Disequilibrium of Tau Protein Phosphorylation and AD

Principal Investigator
Hemant Paudel, PhD
Lady Davis Institute for Medical Research
Montreal, Québec, Canada
About the Research Project
Program
Award Type
Standard
Award Amount
$200,000
Active Dates
April 01, 2002 - March 31, 2004
Grant ID
A2002038
Summary
In Alzheimer’s disease, neurofibrillary tangles (NTs) develop in nerve cells undergoing degeneration, and their distribution provides a reliable correlation to the degree of dementia. The molecular basis for the formation of NTs is not known. NTs contain paired helical filaments (PHFs) as the major fibrous component. The microtubule-associated protein tau is the major constituent of PHFs. It has been shown that tau abnormalities lead to neurodegeneration, microtubule disruption and dementia. This is thought to result from an imbalance in the phosphorylation of tau. The regulatory mechanisms that control tau phosphorylation and the determination of how this regulation fails in AD are not known. Dr. Paudel has recently identified a multiprotein complex in the brain that might be involved. He plans to characterize the proteins within this complex and determine their activities in tau phosphorylation with the goal of understanding the cascade of events that leads to abnormal tau phosphorylation, tau aggregation, microtubule disruption and neurodegeneration. Completion of this study will provide important information about the biochemical and cellular mechanisms of NT formation in the AD brain and help to design future treatment strategies to retard NT formation in the brains of AD patients.
Grants
Related Grants
Alzheimer's Disease Research
Regulatory Mechanisms Underlying Endosomal Targeting of SORL1
Active Dates
January 01, 2025 - December 31, 2026

Principal Investigator
Olav Andersen, PhD
Alzheimer's Disease Research
Synergistic Effects of Biological Sex and Sleep Loss in an AD Mouse Model
Active Dates
January 01, 2025 - December 31, 2026
Principal Investigator
Mallar Chakravarty, PhD
Alzheimer's Disease Research
The Role of DYRK1A in Altered Microglia Biology in a Cellular Model of Alzheimer’s Disease in Down Syndrome
Active Dates
January 01, 2025 - December 31, 2027

Principal Investigator
Frances Wiseman, PhD