PROJECT SUMMARY/ABSTRACT: CORE A The overarching theme of this program project renewal entitled “Pathobiology of Neurodegeneration in C9ORF72 Repeat Expansion” is to determine the mechanisms by which C9orf72 repeat expansions cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), and identify novel therapeutic targets and biomarkers in order to improve the diagnosis of and prognosis for patients suffering from c9ALS/FTD. Core A will facilitate these goals by providing scientific and fiscal oversight. Core A will be responsible for managing fiscal responsibilities for the program project, ensuring ethical and responsible conduct of research, providing scientific direction and accountability, and reporting progress to the NIH and to the public. To assure the success of this research proposal, Core A will also foster a multidisciplinary program that advances research, generates valuable biological resources, and promotes education. To accomplish its goals, Core A will pursue the following specific aims. Specific Aim 1: Provide administrative structure and fiscal oversight for the program project grant. Specific Aim 2: Organize regular meetings of the Executive Committee to assist in the scientific administration and to facilitate integration and continuing progress on research aims. Specific Aim 3: Establish an External Advisory Committee, conduct annual meetings, and report progress to the NINDS. Specific Aim 4: Ensure that the clinical research conforms to the standards of the ethical conduct of research and the safety of human subjects. Specific Aim 5: Report progress to NIH and ensure compliance with the NIH Public Access policy. Specific Aim 6: Promote education on ALS and related disorders, and encourage P01 scientists and clinicians to participate in patient and caregiver support groups.