To view an abstract, select an author from the vertical list on the left.
2010 Grants - Conrad
The Role of SorLA in Tau Aggregation
Christopher Conrad, Ph.D.
New York, New York
2010 New Investigator Research Grant
Two hallmarks of Alzheimer's disease are the formation of plaques, which contain the protein fragment beta-amyloid, and neurofibrillary tangles, which contain abnormal tau protein. Much research has been devoted to the search for genes that make people more susceptible to Alzheimer pathology. Recent studies have found that variants of a gene called sorLA may be responsible for excessive beta-amyloid production. SorLA protein helps regulate the normal transport of amyloid precursor protein (APP), the "parent" molecule of beta-amyloid, around the cell. But certain variants of the sorLA gene have been associated with reduced brain levels of sorLA protein. When such protein levels are low, APP molecules may cluster in compartments of the cell where they become processed into beta-amyloid.
Based on results from their recent studies, Christopher Conrad, Ph.D., and colleagues hypothesize that decreased sorLA expression may also lead to the overproduction of abnormal tau protein—and the development of neurofibrillary tangles. For this grant, the researchers propose to test their hypothesis. They also plan to determine the biological mechanisms that may underlie lowered sorLA protein levels and increased levels of abnormal tau. Their study will examine cultured cells, autopsied human brain tissue and mice engineered to develop Alzheimer-like pathologies.
The results of this research could add greatly to our understanding of the genetic underpinnings of Alzheimer pathology. The work could also lead to new genetic treatments for dementia.