2015
DOI: 10.1016/j.ncl.2015.07.012
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Neuropathology of Amyotrophic Lateral Sclerosis and Its Variants

Abstract: Summary Amyotrophic lateral sclerosis (ALS) is a clinical syndrome named for its neuropathological hallmark: degeneration of motor neurons in the spinal anterior horn and motor cortex and loss of axons in the lateral columns of the spinal cord. The signature neuropathological molecular signature common to almost all sporadic ALS and most familial ALS is TDP-43 immunoreactive neuronal cytoplasmic inclusions. The neuropathological and molecular neuropathological features of ALS variants primarly lateral sclerosi… Show more

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Cited by 228 publications
(197 citation statements)
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References 147 publications
(156 reference statements)
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“…The pathology of sporadic amyotrophic lateral sclerosis (sALS) is associated with the dysregulation of the 43-kDa transactive response DNA-binding protein (TDP-43) [3, 4, 37, 49, 54, 66] that leads to the formation of proteinaceous cytoplasmic aggregates in specific cortical and subcortical projection neurons with long axons, whereas cells with short axons are spared [27, 60]. The Betz giant pyramidal cells in layer Vb of the primary neocortical motor cortex [14] and the α -motoneurons of the lower brainstem and spinal cord belong to the cell types that develop TDP-43 pathology early in the disease process [13].…”
Section: Introductionmentioning
confidence: 99%
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“…The pathology of sporadic amyotrophic lateral sclerosis (sALS) is associated with the dysregulation of the 43-kDa transactive response DNA-binding protein (TDP-43) [3, 4, 37, 49, 54, 66] that leads to the formation of proteinaceous cytoplasmic aggregates in specific cortical and subcortical projection neurons with long axons, whereas cells with short axons are spared [27, 60]. The Betz giant pyramidal cells in layer Vb of the primary neocortical motor cortex [14] and the α -motoneurons of the lower brainstem and spinal cord belong to the cell types that develop TDP-43 pathology early in the disease process [13].…”
Section: Introductionmentioning
confidence: 99%
“…Furthermore, the factors initiating the dysregulation of intranuclear TDP-43 are not known. Use of antibodies directed against the native protein shows that in neuronal types susceptible to sALS a reduction or absence of normal nuclear TDP-43 immunoreactivity is associated with TDP-43 mislocalization and inclusion body formation [28, 54, 66]. During its cytoplasmic phase, the protein becomes abnormally phosphorylated (pTDP-43) and possibly undergoes a conformational change [34, 41, 55, 69].…”
Section: Introductionmentioning
confidence: 99%
“…8,9 On a pathological level, it is well established that TDP-43 is the main pathology found in most of ALS cases. [10][11][12][13] Interestingly, TDP-43 is also one of the main pathologies (~50%) of FTD, in particular in SD as it accounts for 75% of the cases. 14 Although there are different subtypes of TDP-43 depositions, the presence of a shared proteinopathy reinforces the idea of a continuum across ALS and FTD.…”
Section: Introductionmentioning
confidence: 99%
“…These are considered to be the pathological hallmark of ALS (Okamoto, Mizuno et al 2008), along with the accumulation of insoluble protein aggregates (Peters, Ghasemi et al , Leigh, Anderton et al 1988, Okamoto, Mizuno et al 2008. The pathological protein aggregations vary among patients and can be categorized into TAR DNA-binding protein (Tdp-43) pathology, Tdp-with C9orf72 pathology, FUS pathology, and superoxide dismutase gene (SOD1) pathology (Saberi, Stauffer et al 2015).…”
Section: List Of Supplementary Tablesmentioning
confidence: 99%