6 research outputs found
Gene expression profiling of the dorsolateral and medial orbitofrontal cortex in schizophrenia
Schizophrenia is a complex polygenic disorder of unknown etiology. Over 3,000 candidate genes associated with schizophrenia have been reported, most of which being mentioned only once. Alterations in cognitive processing - working memory, metacognition and mentalization - represent a core feature of schizophrenia, which indicates the involvement of the prefrontal cortex in the pathophysiology of this disorder. Hence we compared the gene expression in postmortem tissue from the left and right dorsolateral prefrontal cortex (DLPFC, Brodmann's area 46), and the medial part of the orbitofrontal cortex (MOFC, Brodmann's area 11/12), in six patients with schizophrenia and six control brains. Although in the past decade several studies performed transcriptome profiling in schizophrenia, this is the first study to investigate both hemispheres, providing new knowledge about possible brain asymmetry at the level of gene expression and its relation to schizophrenia. We found that in the left hemisphere, twelve genes from the DLPFC and eight genes from the MOFC were differentially expressed in patients with schizophrenia compared to controls. In the right hemisphere there was only one gene differentially expressed in the MOFC. We reproduce the involvement of previously reported genes TARDBP and HNRNPC in the pathogenesis of schizophrenia, and report seven novel genes: SART1, KAT7, C1D, NPM1, EVI2A, XGY2, and TTTY15. As the differentially expressed genes only partially overlap with previous studies that analyzed other brain regions, our findings indicate the importance of considering prefrontal cortical regions, especially those in the left hemisphere, for obtaining disease-relevant insights
Monoaminergic Neuropathology in Alzheimer's disease
Acknowledgments This work was supported by The Croatian Science Foundation grant. no. IP-2014-09-9730 (āTau protein hyperphosphorylation, aggregation, and trans-synaptic transfer in Alzheimerās disease: cerebrospinal fluid analysis and assessment of potential neuroprotective compoundsā) and European Cooperation in Science and Technology (COST) Action CM1103 (āStucture-based drug design for diagnosis and treatment of neurological diseases: dissecting and modulating complex function in the monoaminergic systems of the brainā). PRH is supported in part by NIH grant P50 AG005138.Peer reviewedPostprin
Association of MAPT haplotypeātagging polymorphisms with cerebrospinal fluid biomarkers of Alzheimer's disease: A preliminary study in a Croatian cohort
Introduction:
Alzheimer's disease (AD) is the world leading cause of dementia. Early detection of AD is essential for faster and more efficacious usage of therapeutics and preventive measures. Even though it is well known that one Īµ4 allele of apolipoprotein E gene increases the risk for sporadic AD five times, and that two Īµ4 alleles increase the risk 20 times, reliable genetic markers for AD are not yet available. Previous studies have shown that microtubuleāassociated protein tau (MAPT) gene polymorphisms could be associated with increased risk for AD.
Methods:
The present study included 113 AD patients and 53 patients with mild cognitive impairment (MCI), as well as nine healthy controls (HC) and 53 patients with other primary causes of dementia. The study assessed whether six MAPT haplotypeātagging polymorphisms (rs1467967, rs242557, rs3785883, rs2471738, delāIn9, and rs7521) and MAPT haplotypes are associated with AD pathology, as measured by cerebrospinal fluid (CSF) AD biomarkers amyloid Ī²1ā42 (AĪ²1ā42), total tau (tātau), tau phosphorylated at epitopes 181 (pātau181), 199 (pātau199), and 231 (pātau231), and visininālike protein 1 (VILIPā1).
Results:
Significant increases in tātau and pātau CSF levels were found in patients with AG and AA MAPT rs1467967 genotype, CC MAPT rs2471738 genotype and in patients with H1H2 or H2H2 MAPT haplotype.
Conclusions:
These results indicate that MAPT haplotypeātagging polymorphisms and MAPT haplotypes should be further tested as potential genetic biomarkers of AD