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Open Access Research

The pathogenesis of cingulate atrophy in behavioral variant frontotemporal dementia and Alzheimer’s disease

Rachel H Tan1, Karen Pok2, Stephanie Wong1, Daniel Brooks13, Glenda M Halliday13 and Jillian J Kril24*

Author Affiliations

1 Neuroscience Research Australia, Barker Street, Randwick, Sydney, NSW 2031, Australia

2 Discipline of Pathology, Sydney Medical School, The University of Sydney, Sydney, NSW 2206, Australia

3 School of Medical Sciences, University of New South Wales, Sydney, Australia

4 Discipline of Medicine, Sydney Medical School, The University of Sydney, Sydney, Australia

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Acta Neuropathologica Communications 2013, 1:30  doi:10.1186/2051-5960-1-30

Published: 5 July 2013

Abstract

Background

Early atrophy of the cingulate cortex is a feature of both behavioral variant frontotemporal dementia (bvFTD) and Alzheimer’s disease (AD), with degeneration of the anterior cingulate region increasingly recognized as a strong predictor of bvFTD. The total number of neurons in this region, rather than the density of neurons, is associated with mood disturbance in other dementias, although there are no data on the extent and magnitude of neuronal loss in patients with bvFTD. While the density of small populations of neurons in this region has been assessed, it is unlikely that the degree of atrophy of the cingulate cortex seen in bvFTD can be explained by the loss of these subpopulations. This suggests that there is more generalized degeneration of neurons in this region in bvFTD.

The present study assesses total neuronal number, as well as characteristic pathologies, in the anterior and posterior cingulate cortices of pathologically confirmed bvFTD (N = 11) and AD (N = 9) patients compared with age-matched controls (N = 14). The bvFTD cohort comprised 5 cases with tau pathology (Pick’s disease), and 6 with TDP-43 pathology.

Results

At postmortem, atrophy was detected in the anterior and posterior cingulate cortices of bvFTD cases, but only in the posterior cingulate cortex of AD cases. As predicted, there was a significant reduction in both the density and total number of neurons in the anterior but not the posterior cingulate cortex of bvFTD cases with the opposite observed for the AD cases. Importantly, neuronal loss in the anterior cingulate cortex was only observed in cases with tau pathology.

Conclusions

This study confirms significant neuronal loss in the posterior but not anterior cingulate cortex in AD, and demonstrates that significant neuron loss in bvFTD occurs only in the anterior cingulate cortex but only in cases with tau pathology compared with cases with TDP pathology. We propose that significant neurodegeneration in the anterior cingulate cortex may be useful in differentiating the pathological subtypes in vivo.

Keywords:
Anterior cingulate cortex; Posterior cingulate cortex; Behavioral variant frontotemporal dementia; Alzheimer’s disease; Tau; TDP-43