FTD Family Members Study & Post Mortem Study

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 • 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? Family Tree Key male female male affected by a dementia Deceased female who was affected by a dementia

7. Family Tree Key male D: 57 D: 89 female male affected by a dementia deceased female who was affected by a dementia D: 69 Dx: FTD D: 78 Dx: FTD D: 62 Dx: FTD Age: 73 D: 82 Age: 78 Age: 73 D: 77 Dx: FTD D: 79 D: 65 Dx: FTD D: 74 D: 82 Age: 79 Age: 65 Dx: FTD Age: 40 Age: 36 Age: 35 Family History #1 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 • FTD Post Mortem Imaging Study • Questions?

13. Thank you! • Thank you for your attention!