Abstract：
:Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) can typically be categorized into one of four distinct histopathologic patterns of TDP-43 pathology, types A to D. The strength of this histopathologic classification lies in the association between FTLD-TDP subtypes and various clinical and genetic features of disease. Seven cases of FTLD-TDP were identified here which were difficult to classify based on existing pathologic criteria. Distinct features common to these cases included TDP-43 aggregates over a wide neuroanatomic distribution comprised of granulofilamentous neuronal inclusions, abundant grains, and oligodendroglial inclusions. TDP-43 aggregates were phosphorylated and associated with loss of normal nuclear TDP-43 protein (nuclear clearance) but were negative for ubiquitin. Biochemical analysis confirmed the presence of insoluble and phosphorylated TDP-43 and also revealed a distinct pattern of TDP-43 C-terminal fragments relative to other FTLD-TDP subtypes. Finally, these cases were uniformly associated with a very rapid clinical course culminating in death within ~3 years of disease onset. We suggest that these cases may represent a unique clinicopathologic subtype of FTLD-TDP which we provisionally call "type E." The immature appearance of TDP-43 aggregates, widespread distribution, uniform biochemical profile and rapid clinical course highlights the clinical and pathologic variability within FTLD-TDP, and raises the possibility that type E neuropathology is the sequelae of a particularly virulent strain of TDP-43 proteinopathy.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Lee EB,Porta S,Michael Baer G,Xu Y,Suh E,Kwong LK,Elman L,Grossman M,Lee VM,Irwin DJ,Van Deerlin VM,Trojanowski JQdoi
10.1007/s00401-017-1679-9subject
Has Abstractpub_date
2017-07-01 00:00:00pages
65-78issue
1eissn
0001-6322issn
1432-0533pii
10.1007/s00401-017-1679-9journal_volume
134pub_type
杂志文章abstract：:Acetylcholinesterase and butyrylcholinesterase have been associated with structures undergoing neurofibrillary degeneration, as well as with all types of senile plaques, in non-demented aged and Alzheimer's brains. At the electron microscope level, the reaction product of both enzymes, appeared to decorate paired heli...
journal_title：Acta neuropathologica
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journal_title：Acta neuropathologica
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