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Grants > Amyloid Plaque Degradation by Matrix Metalloproteinase9 Updated On: Jan. 19, 2025
Alzheimer's Disease Research Grant

Amyloid Plaque Degradation by Matrix Metalloproteinase9

Principal Investigator

Jin-moo Lee, MD, PhD

Washington University in St.Louis

St. Louis, MO, United States

About the Research Project

Program

Alzheimer's Disease Research

Award Type

Standard

Award Amount

$300,000

Active Dates

April 01, 2006 - March 31, 2008

Grant ID

A2006033

Goals

Since Dr. Alois Alzheimer initially described the disease that bears his names, amyloid plaques have been a hallmark of the disease. Dr. Lee’s team is investigating the role of a specific enzyme believed to be involved in controlling rate of plaque growth. The inquiry into nature’s way of eliminating toxic amyloid will offer scientists new opportunities to leverage this process in future therapeutics.

Summary

One of the major abnormalities found in the brains of patients with Alzheimer’s disease (AD) are clumps of abnormally aggregated protein, called amyloid plaques. These proteins (amyloid-beta peptide) have a remarkable propensity to self-aggregate into long chains of protein known as amyloid fibrils, which are thought to be very resistant to breakdown and clearance. Thus, it is believed that the plaques accumulate in the brains of patients with Alzheimer’s disease, contributing to brain degeneration and leading to dementia. Dr. Lee has recently found an enzyme, matrix metalloproteinase-9 (MMP-9), capable of degrading amyloid fibrils in test tube experiments. He has also found that MMP-9 degrades amyloid plaques in brain slices from a mouse model of AD. Furthermore, he finds that this enzyme is found in cell surrounding amyloid plaques in this mouse model, suggesting that it may play a role in regulating the growth of plaques. In this grant application, Dr. Lee proposes to study the role of MMP-9 in degrading amyloid plaques in a mouse model of Alzheimer’s disease. He plans to use genetically altered AD mice that lack MMP-9 to examine the formation of amyloid plaques, asking the question: “Is plaque formation accelerated in AD mice that lack MMP-9?” Furthermore, this research will determine if MMP-9 limits the size of amyloid plaques once they are formed. Dr. Lee hopes to gain further insight into mechanisms that regulate the growth and degradation of amyloid plaques in Alzheimer’s disease.