Fork Neurons

Fork Neurons, a distinct type of neuron characterized by a single large basal dendrite and divided apical dendrite, are frequently found in brain regions alongside Von Economo neurons (VENs). In contrast to VENs, fork cells exhibit a unique dendritic structure. Frontotemporal dementia (FTD) presents with tau aggregation as a hallmark feature in some patients. Notably, individuals with sporadic behavioral variant FTD (bvFTD) due to frontotemporal lobar degeneration (FTLD), including FTLD with tau inclusions (FTLD-tau), experience early and selective loss of VENs and fork cells in the frontoinsular (FI) and anterior cingulate cortices (ACC). Recent findings also highlight the propensity for TDP-43 aggregation in these specialized neurons within FTLD-TDP. However, it remains unclear whether VENs and fork cells are susceptible to tau accumulation in FTLD-tau, especially in patients with pathogenic variants in the microtubule-associated protein tau gene (FTLD-tau/MAPT). In this study, we investigated tau aggregation and neurodegeneration in 40 brain regions among 8 FTLD-tau/MAPT patients and 7 with Pick's disease (PiD), a sporadic form of FTLD-tau often associated with bvFTD. Our qualitative assessment of frontoinsular tau aggregation in FTLD-tau/MAPT utilized antibodies targeting tau hyperphosphorylation, acetylation, or conformational changes. Regions notably affected by neurodegeneration and tau aggregation in both FTLD-tau/MAPT and PiD included the ACC and mid-insula.