Detection of TDP‐43 in Alzheimer's disease and hippocampal sclerosis
Abstract
Frontotemporal lobar degeneration with ubiquitin immunoreactive inclusions (FTLD‐U) is the most common cause of frontal lobe dementia. Recently, the TAR DNA binding protein (TDP‐43) has been described as a marker for FTLD‐U. TDP‐43 has been reported to be specific for neuronal inclusions in FTLD‐U and not other degenerative disorders such as Alzheimer's disease (AD). The reported specificity of TDP‐43 makes it possible to detect FTLD‐U in the setting of other neurodegenerative diseases. On this assumption, we determined the frequency of FTLD‐U in AD. Additionally, since FTLD‐U is often associated with hippocampal sclerosis (HpScl), a process characterized by neuronal loss in Sommer's sector of the hippocampus, we also determined the frequency of FTLD‐U in HpScl. A series of 74 AD and 20 HpScl cases were screened with TDP‐43 immunohistochemistry. Immunoreactivity for TDP‐43 was detected in 13 of 20 (65%) HpScl cases and 42 of 74 (57%) AD cases, including 33 of 44 (75%) cases of AD with HpScl and 9 of 30 (30%) cases of AD without HpScl. The specificity of TDP‐43 was assessed by double immunolabeling for tau at the light and electron microscopic level. The frequency of tau and TDP‐43 co‐localization was 13%. At the EM level TDP‐43 immunoreactivity was present in cytosolic granular material, but some tau‐positive filaments were also labeled. The results suggest that FTLD‐U occurs frequently in HpScl and AD.
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TDP-43 immunoreactive inclusions are observed in about one-half of cases with FTLD and ubiquitin inclusions with or without motor neuron disease.
“TDP-43 immunoreactive inclusions are observed in the majority of cases of HS (Figure 6) [8,28,40,64], about one-half of cases with FTLD and ubiquitin inclusions with or without motor neuron disease, most sporadic cases of amyotrophic lateral sclerosis, and commonly in cases with AD neuropathologic change [8,9] or with LBD [43], as well as other neurodegenerative diseases [48].”
From National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach (2012) · cites this paper as [8]
TDP-43 immunoreactive inclusions are observed in most sporadic cases of amyotrophic lateral sclerosis.
“TDP-43 immunoreactive inclusions are observed in the majority of cases of HS (Figure 6) [8,28,40,64], about one-half of cases with FTLD and ubiquitin inclusions with or without motor neuron disease, most sporadic cases of amyotrophic lateral sclerosis, and commonly in cases with AD neuropathologic change [8,9] or with LBD [43], as well as other neurodegenerative diseases [48].”
From National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach (2012) · cites this paper as [8]
TDP-43 immunoreactive inclusions are observed in the majority of cases of HS.
“TDP-43 immunoreactive inclusions are observed in the majority of cases of HS (Figure 6) [8,28,40,64], about one-half of cases with FTLD and ubiquitin inclusions with or without motor neuron disease, most sporadic cases of amyotrophic lateral sclerosis, and commonly in cases with AD neuropathologic change [8,9] or with LBD [43], as well as other neurodegenerative diseases [48].”
From National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach (2012) · cites this paper as [8]
TDP-43 immunoreactive inclusions are commonly observed in cases with AD neuropathologic change.
“TDP-43 immunoreactive inclusions are observed in the majority of cases of HS (Figure 6) [8,28,40,64], about one-half of cases with FTLD and ubiquitin inclusions with or without motor neuron disease, most sporadic cases of amyotrophic lateral sclerosis, and commonly in cases with AD neuropathologic change [8,9] or with LBD [43], as well as other neurodegenerative diseases [48].”
From National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach (2012) · cites this paper as [8]
- Authors
- Ortiz, C. A., Lin, W., Ahmed, Z., Zehr, C., & Dickson, D. W.
- Affiliations
- Mayo Clinic in Florida (US)
- ORCID
- Dickson, Dennis W.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2007-04
- Volume
- 21
- Issue
- 5
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W151506873
- Cited by
- 0
- References
- 0
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- TDP-43, Alzheimer's disease, hippocampal sclerosis, FTLD-U, frontotemporal lobar degeneration, diagnostic specificity, neuronal inclusions, tau pathology
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