While we also found a remarkably high frequency of TDP-43 pathology in controls, this was restricted exclusively to the amygdala/HATA region in all cases. We suspect age may be important factor explaining the relatively low frequency of TDP-43 pathology in the presenilin mutation cases.doi:10.1016/j.jalz.2009.05.338James ...
responsible for ALS; (3) the A4V mutation is the most commonly detected of all SOD1 mutations in familial ALS, and give raise to the most aggressive form of ALS, with reduced survival time after onset (i.e., 1.2 years as compared to 2.5 years for all other familial ALS patients) [...
developing cognitive decline during the study (https://dataportal.AnswerALS.org). A small number of individuals were ALS mutation carriers (asymptomatic ALS) without overt neurological disease (Table1). Non-ALS motor neuron disease (MND) included patients with predominantly upper MND, not formally ...
recent work has suggested that injury to the NPC can at least in part contribute to TDP-43 loss of function and mislocalization, a pathological hallmark of ALS and related neurodegenerative
Fisher exact test was used to calculate the significance of rare variant accumulation in patients with ALS, with statistical significance defined as 2-sided P<.05. Mutation counts and annotations are given in Table 1 and eTable 1. Functional relevance of all mutations was analyzed in silico (e...
monitor oxidative stress; secondly, we used the Seahorse Bioscience XF Analyzer to monitor oxygen consumption rate (OCR) and the rate of extracellular acidification (ECAR), and finally we determined changes in metabolism in lymphoblasts from healthy controls and sALS and SOD1-...
Han et al. reported that a decrease in expression of neuronal vMSP, a cleavage product of VAPB, due to mutation of VAPB/ALS8 in ALS, triggers FoxO activation, increases ATP levels, and prolongs survival in VAPB C. elegans mutants56. Zhang et al. have revealed in proteotoxic stress ...
In cellular models, SOD1 mutation results in loss of mitochondrial respiration while increasing glycolytic flux42,43. These studies emphasize the importance of understanding the interplay between differentiation state and energy metabolism in the context of ALS, but such studies have not been done. ...
The role of mitochondria in the pathogenesis of amyotrophic lateral sclerosis (ALS) Ultrastructural Pathology 26(1): 1-2 Guerreiro, R.J.; Schymick, J.C.; Crews, C.; Singleton, A.; Hardy, J.; Traynor, B.J. 2008: TDP-43 is not a common cause of sporadic amyotrophic lateral sclerosis...
To date, 41 different TDP-43 pathogenic mutations (40 missense and one frameshift mutation) (Supplementary Table S1) have been reported in ALS patients of different ethnicities, mainly in White populations (Baumer et al., 2009, Benajiba et al., 2009, Chiò et al., 2010, Chiò et al., ...