Dr. Schellenberg and his laboratory use genetic approaches to understand diseases that affect the central nervous system.  A major effort of his group is focused on Alzheimer’s disease and closely related disorders.  He is using linkage and association analysis to identify susceptibility genes for late-onset Alzheimer’s disease.  His work in the past resulted in the identification and cloning of the early-onset Alzheimer’s disease genes presenilin 1 and 2.  He is also looking for genes that modify the penetrance of presenilin 1 and 2 mutations.  Other projects in Dr. Schellenberg’s group include working on the genetic and mechanistic basis for tauopathies such as frontotemporal dementia, progressive supra nuclear palsy, and a Guam amyotrophic lateral sclerosis - parkinsonism dementia complex (ALS-PDC).  His group and others previously identified mutations in tau that cause some cases of FTD.  For Guam ALS-PDC, tau polymorphic sites influence risk for this disorder.   Linkage analysis is being used to identify the major gene for Guam ALS-PDC.  He is now working on generating transgenic mouse models of tauopathies.  These models are being used to study the influence of tau mutations and expression on behavior, neuropathology, and developmental and regional expression of tau in the brain.  Dr. Schellenberg is also collaborating with Dr. Brian Kraemer on a C. elegans model of tauopathies.  This models are being used to explore the mechanism of neurodegeneration and to identify genes that modify the tau-induced behaviors and pathology in the C. elegans model.  Another project in the Schellenberg group is attempting to find susceptibility genes for schizophrenia. The overarching theme of Dr. Schellenberg’s work is to use genetic methods to identify genes and their corresponding pathways that contribute to diseases of the central nervous system.  These pathways when identified become the focus of discovery efforts for finding new drugs for treating these critical diseases.