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Early Frontotemporal Dementia Targets Neurons Unique to Apes and Humans
 

Summary: Early Frontotemporal Dementia Targets
Neurons Unique to Apes and Humans
William W. Seeley, MD,1
Danielle A. Carlin, BA,1
John M. Allman, PhD,2
Marcelo N. Macedo, BS,1
Clarissa Bush, BA,3
Bruce L. Miller, MD1
and Stephen J. DeArmond, MD, PhD,3
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 mo-
lecular 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 immuno-
histochemical 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 patho-
logical subtypes. Surviving VENs were often dysmorphic, with pathological tau protein accumulation in Pick's disease. In

  

Source: Allman, John M. - Division of Biology, California Institute of Technology

 

Collections: Biology and Medicine