Cerebrovascular Dysfunction in Alzheimer's Disease and Transgenic Rodent Models.
Xing Fang1, Fan Fan2, Jane J Border1
1Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Journal of Experimental Neurology
|March 4, 2024
Summary
Alzheimer's Disease (AD) research is reappraising beta-amyloid's role, recognizing cerebrovascular dysfunction as a key factor. This review examines AD animal models and the interplay between Aβ and vascular contributions to AD pathogenesis.
Area of Science:
- Neuroscience
- Pathology
- Genetics
Background:
- Alzheimer's Disease (AD) and related dementias are leading causes of cognitive decline, imposing significant burdens.
- Hallmarks include beta-amyloid (Aβ) plaques and tau tangles, driving neurodegeneration and cognitive impairment.
- Familial AD mutations informed early transgenic models, but these don't fully capture sporadic AD pathology.
Purpose of the Study:
- To review the strengths and limitations of common transgenic AD animal models.
- To discuss current perspectives on the roles of Aβ accumulation and cerebrovascular dysfunction in AD pathogenesis.
- To highlight the growing importance of vascular contributions to AD.
Main Methods:
- Review of existing literature on AD pathogenesis and animal models.
- Analysis of the etiological contributions of Aβ and cerebrovascular factors.
- Evaluation of transgenic rodent models for AD research.
Main Results:
- Transgenic AD models offer insights but have limitations in replicating human AD.
- Aβ accumulation is not the sole driver; cerebrovascular dysfunction is an early and significant factor.
- A majority of AD cases are late-onset sporadic, underscoring the need to look beyond familial mutations.
Conclusions:
- Reappraisal of AD pathogenesis is necessary, moving beyond a sole focus on Aβ.
- Cerebrovascular dysfunction is increasingly recognized as a critical component in AD development.
- Future research and therapeutic strategies should consider both Aβ and vascular pathology.
Keywords:
AD animal modelsAlzheimer’s diseaseBeta-amyloidBrain hypoperfusionCerebrovascular dysfunctionNeurovascular couplingTauMore Related Videos
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