In recent years, large scale meta-analysis of genome-wide association studies (GWAS) have reliably identified genetic polymorphisms associated with neuropsychiatric disorders such as schizophrenia (SCZ), bipolar disorder (BPD) and major depressive disorder (MDD). However, the majority of disease-associated single nucleotide polymorphisms (SNPs) appear within functionally ambiguous non-coding genomic regions. Recently, increased emphasis has been placed on identifying the functional relevance of disease-associated variants via correlating risk polymorphisms with gene expression levels in etiologically relevant tissues. For neuropsychiatric disorders, the etiologically relevant tissue is brain, which requires robust postmortem sample sizes from varying genetic backgrounds. While small sample sizes are of decreasing concern, postmortem brain databases are composed almost exclusively of Caucasian samples, which significantly limits study design and result interpretation. In this review, we highlight the importance of gene expression and expression quantitative loci (eQTL) studies in clinically relevant postmortem tissue while addressing the current limitations of existing postmortem brain databases. Finally, we introduce future collaborations to develop postmortem brain databases for neuropsychiatric disorders from Chinese and Asian subpopulations.
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http://dx.doi.org/10.1016/j.neubiorev.2019.04.015 | DOI Listing |
Mol Cell Biochem
January 2025
Neurodegenerative Diseases Laboratory, Center for Biomedicine, Universidad Mayor, Avenida Alemania 0281, 4780000, Temuco, La Araucanía, Chile.
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by tremor, rigidity, and bradykinesia, beginning with early loss of dopaminergic neurons in the ventrolateral substantia nigra and advancing to broader neurodegeneration in the midbrain. The clinical heterogeneity of PD and the lack of specific diagnostic tests present significant challenges, highlighting the need for reliable biomarkers for early diagnosis. Alpha-synuclein (α-Syn), a protein aggregating into Lewy bodies and neurites in PD patients, has emerged as a key biomarker due to its central role in PD pathophysiology and potential to reflect pathological processes.
View Article and Find Full Text PDFGlia
January 2025
Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA.
Human genetics studies lent firm evidence that microglia are key to Alzheimer's disease (AD) pathogenesis over a decade ago following the identification of AD-associated genes that are expressed in a microglia-specific manner. However, while alterations in microglial morphology and gene expression are observed in human postmortem brain tissue, the mechanisms by which microglia drive and contribute to AD pathology remain ill-defined. Numerous mouse models have been developed to facilitate the disambiguation of the biological mechanisms underlying AD, incorporating amyloidosis, phosphorylated tau, or both.
View Article and Find Full Text PDFLancet Reg Health Eur
February 2025
Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, the Netherlands.
Background: Intracerebral haemorrhage (ICH) accounts for approximately 28% of all strokes worldwide. ICH has a high case fatality, and only few survivors recover to independent living. Over the past decades, demographic changes, and changes in prevalence and management of risk factors may have influenced incidence.
View Article and Find Full Text PDFNeurobiol Pain
December 2024
School of Medical Sciences [Neuroscience], and the Brain & Mind Centre, The University of Sydney, NSW, 2006, Australia.
Chronic neuropathic pain is a debilitating condition that results from damage to the nervous system. Current treatments are largely ineffective, with limited understanding of the underlying mechanisms hindering development of effective treatments. Preclinical models of neuropathic pain have revealed that non-neural changes are important for the development of neuropathic pain, although these data are derived almost exclusively from post-mortem histological analyses.
View Article and Find Full Text PDFOne Health Outlook
January 2025
Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, São Paulo, SP, Brazil.
Background: Rabies, a lethal viral zoonotic disease, remains a significant global public health concern. In northeastern Brazil, in particular, its epidemiology is complex and dynamic, characterized by the presence of several reservoirs associated with human rabies infection.
Methods: This study, conducted from June 2022 to July 2023, was part of a passive epidemiological surveillance initiative under Brazil's National Rabies Surveillance Program.
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