Exploring Alzheimer’s disease in the tg-ArcSwe model with a vascular, hormonal and neuromodulatory perspective

• Main Author: Skaaraas, Gry Helen Enger Syverstad
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: 2023
• Subjects: Arctic
• Online Access: http://hdl.handle.net/10852/102734

Alzheimer’s Disease (AD) is the major cause of dementia, and abnormal amyloid-β (Aβ) protein is the main component of the pathological plaques found in the brain parenchyma of these patients. However, disappointing results from many clinical trials have made it clear that Aβ alone cannot explain the pathogenesis of the disease. Multiple factors are today considered to contribute to Aβ pathology, and the aim of Skaaraas’ doctoral thesis was to explore the disease from a hormonal, vascular and neuromodulatory angle to gain a deeper understanding of the role of these factors in AD. Skaaraas has studied the spatial distribution and variance of Aβ plaques and cerebral amyloid angiopathy in the transgenic Arctic Swedish mouse model (tg-ArcSwe). Her studies demonstrate dysfunctional norepinephrine-astrocyte Ca2+ activity in tg-ArcSwe mice, a signaling system of relevance for higher cognitive functions, and provide evidence implicating hormonal and vascular factors in the pathogenesis of AD. These novel results indicate that synergies between several factors are relevant in AD, and that further experimental research may benefit from more multimodal approaches.