2009 Grants - Boutajangout

Influence of Presenilin Mutation on Tau Pathology

Allal Boutajangout, Ph.D.
New York University School of Medicine
New York, New York

2009 New Investigator Research Grant

Presenilin 1 (PS1) is an enzyme that is an important focus of research on Alzheimer's disease; mutations in PS1 are the most common cause of early-onset forms of the disease. Mutations in PS1 cause an increase in production of beta-amyloid, a peptide fragment that aggregates to form amyloid plaques, a characteristic feature of Alzheimer pathology. The biochemical pathway mediating this effect is well understood. Cells with PS1 mutations also exhibit neurofibrillary tangles, another characteristic feature of Alzheimer pathology. However, the biochemical pathway mediating the formation of neurofibrillary tangles after mutation of PS1 is not well understood.

Allal Boutajangout, Ph.D. and colleagues have proposed to study the mechanisms of neurofibrillary tangle formation resulting from a mutation of PS1. For these studies, the researchers will examine neurofibrillary tangle formation in mice that have been genetically altered to express the human gene for a protein known as tau, which is the primary component of neurofibrillary tangles. The researchers will also induce a mutation in the PS1 gene, thereby creating a mouse model of neurofibrillary tangle formation induced by PS1 mutation.

Dr. Boutajangout's team will assess how the PS1 mutation affects cognitive function and brain pathology at different times. The researchers will also examine the biochemical pathways involved in the formation of neurofibrillary tangles in order to understand how PS1 mutations affect these pathways. These studies could shed light on a key biochemical pathway leading to brain pathology in early-onset Alzheimer's disease.