GWAS linksAPOEto neuropsychiatric symptoms in mild cognitive impairment and dementia DOI Creative Commons
Selina Vattathil, Freida Blostein, Tyne W. Miller‐Fleming

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 2, 2025

Abstract INTRODUCTION Neuropsychiatric symptoms in dementia (NPS) collectively refer to behavioral and psychological affecting individuals with mild cognitive impairment (MCI) or Alzheimer’s disease related (ADRD). NPS are among the most troubling aspects of living their treatments have limited efficacy. We aim investigate genetic variants contributing identify new therapeutic targets. METHODS performed a genome-wide association study (GWAS) for nine domains measured by NPI-Q 12,800 participants European ancestry MCI ADRD recruited research centers across U.S. RESULTS found significant signals agitation, anxiety, apathy, delusions, hallucinations APOE locus that were driven ε4 allele. replicated these findings two independent datasets. Mediation analyses revealed MCI/ADRD severity only partially mediated GWAS signals, except apathy. DISCUSSION These suggest allele influences independently beyond its effect on ADRD.

Language: Английский

Modern Methods of Diagnostics and Treatment of Neurodegenerative Diseases and Depression DOI Creative Commons
Natalia Shusharina, Denis Yukhnenko, Stepan Botman

et al.

Diagnostics, Journal Year: 2023, Volume and Issue: 13(3), P. 573 - 573

Published: Feb. 3, 2023

This paper discusses the promising areas of research into machine learning applications for prevention and correction neurodegenerative depressive disorders. These two groups disorders are among leading causes decline in quality life world when estimated using disability-adjusted years. Despite decades research, development new approaches assessment (especially pre-clinical) diseases remains priority neurophysiology, psychology, genetics, interdisciplinary medicine. Contemporary technologies medical data infrastructure create opportunities. However, reaching a consensus on application methods their integration with existing standards care is still challenge to overcome before innovations could be widely introduced clinics. The clinical predictions classification algorithms contributes towards creating unified approach use growing data. should integrate requirements professionals, researchers, governmental regulators. In current paper, state presented.

Language: Английский

Citations

56
Ketogenic Diet Intervention on Metabolic and Psychiatric Health in Bipolar and Schizophrenia: A Pilot Trial DOI Creative Commons
Shebani Sethi, Diane E. Wakeham, Terence A. Ketter

et al.

Psychiatry Research, Journal Year: 2024, Volume and Issue: 335, P. 115866 - 115866

Published: March 20, 2024

The ketogenic diet (KD, also known as metabolic therapy) has been successful in the treatment of obesity, type 2 diabetes, and epilepsy. More recently, this shown promise psychiatric illness. We conducted a 4–month pilot study to investigate effects KD on individuals with schizophrenia or bipolar disorder existing abnormalities. Twenty–three participants were enrolled single–arm trial. Results showcased improvements health, no meeting syndrome criteria by conclusion. Adherent experienced significant reduction weight (12%), BMI waist circumference (13%), visceral adipose tissue (36%). Observed biomarker enhancements population include 27% decrease HOMA–IR, 25% drop triglyceride levels. In measurements, showed 32% Brief Psychiatric Rating Scale scores. Overall Clinical Global Impression (CGI) severity improved an average 31%, proportion that started elevated symptomatology at least 1–point CGI (79%). outcomes across cohort encompassed increased life satisfaction (17%) enhanced sleep quality (19%). This trial underscores potential advantages adjunctive dietary grappling serious mental

Language: Английский

Citations

50
Shared genetic risk loci between Alzheimer’s disease and related dementias, Parkinson’s disease, and amyotrophic lateral sclerosis DOI Creative Commons
Michael Wainberg, Shea J. Andrews, Shreejoy J. Tripathy

et al.

