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Old age amyotrophic lateral sclerosis and limbic TDP‐43 pathology
Author(s) -
Murakami Aya,
Koga Shunsuke,
Sekiya Hiroaki,
Oskarsson Björn,
Boylan Kevin,
Petrucelli Leonard,
Josephs Keith A.,
Dickson Dennis W.
Publication year - 2022
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.13100
Subject(s) - amyotrophic lateral sclerosis , subiculum , entorhinal cortex , middle frontal gyrus , hippocampus , hippocampal sclerosis , medicine , dentate gyrus , amygdala , limbic system , pathology , temporal lobe , psychology , neuroscience , disease , central nervous system , cognition , epilepsy
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 immunohistochemistry. 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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