Laminar distribution of the pathological changes in sporadic frontotemporal lobar degeneration with transactive response (TAR) DNA-binding protein of 43kDa (TDP-43) proteinopathy: a quantitative study using polynomial curve fitting

被引:7
作者
Armstrong, R. A. [1 ]
Hamilton, R. L. [3 ]
Mackenzie, I. R. A. [2 ]
Hedreen, J. [4 ,5 ]
Cairns, N. J. [6 ,7 ,8 ]
机构
[1] Aston Univ, Vis Sci, Birmingham B4 7ET, W Midlands, England
[2] Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada
[3] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA
[4] McLean Hosp, Belmont, MA 02178 USA
[5] Harvard Brain Tissue Resource Ctr, Belmont, MA USA
[6] Washington Univ, Sch Med, Charles F & Joanne Knight Alzheimers Dis Res Ctr, St Louis, MO USA
[7] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA
[8] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA
基金
美国国家卫生研究院;
关键词
frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP); FTLD with ubiquitin-positive inclusions (FTLD-U); laminar distribution; neuronal cytoplasmic inclusions (NCI); transactive response (TAR) DNA-binding protein of 43kDa (TDP-43); UBIQUITIN-POSITIVE INCLUSIONS; MOTOR-NEURON DISEASE; CREUTZFELDT-JAKOB-DISEASE; PROGRESSIVE SUPRANUCLEAR PALSY; AMYOTROPHIC-LATERAL-SCLEROSIS; ALPHA-B-CRYSTALLIN; ALZHEIMERS-DISEASE; CORTICOBASAL DEGENERATION; NEUROPATHOLOGIC ASSESSMENT; NEUROFIBRILLARY TANGLES;
D O I
10.1111/j.1365-2990.2012.01291.x
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
R. A. Armstrong, R. L. Hamilton, I. R. A. Mackenzie, J. Hedreen and N. J. Cairns (2013) Neuropathology and Applied Neurobiology39, 335347 Laminar distribution of the pathological changes in sporadic frontotemporal lobar degeneration with transactive response (TAR) DNA-binding protein of 43kDa (TDP-43) proteinopathy: a quantitative study using polynomial curve fitting Aims: Previous data suggest heterogeneity in laminar distribution of the pathology in the molecular disorder frontotemporal lobar degeneration (FTLD) with transactive response (TAR) DNA-binding protein of 43kDa (TDP-43) proteinopathy (FTLD-TDP). To study this heterogeneity, we quantified the changes in density across the cortical laminae of neuronal cytoplasmic inclusions, glial inclusions, neuronal intranuclear inclusions, dystrophic neurites, surviving neurones, abnormally enlarged neurones, and vacuoles in regions of the frontal and temporal lobe. Methods: Changes in density of histological features across cortical gyri were studied in 10 sporadic cases of FTLD-TDP using quantitative methods and polynomial curve fitting. Results: Our data suggest that laminar neuropathology in sporadic FTLD-TDP is highly variable. Most commonly, neuronal cytoplasmic inclusions, dystrophic neurites and vacuolation were abundant in the upper laminae and glial inclusions, neuronal intranuclear inclusions, abnormally enlarged neurones, and glial cell nuclei in the lower laminae. TDP-43-immunoreactive inclusions affected more of the cortical profile in longer duration cases; their distribution varied with disease subtype, but was unrelated to Braak tangle score. Different TDP-43-immunoreactive inclusions were not spatially correlated. Conclusions: Laminar distribution of pathological features in 10 sporadic cases of FTLD-TDP is heterogeneous and may be accounted for, in part, by disease subtype and disease duration. In addition, the feedforward and feedback cortico-cortical connections may be compromised in FTLD-TDP.
引用
收藏
页码:335 / 347
页数:13
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