1. FTD Family Members Study & Post Mortem Study Alyson Negreira MGH Frontotemporal Disorders Unit

2. Topics FTD Family Members Study Post Mortem Imaging Study

3. Topics FTD Family Members Study

4. FTD Family Members Study—Phase 1 We have begun a study that investigates the heritability, genetics, and expression of FTD in families in which a patient with FTD has 1 or more blood relatives that are/were affected by a dementia or other neurodegenerative disease (e.g., Parkinson’s, ALS, etc).. Primary goal: To identify new genes involved in the inheritance of FTD To better understand the effects of known genes on the expression of FTD To identify the earliest changes in cognitive/neurologic function in family members who were initially unaffected but who develop symptoms Procedures: Detailed review of family history NACC (National Alzheimer’s Coordinating Center) - involves an annual clinical assessment, neurologic exam, and neuropsychological assessment to measure and monitor cognitive functioning Harvard Biomarkers Study - a blood draw including testing for different genes and proteins (research, not clinical).

5. FTD Family Members Study FTD Family Members Study—Phase 2 We are working to add two new components to the study. Neuroimaging study: To identify changes in brain structure or function (using fMRI & PET) in individuals as the symptoms of FTD begin to develop To try to identify these changes prior to the development of symptoms Procedures would involve scans every 1-2 years in family members iPS study: Induced pluripotent stem cells… --skin biopsy (minor procedure, local anesthesia) --skin cells grown in lab, transformed into brain cells --can be investigated to identify molecular problems in that individual

6. FTD Family Members Study Why is this important? male female male affected by a dementia Deceased female who was affected by a dementia Family Tree Key

7. Family History #1 D: 57D: 89 D: 69 Dx: FTD D: 78 Dx: FTD D: 65 Dx: FTD D: 62 Dx: FTD D: 77 Dx: FTD Age: 65 Dx: FTD D: 82 D: 79 D: 74 Age: 78 Age: 73 D: 82Age: 79 Age: 40Age: 35Age: 36 male female male affected by a dementia deceased female who was affected by a dementia Family Tree Key anonymized to protect confidentiality

8. Topics FTD Family Members Study Questions?

9. Topics Post Mortem Imaging Study

10. MGH Brain Bank Procedures Currently: Detailed pathology analysis is performed after death We review report with family Pathology reports let families know what the underlying protein is that was causing the dementia Various types of research is done with brain tissue Why is this important? Pathology reports: In some cases, a patient can present with features of FTD, however upon autopsy they have Alzheimer’s Disease pathology

11. FTD Post Mortem Imaging Study Primary Goal: To better link imaging measures that can be obtained in living people to measures of brain pathology that can only be obtained after death Procedures: A series of MRI scans at higher and higher resolution (whole brain, targeted portions of brain most affected by disease) Photographs of brain sections (can be aligned with scans) Use these methods to link the two types of measures

12. FTD Post Mortem Imaging Study Questions?

13. Thank you! Thank you for your attention!