2011 Grants - Kaur

Intracellular Oligomeric Abeta and Endosomal Pathology in APPE693Q Mice

Gurjinder Kaur, Ph.D.
The Nathan S. Kline Institute for Psychiatric Research
Orangeburg, New York

2011 Investigator-Initiated Research Grant

Beta-amyloid (also known as Abeta) is a protein fragment that aggregates into amyloid plaques, one of the hallmarks of Alzheimer's pathology. Before amyloid plaques form, however, beta-amyloid aggregates into smaller structures known as oligomers. Recent evidence suggests that beta-amyloid oligomers begin to form inside nerve cells, within structures known as endosomes.

Gurjinder Kaur, Ph.D. and colleagues have proposed to study how beta-amyloid oligomers in nerve cell endosomes contribute to the development of Alzheimer's pathology. Using mice that have been genetically altered to overexpress beta-amyloid, the researchers will examine the time course of different brain pathologies including formation of beta-amyloid oligomers, nerve cell dysfunction and neurodegeneration.

Dr. Kaur's team also plans to study the role of a protein that might protect nerve cells from damage caused by beta-amyloid oligomers. This protein, known as cystatin C, is expressed in all cells and there is some evidence that it may prevent the formation of beta-amyloid oligomers. The researchers plan to create new strains of mice that overexpress both beta-amyloid and cystatin C to determine if cystatin C alleviates the pathologic changes associated with beta-amyloid. These studies will advance our understanding of the disease process and may suggest strategies to slow or prevent the progression of Alzheimer's pathology.