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Κυριακή 19 Ιουνίου 2022

Old age amyotrophic lateral sclerosis and limbic TDP‐43 pathology

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Old age amyotrophic lateral sclerosis and limbic TDP-43 pathology

Regional pTDP-43 lesion burden in young-ALS and old-ALS box plots shows regional TDP-43 burden in young-, middle-, and old-ALS. The line in box plots represents the median. Old-ALS cases had greater TDP-43 burden in amygdala (p < 0.001), dentate gyrus (p < 0.05), CA1 (p < 0.01), subiculum (p < 0.01), and entorhinal cortex (p < 0.01) compared with young-ALS and middle-ALS. There is no difference between the three groups in the middle frontal cortex and white matter of the parahippocampal gyrus. ***p < 0.001, **p < 0.05, *p < 0.01. p Values are from one-way ANOVA


Abstract

This study aimed to assess and compare the burden of transactive response DNA-binding protein of 43 kDa (TDP-43) pathology and clinical features of amyotrophic lateral sclerosis (ALS) in three age groups. All cases were from the Mayo Clinic brain bank for neurodegenerative disorders and most were followed longitudinally in the ALS Clinic. Cases with moderate-to-severe Alzheimer's disease neuropathological change were excluded. The 55 cases included in the study were divided into three groups by age at death: 75 years or older (old-ALS, n = 8), 64–74 years (middle-ALS, n = 23), and 63 years or younger (young-ALS, n = 24). Clinical features, including disease duration, initial symptoms, and ALS Cognitive Behavior Score (ALS-CBS), were summarized. Sections of paraffin-embedded tissue from the motor cortex, basal forebrain, medial temporal lobe, and middle frontal gyrus were processed for phospho-TDP-43 immunohistochemist ry. The burden of TDP-43 pathology was analyzed using digital image analysis. The TDP-43 burden in the limbic system (i.e., amygdala, dentate gyrus and CA1 sector of the hippocampus, subiculum, and entorhinal cortex) was greater in old-ALS than in young-ALS and middle-ALS. TDP-43 burden in the middle frontal gyrus was sparse and did not differ between the three groups. The average of ALS-CBS was not different between the three groups. The present study shows that the amygdala and hippocampus are vulnerable to TDP-43 pathology in older patients with ALS. We discuss the evidence for and against this pathology being related to concurrent limbic-predominant, age-related TDP-43 encephalopathy neuropathologic change.

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