Sequential distribution of pTDP-43 pathology in behavioral variant frontotemporal dementia (bvFTD) View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-01-10

AUTHORS

Johannes Brettschneider, Kelly Del Tredici, David J. Irwin, Murray Grossman, John L. Robinson, Jon B. Toledo, Lubin Fang, Vivianna M. Van Deerlin, Albert C. Ludolph, Virginia M.-Y. Lee, Heiko Braak, John Q. Trojanowski

ABSTRACT

We examined regional distribution patterns of phosphorylated 43-kDa TAR DNA-binding protein (pTDP-43) intraneuronal inclusions in frontotemporal lobar degeneration (FTLD). Immunohistochemistry was performed on 70 μm sections from FTLD-TDP autopsy cases (n = 39) presenting with behavioral variant frontotemporal dementia. Two main types of cortical pTDP-43 pathology emerged, characterized by either predominantly perikaryal pTDP-43 inclusions (cytoplasmic type, cFTLD) or long aggregates in dendrites (neuritic type, nFTLD). Cortical involvement in nFTLD was extensive and frequently reached occipital areas, whereas cases with cFTLD often involved bulbar somatomotor neurons and the spinal cord. We observed four patterns indicative of potentially sequential dissemination of pTDP-43: cases with the lowest burden of pathology (pattern I) were characterized by widespread pTDP-43 lesions in the orbital gyri, gyrus rectus, and amygdala. With increasing burden of pathology (pattern II) pTDP-43 lesions emerged in the middle frontal and anterior cingulate gyrus as well as in anteromedial temporal lobe areas, the superior and medial temporal gyri, striatum, red nucleus, thalamus, and precerebellar nuclei. More advanced cases showed a third pattern (III) with involvement of the motor cortex, bulbar somatomotor neurons, and the spinal cord anterior horn, whereas cases with the highest burden of pathology (pattern IV) were characterized by pTDP-43 lesions in the visual cortex. We interpret the four neuropathological patterns in bvFTD to be consistent with the hypothesis that pTDP-43 pathology can spread sequentially and may propagate along axonal pathways. More... »

PAGES

423-439

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    http://scigraph.springernature.com/pub.10.1007/s00401-013-1238-y

    DOI

    http://dx.doi.org/10.1007/s00401-013-1238-y

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1050245217

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/24407427


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