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Early frontotemporal dementia targets neurons unique to apes and humans

Seeley, William W. and Carlin, Danielle A. and Allman, John M. and Macedo, Marcelo N. and Bush, Clarissa and Miller, Bruce L. and DeArmond, Stephen J. (2006) Early frontotemporal dementia targets neurons unique to apes and humans. Annals of Neurology, 60 (6). pp. 660-667. ISSN 0364-5134. https://resolver.caltech.edu/CaltechAUTHORS:20201103-124307200

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Abstract

Objective: Frontotemporal dementia (FTD) is a neurodegenerative disease that erodes uniquely human aspects of social behavior and emotion. The illness features a characteristic pattern of early injury to anterior cingulate and frontoinsular cortex. These regions, though often considered ancient in phylogeny, are the exclusive homes to the von Economo neuron (VEN), a large bipolar projection neuron found only in great apes and humans. Despite progress toward understanding the genetic and molecular bases of FTD, no class of selectively vulnerable neurons has been identified. Methods: Using unbiased stereology, we quantified anterior cingulate VENs and neighboring Layer 5 neurons in FTD (n = 7), Alzheimer's disease (n = 5), and age‐matched nonneurological control subjects (n = 7). Neuronal morphology and immunohistochemical staining patterns provided further information about VEN susceptibility. Results: FTD was associated with early, severe, and selective VEN losses, including a 74% reduction in VENs per section compared with control subjects. VEN dropout was not attributable to general neuronal loss and was seen across FTD pathological subtypes. Surviving VENs were often dysmorphic, with pathological tau protein accumulation in Pick's disease. In contrast, patients with Alzheimer's disease showed normal VEN counts and morphology despite extensive local neurofibrillary pathology. Interpretation: VEN loss links FTD to its signature regional pattern. The findings suggest a new framework for understanding how evolution may have rendered the human brain vulnerable to specific forms of degenerative illness.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1002/ana.21055DOIArticle
Additional Information:© 2006 American Neurological Association. Received Nov 10, 2006, and in revised form Nov 14. Accepted for publication Nov 14, 2006. This work was supported by the NIH (National Institute on Aging, K08 AG027086‐01, W.W.S.; P01 AG19724‐01A1, B.L.M.; P50 AG1657303‐75271, S.J.D., B.L.M.), the Larry L. Hillblom Foundation (2005/2T, W.W.S.), Doris Duke Foundation (D.A.C.), and the Gordon and Betty Moore Foundation and David and Lucile Packard Foundation (J.M.A.). The University of California at Irvine Alzheimer's Disease Research Center Neuropathology Core is supported by funding from NIH/NIA P50A916573 and the Institute for Brain Aging and Dementia Tissue Resource is supported by NIH/NIA PO14600538. We thank E. Head, J. Kaufman, K. Watson, E. Huang, J. Johnson, M. Sattavat, and J. Neuhaus for assistance and E. Roberson and H. Slama for comments on the manuscript. Finally, we thank our patients and their families for participating in dementia research.
Funders:
Funding AgencyGrant Number
NIHK08 AG027086-01
NIHP01 AG19724-01A1
NIHP50 AG1657303-75271
Larry L. Hillblom FoundationUNSPECIFIED
Doris Duke FoundationUNSPECIFIED
Gordon and Betty Moore FoundationUNSPECIFIED
David and Lucile Packard FoundationUNSPECIFIED
NIHP50A916573
NIHPO14600538
Issue or Number:6
Record Number:CaltechAUTHORS:20201103-124307200
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201103-124307200
Official Citation:Seeley, W.W., Carlin, D.A., Allman, J.M., Macedo, M.N., Bush, C., Miller, B.L. and DeArmond, S.J. (2006), Early frontotemporal dementia targets neurons unique to apes and humans. Ann Neurol., 60: 660-667. doi:10.1002/ana.21055
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:106400
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:04 Nov 2020 20:33
Last Modified:04 Nov 2020 20:33

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