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Divergent Social Functioning in Behavioral Variant Frontotemporal Dementia and Alzheimer Disease: Reciprocal Networks and Neuronal Evolution

Seeley, William W. and Allman, John M. and Carlin, Danielle A. and Crawford, Richard K. and Macedo, Marcelo N. and Greicius, Michael D. and DeArmond, Stephen J. and Miller, Bruce L. (2007) Divergent Social Functioning in Behavioral Variant Frontotemporal Dementia and Alzheimer Disease: Reciprocal Networks and Neuronal Evolution. Alzheimer Disease and Associated Disorders: An International Journal, 21 (4). S50-S57. ISSN 0893-0341. doi:10.1097/WAD.0b013e31815c0f14.

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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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Additional Information:© 2007 Lippincott Williams & Wilkins, Inc. Supported by the National Institute of Aging grants K08 AG027086-01, 1P01 AG19724-01A1, and P50 AG1657303-75271, Larry L. Hillblom Foundation, James S. McDonnell Foundation, Doris Duke Foundation, Gordon and Betty Moore Foundation, and the David and Lucile Packard Foundation. The authors thank Archibald Fobbs of the National Museum of Health and Medicine for his assistance at the Yakovlev-Haleem Collection and Michael Fox and Daniel Marcus for help with the BrainSCAPE website.
Funding AgencyGrant Number
NIHK08 AG027086-01
NIH1P01 AG19724-01A1
NIHP50 AG1657303-75271
Larry L. Hillblom FoundationUNSPECIFIED
James S. McDonnell FoundationUNSPECIFIED
Doris Duke FoundationUNSPECIFIED
Gordon and Betty Moore FoundationUNSPECIFIED
David and Lucile Packard FoundationUNSPECIFIED
National Institute of AgingUNSPECIFIED
Subject Keywords:von Economo neuron; frontotemporal dementia; Alzheimer disease; anterior cingulate; frontoinsula
Issue or Number:4
Record Number:CaltechAUTHORS:20101104-145047505
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:20677
Deposited By: Jason Perez
Deposited On:05 Nov 2010 17:26
Last Modified:09 Nov 2021 00:02

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