Dendrite and dendritic spine alterations in alzheimer models
Abstract
Synaptic damage and loss are factors that affect the degree of dementia experienced in Alzheimer disease (AD) patients. Multicolor DiOlistic labeling of the hippocampus has been undertaken which allows the full dendritic arbor of targeted neurons to be imaged. Using this labeling technique the neuronal morphology of two transgenic mouse lines (J20 and APP/PS1) expressing mutant forms of the Amyloid Precursor Protein (APP), at various ages, have been visualized and compared to Wild Type (WT) littermate controls. Swollen bulbous dystrophic neurites with loss of spines were apparent in the transgenic animals. Upon quantification, statistically significant reductions in the number of spines and total dendrite area was observed in both transgenic mouse lines at 11 months of age. Similar morphological abnormalities were seen in human AD hippocampal tissue both qualitatively and quantitatively. Immunohistochemistry and DiOlistic labeling was combined so that Abeta plaques were imaged in relation to the dendritic trees. No preferential localization of these abnormal dystrophic neurites was seen in regions with plaques. DiI labeled reative astrocytes were often apparent in close proximity to A beta plaques.
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Dendritic spine loss occurs in APP transgenic models.
“Dendritic spine loss occurs in APP transgenic models (Lanz et al., 2003;Moolman et al., 2004;Tsai et al., 2004), an important observation because spines form the postsynaptic element of the vast majority of cortical synapses and are the proposed site of synaptic plasticity underlying learning and memory (Segal, 2002).”
From Dendritic Spine Abnormalities in Amyloid Precursor Protein Transgenic Mice Demonstrated by Gene Transfer and Intravital Multiphoton Microscopy (2005) · cites this paper as Moolman et al., 2004
AD transgenic mice showed physiological and neuritic alterations prior to plaques.
“AD transgenic mice showed physiological [32, 74, 77, 124] and neuritic alterations [22, 125] prior to plaques”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [125]
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- Authors
- Moolman, D. L., Vitolo, O. V., Vonsattel, J.-P. G., & Shelanski, M. L.
- Affiliations
- Columbia University (US)
- Corresponding author
- Shelanski, Michael L.
- Venue
- Journal of Neurocytology
- Published
- 2004-05
- Volume
- 33
- Issue
- 3
- Pages
- 377-387
- ISSN
- 0300-4864 (ISSN-L)
- 1573-7381
- OpenAlex
- W1967917932
- Cited by
- 245
- References
- 33
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 5 · 2023: 9 · 2022: 13 · 2021: 7 · 2020: 10 · 2019: 7 · 2018: 8 · 2017: 9 · 2016: 14 · 2015: 15 · 2014: 16 · 2013: 23 · 2012: 11
- FWCI
- 5.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Neurocytology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG08702, P50AG008702)
- National Institute of Neurological Disorders and Stroke (NS15076, R01NS015076)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, dendritic spine loss, dendritic morphology, amyloid precursor protein, APP/PS1 mice, dystrophic neurites, amyloid plaques, hippocampus, reactive astrocytes, synaptic damage, DiI labeling
- MeSH terms
- Aging, Alzheimer Disease, Animals, Astrocytes, Carbocyanines, Dendrites, Disease Models, Animal, Hippocampus, Humans, Immunohistochemistry, Mice, Transgenic, Mutation, Staining and Labeling, Amyloid beta-Protein Precursor, Pyramidal Cells, Biolistics, Dendritic Spines, Mice, Plaque, Amyloid
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