The cell-intrinsic capacity of neurons to regenerate axons requires widespread coordination of the transcriptome, activation of multiple kinases, and reorganization of the cytoskeleton. Axonal repair Show more
The cell-intrinsic capacity of neurons to regenerate axons requires widespread coordination of the transcriptome, activation of multiple kinases, and reorganization of the cytoskeleton. Axonal repair is also influenced by extrinsic activating factors, such as neurotrophins. Here, we found that the neurotrophin BDNF amplifies multiple neuron-intrinsic programs to foster axonal regeneration in human iPSC-derived lower motor neurons (i Show less
Mild cognitive impairment (MCI) is an intermediate stage between normal and pathological brain aging, with 30% to 50% progressing to dementia within 3 to 5 years. Early identification of individuals a Show more
Mild cognitive impairment (MCI) is an intermediate stage between normal and pathological brain aging, with 30% to 50% progressing to dementia within 3 to 5 years. Early identification of individuals at high risk of progression is crucial for public health strategies. The INTERCEPTOR project included 398 MCI individuals. Baseline assessment included harmonized procedures for sociodemographic, clinical, neuropsychological, genetic (apolipoprotein E), cerebrospinal fluid (amyloid beta tau), electroencephalogram (brain connectivity), magnetic resonance imaging (hippocampal volumetry), and fluorodeoxyglucose positron emission tomography. The baseline and follow-up were completed by 351 individuals with MCI with neuropsychological tests every 6 months for 3 years. Dementia developed in 104 individuals (29.6%), including 85 (22.4%) who met core clinical criteria for probable and possible Alzheimer's disease dementia. A Cox model combining clinical and sociodemographic data achieved a concordance index of 72%, which increased to 82% when neuropsychology and biomarkers were added. The INTERCEPTOR nomogram represents a tool for predicting dementia progression risk, supporting public health strategies, including screening for risk assessment and risk/benefit ratio in innovative treatments. Show less
Cluster headache (CH) is characterized by severe, recurrent, unilateral attacks of extreme intensity and brief duration. Variants in a myriad of genes were studied in sporadic CH patients, often with Show more
Cluster headache (CH) is characterized by severe, recurrent, unilateral attacks of extreme intensity and brief duration. Variants in a myriad of genes were studied in sporadic CH patients, often with conflicting results. We studied gene mutations in some candidate genes, hypocretin receptor 2, Clock, and alcohol dehydrogenase 4 (ADH4), in 54 unrelated sporadic CH patients and in 200 controls in 8 kindreds/families that included more affected and nonaffected cases. Furthermore, we performed the whole-genome scanning by comparative genomic hybridization, searching for rearrangements associated with DNA gain or loss in a subset of sporadic and familial CH and control participants. The analysis of candidate genes revealed that only allele and genotype frequency of the 2 ADH4 mutations resulted significantly between sporadic CH and controls; the same mutations were homozygous in CH patients from 2 families. The comparative genomic hybridization analysis revealed 2 novel rearrangements that involved the intron regions of thyrotropin-releasing hormone-degrading enzyme and neurexin 3 (NRXN3) genes, respectively. The first arrangement was present either in CH or in controls, whereas the second one was specifically found in some sporadic and familial CH cases. Our data (although obtained on a small number of cases) confirm the genetic heterogeneity of CH, suggesting that mutations in the ADH4 gene and a novel rearrangement involving NRXN3 gene might be related to CH in a subset of cases. Show less