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Updated: Jan 3, 2026
Longitudinal In Vivo Imaging of the Cerebrovasculature: Relevance to CNS Diseases
Published on: December 6, 2016
Microvessel occlusions alter amyloid-beta plaque morphology in a mouse model of Alzheimer's disease
Yuying Zhang1, Evan D Bander1, Yurim Lee1
1Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
Abstract:
Vascular dysfunction is correlated to the incidence and severity of Alzheimer's disease. In a mouse model of Alzheimer's disease (APP/PS1) using in vivo, time-lapse, multiphoton microscopy, we found that occlusions of the microvasculature alter amyloid-beta (Aβ) plaques. We used several models of vascular injury that varied in severity. Femtosecond laser-induced occlusions in single capillaries generated a transient increase in small, cell-sized, Aβ deposits visualized with methoxy-X04, a label of fibrillar Aβ. After occlusions of penetrating arterioles, some plaques changed morphology, while others disappeared, and some new plaques appeared within a week after the lesion. Antibody labeling of Aβ revealed a transient increase in non-fibrillar Aβ one day after the occlusion that coincided with the disappearance of methoxy-X04-labeled plaques. Four days after the lesion, anti-Aβ labeling decreased and only remained in patches unlabeled by methoxy-X04 near microglia. Histology in two additional models, sparse embolic occlusions from intracarotid injections of beads and infarction from photothrombosis, demonstrated increased labeling intensity in plaques after injury. These results suggest that microvascular lesions can alter the deposition and clearance of Aβ and confirm that Aβ plaques are dynamic structures, complicating the interpretation of plaque burden as a marker of Alzheimer's disease progression.
Insights
Microvascular injury in Alzheimer's disease models alters amyloid-beta (Aβ) plaques, affecting their deposition and clearance. These findings suggest Aβ plaques are dynamic, challenging their use as a sole progression marker.
Area of Science:
- Neuroscience
- Vascular Biology
- Biomedical Engineering
Background:
- Vascular dysfunction is linked to Alzheimer's disease (AD) incidence and severity.
- Amyloid-beta (Aβ) plaques are a hallmark of AD, but their dynamic nature is not fully understood.
Purpose of the Study:
- To investigate how microvascular occlusions impact amyloid-beta (Aβ) plaque dynamics in a mouse model of Alzheimer's disease.
- To determine if vascular lesions affect Aβ plaque deposition, morphology, and clearance.
Main Methods:
- Utilized in vivo, time-lapse, multiphoton microscopy in APP/PS1 Alzheimer's disease mouse models.
- Induced microvascular occlusions using femtosecond laser, embolic injections, and photothrombosis.
- Visualized fibrillar Aβ with methoxy-X04 and non-fibrillar Aβ using antibody labeling.
Main Results:
- Capillary occlusions transiently increased small Aβ deposits.
- Arteriolar occlusions led to plaque morphological changes, disappearance, and new plaque formation.
- A transient increase in non-fibrillar Aβ coincided with the disappearance of fibrillar plaques post-occlusion.
- Histology confirmed increased plaque labeling intensity after various vascular injury models.
Conclusions:
- Microvascular lesions dynamically alter amyloid-beta plaque deposition and clearance.
- Aβ plaques are not static; their burden may be a complex and unreliable marker for Alzheimer's disease progression.
- Understanding the interplay between vasculature and Aβ is crucial for AD research and therapeutic strategies.
