Basic Science and Pathogenesis.

Background: Positron emission tomography (PET) imaging greatly impacted Alzheimer's disease (AD) research and diagnosis. which makes predicting PET brain imaging alterations using blood data is of high interest. Additionally, integrating PET and omics data can provide new insights into AD pathophysiology.

Basic Science and Pathogenesis.

Background: Glutamatergic neurotransmission system dysregulation may play an important role in the pathophysiology of Alzheimer's disease (AD). However, reported results on glutamatergic components across brain regions are contradictory. Here, we conducted a systematic review with meta-analysis to examine whether there are consistent glutamatergic abnormalities in the human AD brain.

Basic Science and Pathogenesis.

Background: The molecular mechanisms associated with Alzheimer's Disease (AD) have been extensively studied in mouse models (Mus musculus). However, experimental research in these models is costly and time-consuming. In this context, the nematode Caenorhabditis elegans (C.

Basic Science and Pathogenesis.

Background: Animal models of amyloidosis have been instrumental in Alzheimer's disease (AD) research since they can resemble pathophysiological features of human AD. Nevertheless, each model is generated through different genetic engineering strategies, resulting in distinct phenotypes. In this context, whether AD core molecular programs are conserved among mouse models remains to be addressed.

Basic Science and Pathogenesis.

Background: Replacement, Reduction, and Refinement (3R) guidelines propose the use of alternative models to study human diseases. These models have high homology and are less onerous compared to rodents, which dominate Alzheimer's disease (AD) research. However, it is still necessary to investigate whether evolutionary components are conserved among AD models cross-species.

Basic Science and Pathogenesis.

Background: Individuals with early stages of cognitive decline face a significant stagnation in their financial capacity, leading to a decrease in quality of life. However, whether changes in brain function are associated with financial capacity remains unclear. Here, we evaluate the association between financial capacity and brain glucose metabolism.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ) plaques and tau tangles in the brain, and neurotransmission dysfunctions. Indeed, our group recently demonstrated that the γ-aminobutyric acid (GABA)ergic system is vulnerable to AD pathology in humans. However, whether this vulnerability is also present in AD rodent models is still unknown.

Clinical Manifestations.

Background: COVID-19 pandemic has brought long-lasting social, emotional, and cognitive consequences. Long COVID is characterized by a myriad of symptoms and complications that persist long after the infection, including cognitive decline and mental health impairment. This study aims to investigate depressive symptoms and cognitive performance stratified by sex and group in adults with and without long COVID.

Gut microbiota in symptomatic uncomplicated diverticular disease stratifies by severity of abdominal pain.

Objective: Patients with symptomatic uncomplicated diverticular disease (SUDD) may have a disrupted gut microbiota. However, current data are from small sample studies, and reported associations vary widely across studies. We aimed to profile the fecal microbiota in SUDD patients enrolled in primary care.

Molecular signature underlying (R)-ketamine rapid antidepressant response on anhedonic-like behavior induced by sustained exposure to stress.

Anhedonia induced by sustained stress exposure is a hallmark symptom of major depressive disorder (MDD) and in rodents, it can be accessed through the sucrose preference test (SPT). (R)-ketamine is a fast-acting antidepressant with less detrimental side effects and abuse liability compared to racemic ketamine. The present study combined high-throughput proteomics and network analysis to identify molecular mechanisms involved in chronic variable stress (CVS)-induced anhedonia and promising targets underlying (R)-ketamine rapid antidepressant response.

Nandrolone Abuse Prior to Head Trauma Mitigates Endoplasmic Reticulum Stress, Mitochondrial Bioenergetic Deficits, and Markers of Neurodegeneration.

The abuse of synthetic steroids, such as nandrolone decanoate (ND), is often associated with violent behavior, increasing the risk of traumatic brain injury (TBI). After a TBI, proteins like APP, β-amyloid peptide-42 (Aβ42), and phosphorylated tau (pTau) accumulate and trigger endoplasmic reticulum (ER) stress associated with an unfolded protein response (UPR). The involvement of mitochondrial bioenergetics in this context remains unexplored.

Omics-derived biological modules reflect metabolic brain changes in Alzheimer's disease.

Introduction: Brain glucose hypometabolism, indexed by the fluorodeoxyglucose positron emission tomography ([F]FDG-PET) imaging, is a metabolic signature of Alzheimer's disease (AD). However, the underlying biological pathways involved in these metabolic changes remain elusive.

Methods: Here, we integrated [F]FDG-PET images with blood and hippocampal transcriptomic data from cognitively unimpaired (CU, n = 445) and cognitively impaired (CI, n = 749) individuals using modular dimension reduction techniques and voxel-wise linear regression analysis.

Proteomic Insights into Biology of Bipolar Disorder: Implications for Health Complexity and Mortality.

Objective: The present study has the following objectives: 1) identify differentially expressed proteins and pathways in blood samples of BD compared to healthy controls by employing high-throughput proteomics and bioinformatics and 2) characterize disease-related molecular signatures through in-depth analysis of the differentially expressed proteins and pathways.

