalization of Plaque-Induced Neuritic Alterations
Open accessAbstract
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.
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Treatment with anti-Aβ antibodies in APP transgenic mice can straighten the trajectory of neurites.
“straighten the trajectory of neurites (Lombardo et al., 2003)”
From Dendritic Spine Abnormalities in Amyloid Precursor Protein Transgenic Mice Demonstrated by Gene Transfer and Intravital Multiphoton Microscopy (2005) · cites this paper as Lombardo et al., 2003
Resolution of soluble forms of tau is sufficient to normalize morphology of dystrophic neurites around plaques.
“Another example of tau-related lesions, the dystrophic neurites around plaques, also implicates the role of soluble rather than fibrillar species since the resolution of soluble forms of tau is sufficient to lead to normalization of the morphology (25, 53).”
From All the Tau We Cannot See (2023) · cites this paper as [53]
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- Authors
- Lombardo, J. A., Stern, E. A., McLellan, M. E., Kajdasz, S. T., Hickey, G. A., Bacskai, B. J., & Hyman, B. T.
- Affiliations
- Massachusetts General Hospital (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-11-26
- Volume
- 23
- Issue
- 34
- Pages
- 10879-10883
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6740984
- OpenAlex
- W1667130205
- Cited by
- 149
- References
- 20
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 3 · 2017: 1 · 2016: 3 · 2015: 1 · 2014: 4 · 2013: 7 · 2012: 3
- FWCI
- 8.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AG08487)
- National Institute on Aging (AG-08487, AG 15453, R01AG008487, P01AG015453, R01AG020570, AG 020570)
- National Institute of Biomedical Imaging and Bioengineering (EB-00768, R01EB000768)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- amyloid-beta antibodies, amyloid plaques, Alzheimer's disease, neuritic dystrophy, neuronal morphology, plaque clearance, passive immunotherapy, neuroplasticity, cognitive decline, synaptic transmission
- MeSH terms
- Age Factors, Alzheimer Disease, Animals, Antibodies, Cerebral Cortex, Disease Models, Animal, Drug Administration Routes, Humans, Immunization, Passive, Mice, Inbred C57BL, Mice, Transgenic, Neuronal Plasticity, Amyloid beta-Peptides, Neurites, Treatment Outcome, Mice, Plaque, Amyloid
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