Alzheimer s Research & Therapy, Journal Year: 2023, Volume and Issue: 15(1)

Published: June 16, 2023

Genome-wide association studies (GWAS) have indicated moderate genetic overlap between Alzheimer's disease (AD) and related dementias (ADRD), Parkinson's (PD) amyotrophic lateral sclerosis (ALS), neurodegenerative disorders traditionally considered etiologically distinct. However, the specific variants loci underlying this remain almost entirely unknown.

Language: Английский

Citations

47
Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood DOI
Nikolaos P. Daskalakis, Artemis Iatrou, Chris Chatzinakos

et al.

Science, Journal Year: 2024, Volume and Issue: 384(6698)

Published: May 23, 2024

The molecular pathology of stress-related disorders remains elusive. Our brain multiregion, multiomic study posttraumatic stress disorder (PTSD) and major depressive (MDD) included the central nucleus amygdala, hippocampal dentate gyrus, medial prefrontal cortex (mPFC). Genes exons within mPFC carried most disease signals replicated across two independent cohorts. Pathways pointed to immune function, neuronal synaptic regulation, hormones. Multiomic factor gene network analyses provided underlying genomic structure. Single RNA sequencing in dorsolateral PFC revealed dysregulated (stress-related) non-neuronal cell types. Analyses brain-blood intersections >50,000 UK Biobank participants were conducted along with fine-mapping results PTSD MDD genome-wide association studies distinguish risk from processes. data suggest shared distinct both propose potential therapeutic targets biomarkers.

Language: Английский

Citations

22
RNA dysregulation in neurodegenerative diseases DOI Creative Commons
Yini Li, Shuying Sun

The EMBO Journal, Journal Year: 2025, Volume and Issue: 44(3), P. 613 - 638

Published: Jan. 9, 2025

Dysregulation of RNA processing has in recent years emerged as a significant contributor to neurodegeneration. The diverse mechanisms and molecular functions underlying underscore the essential role regulation maintaining neuronal health function. molecules are bound by RNA-binding proteins (RBPs), interactions between RNAs RBPs commonly affected In this review, we highlight progress understanding dysregulated RNA-processing pathways causes RBP dysfunction across various neurodegenerative diseases. We discuss both established emerging RNA-mediated neuropathogenesis rapidly evolving field. Furthermore, explore development potential RNA-targeting therapeutic approaches for treatment

Language: Английский

Citations

3
Sex differences in brain protein expression and disease DOI Creative Commons
Aliza P. Wingo, Yue Liu, Ekaterina S. Gerasimov

et al.

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(9), P. 2224 - 2232

Published: Aug. 31, 2023

Abstract Most complex human traits differ by sex, but we have limited insight into the underlying mechanisms. Here, investigated influence of biological sex on protein expression and its genetic regulation in 1,277 brain proteomes. We found that 13.2% (1,354) proteins had sex-differentiated abundance 1.5% (150) sex-biased quantitative trait loci (sb-pQTLs). Among genes with expression, 67% concordance between transcript levels; however, effects were more evident at level. Considering 24 psychiatric, neurologic morphologic traits, an average 25% their putatively causal 12 sb-pQTLs. Furthermore, integrating sex-specific pQTLs sex-stratified genome-wide association studies six psychiatric conditions, uncovered another 23 contributing to these one not other. Together, findings begin provide insights mechanisms differences disease.

Language: Английский

Citations

39
Depression in Alzheimer’s Disease: Epidemiology, Mechanisms, and Treatment DOI
Yu‐Yuan Huang,

Yi‐Han Gan,

Yang Liu

et al.

Biological Psychiatry, Journal Year: 2023, Volume and Issue: 95(11), P. 992 - 1005

Published: Oct. 20, 2023

Language: Английский

Citations

34
TSPO PET brain inflammation imaging: A transdiagnostic systematic review and meta-analysis of 156 case-control studies DOI Creative Commons
Livia De Picker, Manuel Morrens, Igor Branchi

et al.

