TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease
Article first published online: 27 APR 2007
Copyright © 2007 American Neurological Association
Annals of Neurology
Volume 61, Issue 5, pages 435–445, May 2007
How to Cite
Amador-Ortiz, C., Lin, W.-L., Ahmed, Z., Personett, D., Davies, P., Duara, R., Graff-Radford, N. R., Hutton, M. L. and Dickson, D. W. (2007), TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease. Ann Neurol., 61: 435–445. doi: 10.1002/ana.21154
- Issue published online: 27 APR 2007
- Article first published online: 27 APR 2007
- Manuscript Accepted: 9 APR 2007
- Manuscript Revised: 28 MAR 2007
- Manuscript Received: 16 JAN 2007
- NIH (NIA). Grant Numbers: P50-AG25711, P50-AG16574, P01-AG17216, P01-AG03949, P50-NS40256
- State of Florida Department of Elder Affairs
This study aimed to determine the frequency of frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) in the setting of hippocampal sclerosis (HpScl) and Alzheimer's disease (AD) using immunohistochemistry for TAR DNA binding protein 43 (TDP-43), a putative marker for FTLD-U.
Initially, 21 cases of HpScl associated with a variety of other pathological processes and 74 cases of AD were screened for FTLD-U with TDP-43 immunohistochemistry. A confirmation study was performed on 93 additional AD cases. Specificity of TDP-43 antibodies was assessed using double-immunolabeling confocal microscopy, immunoelectron microscopy, and biochemistry.
TDP-43 immunoreactivity was detected in 71% of HpScl and 23% of AD cases. Double immunostaining of AD cases for TDP-43 and phospho-tau showed that the TDP-43–immunoreactive inclusions were usually distinct from neurofibrillary tangles. At the ultrastructural level, TDP-43 immunoreactivity in AD was associated with granular and filamentous cytosolic material and only occasionally associated with tau filaments. Western blots of AD cases showed a band that migrated at a higher molecular weight than normal TDP-43 that was not present in AD cases without TDP-43 immunoreactivity.
These results suggest that as many as 20% of AD cases and more than 70% of HpScl cases have pathology similar to that found in FTLD-U. Whether this represents concomitant FTLD-U or is analogous to colocalization of α-synuclein and tau in AD, reflecting a propensity for codeposition of abnormal protein conformers, remains to be determined. Ann Neurol 2007;61:435–445