NeuralCipher Research overview
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Failure of axonal maintenance is proposed as a mechanism shared by Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). We reanalysed three public post-mortem resources under one rule set: bulk RNA-seq of 1242 samples from 319 donors (GSE153960) and midbrain single-nucleus RNA-seq (GSE157783, GSE178265). As a contributing project, a second batch variable tracked diagnosis in both cord segments and was completely separated from it in three cortical regions, which we removed. Adjusting for this removed a third of the naive differential expression. In ALS cord, the dominant depleted program was microtubule-based axonal transport (normalised enrichment score -2.40, FDR p = 0.57). No GCN2 activity was measured, and the ALS cord is compared against PD midbrain. The axes that survive this control are glial and translational; the axonal question is not adjudicable in PD, where the panel score tracks dopaminergic content.
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