Brain Behavior and Immunity, Journal Year: 2023, Volume and Issue: 113, P. 415 - 431

Published: Aug. 3, 2023

The 18-kDa translocator protein (TSPO) is increasingly recognized as a molecular target for PET imaging of inflammatory responses in various central nervous system (CNS) disorders. However, the reported sensitivity and specificity TSPO to identify brain processes appears vary greatly across disorders, disease stages, applied quantification methods. To advance potential biomarker evaluate inflammation anti-inflammatory therapies, better understanding its applicability disorders needed. We conducted transdiagnostic systematic review meta-analysis all vivo human case-control studies CNS. Specifically, we investigated direction, strength, heterogeneity associated with signal pre-specified regions, explored demographic methodological sources heterogeneity.We searched English peer-reviewed articles that differences. extracted details, outcomes, technical variables procedure. A random-effects was estimate standardized mean differences (SMD) lobar/whole-brain cortical grey matter (cGM), thalamus, cortico-limbic circuitry between different illness categories. Heterogeneity evaluated I2 statistic using subgroup meta-regression analyses radioligand generation, method, age, sex, publication year. Significance set at False Discovery Rate (FDR)-corrected P < 0.05.156 individual were included review, incorporating data 2381 healthy controls 2626 patients. 139 documented meta-analysable grouped into 11 Across categories, observed significantly higher cases compared cGM (n = 121 studies, SMD 0.358, PFDR 0.001, 68%), significant difference categories (P 0.004). increases only Alzheimer's (SMD 0.693, 64%) other neurodegenerative 0.929, 73%). Cortico-limbic 97 0.541, 67%) most prominent disease, mild cognitive impairment, mood multiple sclerosis. Thalamic involvement 79 0.393, 71%) sclerosis, chronic pain functional (all 0.05). Main outcomes systemic immunological viral infections, substance use schizophrenia traumatic injury not significant. identified between-study variance including strong effect method (explaining 25% variance; VT-based 0.000 versus reference tissue-based 0.630; F 20.49, df 1;103, 0.001), patient age (9% variance), generation (5% variance).This study first overarching findings humans several regions. robust specific types which widespread or focal depending on category. also found large horizontal (positive) shift estimates studies. Our results can support future optimize experimental design power calculations, by taking account type disorder, region-of-interest, radioligand, method.

Language: Английский

Citations

27
A multi-ancestry genetic study of pain intensity in 598,339 veterans DOI
Sylvanus Toikumo,

Rachel Vickers‐Smith,

Zeal Jinwala

et al.

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(4), P. 1075 - 1084

Published: March 1, 2024

Language: Английский

Citations

14
Distinctive whole-brain cell types predict tissue damage patterns in thirteen neurodegenerative conditions DOI Creative Commons
Veronika Pak, Quadri Adewale, Danilo Bzdok

et al.

eLife, Journal Year: 2024, Volume and Issue: 12

Published: March 21, 2024

For over a century, brain research narrative has mainly centered on neuron cells. Accordingly, most neurodegenerative studies focus neuronal dysfunction and their selective vulnerability, while we lack comprehensive analyses of other major cell types’ contribution. By unifying spatial gene expression, structural MRI, deconvolution, here describe how the human distribution canonical types extensively predicts tissue damage in 13 conditions, including early- late-onset Alzheimer’s disease, Parkinson’s dementia with Lewy bodies, amyotrophic lateral sclerosis, mutations presenilin-1, 3 clinical variants frontotemporal lobar degeneration (behavioral variant, semantic non-fluent primary progressive aphasia) along associated three-repeat four-repeat tauopathies TDP43 proteinopathies A C. We reconstructed whole-brain reference maps cellular abundance for six identified characteristic axes overlapping atrophy. Our results support strong mediating role non-neuronal cells, primarily microglia astrocytes, vulnerability to loss neurodegeneration, distinct shared across-disorder pathomechanisms. These observations provide critical insights into multicellular pathophysiology underlying spatiotemporal advance neurodegeneration. Notably, they also emphasize need exceed current neuro-centric view diseases, supporting imperative cell-specific therapeutic targets

Language: Английский

Citations

7