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. 2007 Oct-Dec;21(4):S50-7.
doi: 10.1097/WAD.0b013e31815c0f14.

Divergent social functioning in behavioral variant frontotemporal dementia and Alzheimer disease: reciprocal networks and neuronal evolution

William W Seeley  1 , John M Allman, Danielle A Carlin, Richard K Crawford, Marcelo N Macedo, Michael D Greicius, Stephen J Dearmond, Bruce L Miller
Affiliations

Divergent social functioning in behavioral variant frontotemporal dementia and Alzheimer disease: reciprocal networks and neuronal evolution

William W Seeley et al. Alzheimer Dis Assoc Disord. 2007 Oct-Dec.

Abstract

Behavioral variant frontotemporal dementia (bvFTD) disrupts our most human social and emotional functions. Early in the disease, patients show focal anterior cingulate cortex (ACC) and orbital frontoinsula (FI) degeneration, accentuated in the right hemisphere. The ACC and FI, though sometimes considered ancient in phylogeny, feature a large bipolar projection neuron, the von Economo neuron (VEN), which is found only in humans, apes, and selected whales-all large-brained mammals with complex social structures. In contrast to bvFTD, Alzheimer disease (AD) often spares social functioning, and the ACC and FI, until late in its course, damaging instead a posterior hippocampal-cingulo-temporal-parietal network involved in episodic memory retrieval. These divergent patterns of functional and regional impairment remain mysterious despite extensive molecular-level characterization of bvFTD and AD. In this report, we further develop the hypothesis that VENs drive the regional vulnerability pattern seen in bvFTD, citing recent evidence from functional imaging in healthy humans, and also structural imaging and quantitative neuropathology data from bvFTD and AD. Our most recent findings suggest that bvFTD and AD target distinct, anticorrelated intrinsic connectivity networks and that bvFTD-related VEN injury occurs throughout the ACC-FI network. We suggest that the regional and neuronal vulnerability patterns seen in bvFTD and AD underlie the divergent impact of these disorders on recently evolved social-emotional functions.

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