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Hippocampal sclerosis in Lewy body disease is a TDP-43 proteinopathy similar to FTLD-TDP Type A

Acta neuropathologica, 2015-01, Vol.129 (1), p.53-64 [Peer Reviewed Journal]

Springer-Verlag Berlin Heidelberg 2014 ;COPYRIGHT 2015 Springer ;Springer-Verlag Berlin Heidelberg 2015 ;ISSN: 0001-6322 ;EISSN: 1432-0533 ;DOI: 10.1007/s00401-014-1358-z ;PMID: 25367383

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Title:
Hippocampal sclerosis in Lewy body disease is a TDP-43 proteinopathy similar to FTLD-TDP Type A
Author: Aoki, Naoya ; Murray, Melissa E. ; Ogaki, Kotaro ; Fujioka, Shinsuke ; Rutherford, Nicola J. ; Rademakers, Rosa ; Ross, Owen A. ; Dickson, Dennis W.
Subjects: Aged ; Aged, 80 and over ; Alzheimer's disease ; Apolipoprotein E4 - genetics ; DNA-Binding Proteins - metabolism ; Female ; Frontotemporal Lobar Degeneration - epidemiology ; Frontotemporal Lobar Degeneration - genetics ; Frontotemporal Lobar Degeneration - metabolism ; Frontotemporal Lobar Degeneration - pathology ; Hippocampus - metabolism ; Hippocampus - pathology ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins - genetics ; Lewy body disease ; Lewy Body Disease - epidemiology ; Lewy Body Disease - genetics ; Lewy Body Disease - metabolism ; Lewy Body Disease - pathology ; Male ; Medicine ; Medicine & Public Health ; Membrane Proteins - genetics ; Nerve Tissue Proteins - genetics ; Neurites - metabolism ; Neurites - pathology ; Neurosciences ; Original Paper ; Pathology ; Sclerosis - epidemiology ; Sclerosis - genetics ; Sclerosis - metabolism ; TDP-43 Proteinopathies - epidemiology ; TDP-43 Proteinopathies - genetics ; TDP-43 Proteinopathies - metabolism ; TDP-43 Proteinopathies - pathology
Is Part Of: Acta neuropathologica, 2015-01, Vol.129 (1), p.53-64
Description: Hippocampal sclerosis (HpScl) is frequent in frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP), but it also occurs in dementia of the elderly with or without accompanying Alzheimer type pathology. HpScl has been hypothesized to be a neurodegenerative process given its association with TDP-43 pathology, but this is still controversial. TDP-43 pathology is found in Lewy body disease (LBD), but no study has focused on the pathologic and genetic characteristics of HpScl in LBD. We found HpScl in 5.2 % of 669 LBD cases (289 transitional and 380 diffuse). Older age, higher Braak neurofibrillary tangle (NFT) stage, and presence of TDP-43 pathology were associated with HpScl. There was no difference in the frequency of HpScl between transitional and diffuse LBD, suggesting that Lewy-related pathology appears to have no direct association with HpScl. All HpScl cases had TDP-43 pathology consistent with Type A pattern. HpScl cases harbored genetic variation in TMEM106B that has been previously associated with FTLD-TDP. Interestingly, the severity of TDP-43-positive fine neurites in CA1 sector, a possible pathologic precursor of HpScl, was associated with the TMEM106B variant. These results demonstrate HpScl in LBD is a TDP-43 proteinopathy and is similar to FTLD-TDP Type A. Furthermore, a subset of LBD cases without HpScl (“pre-HpScl”) had similar pathologic and genetic characteristics to typical HpScl, suggesting that the spectrum of HpScl pathology may be wider than previously thought. Some cases with many extracellular NFTs also had a similar profile. We suggest that HpScl is “masked” in these cases.
Publisher: Berlin/Heidelberg: Springer Berlin Heidelberg
Language: English
Identifier: ISSN: 0001-6322
EISSN: 1432-0533
DOI: 10.1007/s00401-014-1358-z
PMID: 25367383
Source: ProQuest One Psychology
MEDLINE
ProQuest Central

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Hippocampal sclerosis in Lewy body disease is a TDP-43 proteinopathy similar to FTLD-TDP Type A

Springer-Verlag Berlin Heidelberg 2014 ;COPYRIGHT 2015 Springer ;Springer-Verlag Berlin Heidelberg 2015 ;ISSN: 0001-6322 ;EISSN: 1432-0533 ;DOI: 10.1007/s00401-014-1358-z ;PMID: 25367383

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