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Malpetti, Maura; Rittman, Timothy; Jones, Peter Simon; Cope, Thomas Edmund; Passamonti, Luca; Bevan-Jones, William Richard; Patterson, Karalyn; Fryer, Tim D; Hong, Young T; Aigbirhio, Franklin I; O'Brien, John Tiernan; Rowe, James Benedict
Journal of neurology, neurosurgery and psychiatry, 03/2021, Volume: 92, Issue: 3Journal Article
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. Using positron emission tomography (PET), we explored the association of the distribution of activated microglia, as measured by the radioligand CPK11195, and the regional distribution of tau or TDP-43 pathology, indexed using the radioligand FAV-1451. The familial FTD PET data were compared with healthy controls. Patients with familial FTD across all mutation groups showed increased CPK11195 binding predominantly in frontotemporal regions, with additional regions showing abnormalities in individuals. Patients with MAPT mutations had a consistent distribution of FAV-1451 binding across the brain, with heterogeneous distributions among carriers of GRN and C9orf72 mutations. 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.
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