Methods: Blood samples from BD patients (n=10) classified into high (BD+) or poor functioning (BD-), based on functional and cognitive status, and healthy controls (n=5) were analyzed using mass spectrometry-based proteomic analysis. Bioinformatics was performed to detect biological processes, pathways, and diseases related to BD.

Drug repurposing and personalized treatment strategies for bipolar disorder using transcriptomics: an exploratory study.

Objective: The present study combined transcriptomic data and computational techniques based on gene expression signatures to identify new bioactive compounds or Food and Drug Administration-approved drugs for the treatment of bipolar disorder (BD).

Methods: Five transcriptomic datasets containing 165 blood samples from individuals with BD were selected from the Gene Expression Omnibus (GEO). The number of participants varied from six to 60, with a mean age between 35 and 48 years and a gender difference between them.

The glutamatergic system in Alzheimer's disease: a systematic review with meta-analysis.

Glutamatergic neurotransmission system dysregulation may play an important role in the pathophysiology of Alzheimer's disease (AD). However, reported results on glutamatergic components across brain regions are contradictory. Here, we conducted a systematic review with meta-analysis to examine whether there are consistent glutamatergic abnormalities in the human AD brain.

Cross-species comparative hippocampal transcriptomics in Alzheimer's disease.

Unlabelled: Alzheimer's disease (AD) is a multifactorial pathology, with most cases having a sporadic origin. Recently, knock-in (KI) mouse models, such as the novel humanized amyloid-β (hAβ)-KI, have been developed to better resemble sporadic human AD.

Methods: Here, we compared hippocampal publicly available transcriptomic profiles of transgenic (5xFAD and APP/PS1) and KI (hAβ-KI) mouse models with early- (EOAD) and late- (LOAD) onset AD patients.

Association of the fibronectin type III domain-containing protein 5 rs1746661 single nucleotide polymorphism with reduced brain glucose metabolism in elderly humans.

Fibronectin type III domain-containing protein 5 (FNDC5) and its derived hormone, irisin, have been associated with metabolic control in humans, with described FNDC5 single nucleotide polymorphisms being linked to obesity and metabolic syndrome. Decreased brain FNDC5/irisin has been reported in subjects with dementia due to Alzheimer's disease. Since impaired brain glucose metabolism develops in ageing and is prominent in Alzheimer's disease, here, we examined associations of a single nucleotide polymorphism in the FNDC5 gene (rs1746661) with brain glucose metabolism and amyloid-β deposition in a cohort of 240 cognitively unimpaired and 485 cognitively impaired elderly individuals from the Alzheimer's Disease Neuroimaging Initiative.

The GABAergic system in Alzheimer's disease: a systematic review with meta-analysis.

The γ-aminobutyric acid (GABA)ergic system is the primary inhibitory neurotransmission system in the mammalian brain. Its dysregulation has been shown in multiple brain conditions, but in Alzheimer's disease (AD) studies have provided contradictory results. Here, we conducted a systematic review with meta-analysis to investigate whether the GABAergic system is altered in AD patients compared to healthy controls (HC), following the PRISMA 2020 Statement.

Assessment of small intestinal bacterial overgrowth and methane production in patients on chronic proton-pump inhibitor treatment: prevalence and role of rifaximin in its management in primary care.

Background: Although proton pump inhibitor (PPI) drugs have considered able to induce small intestinal bacterial overgrowth (SIBO), no data are so far available from primary care (PC). We assessed the prevalence of SIBO and methane (CH4) production consequent to chronic PPI therapy using Lactulose Breath Test (LBT). Secondary aim was to explore the possible role of rifaximin in treating PPI-induced SIBO patients.

Hippocampal GFAP-positive astrocyte responses to amyloid and tau pathologies.

Introduction: In Alzheimer's disease clinical research, glial fibrillary acidic protein (GFAP) released/leaked into the cerebrospinal fluid and blood is widely measured and perceived as a biomarker of reactive astrogliosis. However, it was demonstrated that GFAP levels differ in individuals presenting with amyloid-β (Aβ) or tau pathologies. The molecular underpinnings behind this specificity are little explored.

Lower and higher volumes of physical exercise build up brain reserves against memory deficits triggered by a head injury in mice.

Decreasing neurotrophic support and impaired mitochondrial bioenergetics are key mechanisms for long-term neurodegeneration and cognitive decline after traumatic brain injury (TBI). We hypothesize that preconditioning with lower and higher volumes of physical exercise upregulates the CREB-BDNF axis and bioenergetic capability, which might serve as neural reserves against cognitive impairment after severe TBI. Using a running wheel mounted in the home cage, mice were engaged in lower (LV, 48 h free access, and 48 h locked) and higher (HV, daily free access) exercise volumes for thirty days.

A comparative study of COVID-19 transcriptional signatures between clinical samples and preclinical cell models in the search for disease master regulators and drug repositioning candidates.

Coronavirus disease 2019 (COVID-19) is an acute viral disease with millions of cases worldwide. Although the number of daily new cases and deaths has been dropping, there is still a need for therapeutic alternatives to deal with severe cases. A promising strategy to prospect new therapeutic candidates is to investigate the regulatory mechanisms involved in COVID-19 progression using integrated transcriptomics approaches.