Neurobiology of aging
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Neurobiology of aging · Mar 2016
ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion.
There are indications that both familial amyotrophic lateral sclerosis (ALS) and sporadic ALS phenotype and prognosis are partly regulated by genetic and environmental factors, supporting the theory that ALS is a multifactorial disease. The aim of this article was to assess the role of ATXN2 intermediate length repeats in a large series of Italian and Sardinian ALS patients and controls carrying a pathogenetic C9ORF72 GGGGCC hexanucleotide repeat. A total of 1972 ALS cases were identified through the database of the Italian ALS Genetic consortium, a collaborative effort including 18 ALS centers throughout Italy. ⋯ Intermediate length repeat alleles were found in 12 (1.5%) Italian controls and 1 (0.84%) Sardinian controls. Therefore, ALS patients with C9ORF72 expansion showed a lower frequency of ATXN2 polyQ intermediate length repeats than both controls (Italian cases, p = 0.137; Sardinian cases, p = 0.0001) and ALS patients without C9ORF72 expansion (Italian cases, p = 0.005; Sardinian cases, p = 0.178). In our large study on Italian and Sardinian ALS patients with C9ORF72 GGGGCC hexanucleotide repeat expansion, compared to age-, gender- and ethnic-matched controls, ATXN2 polyQ intermediate length does not represent a modifier of ALS risk, differently from non-C9ORF72 mutated patients.
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Neurobiology of aging · Feb 2016
Lack of CHCHD2 mutations in Parkinson's disease in a Taiwanese population.
A recent study identified a missense mutation in coiled-coil-helix-coiled-coil-helix domain-containing 2 (CHCHD2) gene, p. Thr61Ile, in a Japanese multigenerational family with autosomal dominant Parkinson's disease (PD). Subsequent analyses identified several genetic variants in this gene that contributed to increased risk of sporadic PD, making CHCHD2 a novel candidate gene associated with PD. ⋯ However, we did not find any significant associations between p. Pro2Leu (rs142444896) and risk of PD in our study cohort (0.86% vs. 1.20%, p = 0.20). Our data suggest that genetic variants of CHCHD2 do not play a major role in our Taiwanese PD population.
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Neurobiology of aging · Feb 2016
Mutation analysis of CHCHD2 in Canadian patients with familial Parkinson's disease.
Recently, several CHCHD2 mutations were reported to be associated with autosomal dominant Parkinson's disease (PD) in a Japanese population. However, an association between CHCHD2 and PD was not observed in 2 Caucasian data sets. ⋯ Moreover, 3 coding CHCHD2 polymorphisms available on the NeuroX array (Pro2Leu, Pro14Ser, and Ile118Met) were homozygous for the major allele in an additional 85 PD patients. Our study suggests that CHCHD2 mutations may not account for PD in Canadian patients.
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Neurobiology of aging · Dec 2015
Functional connectivity change across multiple cortical networks relates to episodic memory changes in aging.
A major task of contemporary cognitive neuroscience of aging is to explain why episodic memory declines. Change in resting-state functional connectivity (rsFC) could be a mechanism accounting for reduced function. We addressed this through 3 studies. ⋯ This suggests that cognitive consequences of rsFC change are not stable across age. In study 2 and 3, the age-dependent differences in rsFC-memory relationship were replicated by use of a simulation model (study 2) and by a cross-sectional experimental recognition memory task (study 3). In conclusion, memory changes were related to altered rsFC in an age-dependent manner, and future research needs to detail the mechanisms behind age-varying relationships.
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Neurobiology of aging · Dec 2015
Meta AnalysisMotor and extra-motor gray matter atrophy in amyotrophic lateral sclerosis: quantitative meta-analyses of voxel-based morphometry studies.
Considerable evidence from previous voxel-based morphometry studies indicates widespread but heterogeneous gray matter (GM) deficits in amyotrophic lateral sclerosis (ALS). Here, we aimed to investigate the concurrence across voxel-based morphometry studies to help clarify the spatial pattern of GM abnormalities that underlie this condition. Comprehensive meta-analyses to assess regional GM anomalies in ALS were conducted with the Anisotropic Effect Size version of Signed Differential Mapping software package. ⋯ Meta-regression demonstrated that the disease duration, disease severity, and age were significantly related to GM deficits in ALS patients. The present meta-analysis provides convergent evidence that ALS is a multisystem degenerative disorder that is accompanied by a unique and widespread pattern of robust cortical GM atrophy. Future studies should investigate whether this atrophy pattern is a diagnostic and prognostic marker.