In vivo PET imaging of neuroinflammation in familial frontotemporal dementia.

Introduction: We report 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 [C]PK11195, and the regional distribution of tau or TDP-43 pathology, indexed using the radioligand [F]AV-1451. The familial FTD PET data were compared with healthy controls.

Results: Patients with familial FTD across all mutation groups showed increased [C]PK11195 binding predominantly in frontotemporal regions, with additional regions showing abnormalities in individuals. Patients with MAPT mutations had a consistent distribution of [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.