Abstract
INTRODUCTION: We report in vivo patterns of neuroinflammation and abnormal protein aggregation in seven cases of familial frontotemporal dementia (FTD) with mutations in MAPT, GRN and C9orf72 genes. METHODS: Using positron emission tomography (PET), we explored the association of the distribution of activated microglia, as measured by the radioligand [(11)C]PK11195, and the regional distribution of tau or TDP-43 pathology, indexed using the radioligand [(18)F]AV-1451. The familial FTD PET data were compared with healthy controls. RESULTS: Patients with familial FTD across all mutation groups showed increased [(11)C]PK11195 binding predominantly in frontotemporal regions, with additional regions showing abnormalities in individuals. Patients with MAPT mutations had a consistent distribution of [(18)F]AV-1451 binding across the brain, with heterogeneous distributions among carriers of GRN and C9orf72 mutations. DISCUSSION: This case series suggests that neuroinflammation is part of the pathophysiology of familial FTD, warranting further consideration of immunomodulatory therapies for disease modification and prevention.