THE ROLE OF CLC-3 CHLORIDE CHANNELS IN THE PROGRESSION OF THE 5XFAD ALZHEIMER’S DISEASE MOUSE MODEL

Restricted (Penn State Only)
Author:
Parry, Matthew
Area of Honors:
Biomedical Engineering
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Gong Chen, Thesis Supervisor
  • Jian Yang, Honors Advisor
  • Kevin Douglas Alloway, Honors Advisor
Keywords:
  • CLC-3
  • Chloride Channels
  • Alzheimer's disease
  • Amyloid Beta
  • Aβ42
  • β-secretase
  • Beta Secretase
  • BACE1
Abstract:
Alzheimer’s disease is currently the sixth leading killer in the United States and will likely increase as the demographic becomes older in the coming years. Aloysius Alzheimer first characterized the disease in the early 1900’s, where he noted memory deficits before a patient’s death and fibrous plaque formation throughout most of the human brain upon autopsy. Since its discovery only symptom-related therapies have been approved for prescription to patients with the disease, with truthfully little benefit to the patient. Therapies targeting the cholinergic deficits in the disease are the primary drugs available, however, they do nothing to prevent disease progression, and instead only minimally improve the patient’s life during the early stages for a short period of time. No cure exists for the condition, primarily because the scientific community remains puzzled by its inception and ensuing mechanisms of progression. Here, I describe a novel role of the CLC-3 chloride channel in the progression of the Alzheimer’s disease pathology in the 5XFAD mouse model. Without the anion channel in knockdown viral expressions and knockout mice models, the pace of disease progression reduces dramatically. Conversely, an increase of the channel by viral overexpression can greatly accelerate the disease progression in mice models, marked by increased amyloid plaque deposition. Our finding could be beneficial in understanding the development of Alzheimer’s disease and may therefore bring the community closer to a viable treatment for the neurodegenerative disorder.