2021
DOI: 10.1007/s00401-021-02269-4
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Developmental malformations in Huntington disease: neuropathologic evidence of focal neuronal migration defects in a subset of adult brains

Abstract: Neuropathologic hallmarks of Huntington Disease (HD) include the progressive neurodegeneration of the striatum and the presence of Huntingtin (HTT) aggregates that result from abnormal polyQ expansion of the HTT gene. Whether the pathogenic trinucleotide repeat expansion of the HTT gene causes neurodevelopmental abnormalities has garnered attention in both murine and human studies; however, documentation of discrete malformations in autopsy brains of HD individuals has yet to be described. We retrospectively s… Show more

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Cited by 26 publications
(22 citation statements)
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References 64 publications
(79 reference statements)
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“…The 65 brains of this study had a pathologic diagnosis of HD and known HTT CAG repeat size. All brains were processed using the standardized protocol in place at the New York Brain Bank as outlined previously [ 28 , 62 ]. The half brain or whole brain that was assigned for neuropathologic diagnosis, was fixed by immersion in 10% neutral-buffered formalin solution for approximately two weeks and then cut and blocked as per the standardized New York Brain Bank protocol as previously described [ 62 ].…”
Section: Methodsmentioning
confidence: 99%
See 1 more Smart Citation
“…The 65 brains of this study had a pathologic diagnosis of HD and known HTT CAG repeat size. All brains were processed using the standardized protocol in place at the New York Brain Bank as outlined previously [ 28 , 62 ]. The half brain or whole brain that was assigned for neuropathologic diagnosis, was fixed by immersion in 10% neutral-buffered formalin solution for approximately two weeks and then cut and blocked as per the standardized New York Brain Bank protocol as previously described [ 62 ].…”
Section: Methodsmentioning
confidence: 99%
“…Hematoxylin counterstains were performed. We used the 2B4 antibody which targets amino acids 1–82 of the N-terminal end of HTT to study HTT inclusions; this antibody has been validated in human HD brains previously [ 11 , 12 , 25 , 28 ]. To corroborate the distribution of HTT, we also examined sections stained with an antibody directed against p62 in a subset of cases (n = 39).…”
Section: Methodsmentioning
confidence: 99%
“…The neurodevelopmental changes in FCD are characterized by abnormal cortical structures and heterotopias caused by disruption of neuronal migration by somatic mutations of genes that encode proteins in the PI3K-AKT/mTOR pathway (Guerrini and Barba, 2021). Heterotopias are a common feature in both the GD-15 and GD-17 MAM animal models, and these pathological changes are comparable to the individual ectopic neurons reported in the brains of Guam and Kii ALS/PDC subjects (Shiraki and Yase, 1975;Morimoto et al, 2018) and HD (Hickman et al, 2021). Additionally, genomewide association studies show that schizophrenia is associated with ALS (McLaughlin et al, 2017;Restuadi et al, 2021;Spencer and Kisby, 2021a), and diagnosis of schizophrenia prior to onset of motorsystem disease has been reported in ALS/PDC (Yase et al, 1972).…”
Section: Cycad Genotoxins and Neurodevelopmentmentioning
confidence: 76%
“…Exposure to cycad genotoxins during early human brain development might be an important driver of the ensuing pathological features of ALS/PDC, comparable to HD where a mutant gene ( Htt) perturbs neurodevelopment that results in age-related decline in cognitive function ( Ruzo et al, 2018 ; van der Plas et al, 2019 ; Barnat et al, 2020 ; Hickman et al, 2021 ; Schultz et al, 2021 ).…”
Section: Cycad Genotoxins and Neurodevelopmentmentioning
confidence: 99%
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