Alzheimer's disease-associated CD83(+) microglia are linked with increased immunoglobulin G4 and human cytomegalovirus in the gut, vagal nerve, and brain.

Introduction: While there may be microbial contributions to Alzheimer's disease (AD), findings have been inconclusive. We recently reported an AD-associated CD83(+) microglia subtype associated with increased immunoglobulin G4 (IgG4) in the transverse colon (TC).

Methods: We used immunohistochemistry (IHC), IgG4 repertoire profiling, and brain organoid experiments to explore this association.

Exposure duration and cerebral amyloidosis in the olfactory cortex of World Trade Center responders: A positron emission tomography and magnetic resonance imaging study.

Background: Amyloid-β proteins, a hallmark of Alzheimer's disease, are believed to play an adaptive role in the cerebral immune response.

Objective: Amyloid is believed to play a role in cerebral immune response and could play a similar role in response to air pollution exposures. In the present study, we examined whether WTC exposure duration was associated with cerebral amyloidosis in WTC responders.

Intranasal long R3 insulin-like growth factor-1 treatment promotes amyloid plaque remodeling in cerebral cortex but fails to preserve cognitive function in male 5XFAD mice.

Background: Insulin-like growth factor-1 (IGF-1) promotes neurogenesis, cell survival, and glial function, making it a promising candidate therapy in Alzheimer's disease (AD).

Objective: Long arginine 3-IGF-1 (LR3-IGF-1) is a potent IGF-1 analogue. We sought to determine whether intranasal (IN) LR3 treatment would delay cognitive decline and pathology in 5XFAD mice.

Beneficial effects of physical exercise and an orally active mGluR2/3 antagonist pro-drug on neurogenesis and behavior in an Alzheimer's amyloidosis model.

Background: Modulation of physical activity represents an important intervention that may delay, slow, or prevent mild cognitive impairment (MCI) or dementia due to Alzheimer's disease (AD). One mechanism proposed to underlie the beneficial effect of physical exercise (PE) involves the apparent stimulation of adult hippocampal neurogenesis (AHN). BCI-838 is a pro-drug whose active metabolite BCI-632 is a negative allosteric modulator at group II metabotropic glutamate receptors (mGluR2/3).

Sequences Related to Chimay Rhabdovirus Are Widely Distributed in Ticks across England and Wales.

Ticks are the main arthropod vector of pathogens to humans and livestock in the British Isles. Despite their role as a vector of disease, many aspects of tick biology, ecology, and microbial association are poorly understood. To address this, we investigated the composition of the microbiome of adult and nymphal ticks.

miR155, TREM2, INPP5D: Disease stage and cell type are essential considerations when targeting clinical interventions based on mouse models of Alzheimer's amyloidopathy.

Studies of microglial gene manipulation in mouse models of Alzheimer's disease (AD) amyloidopathy can cause unpredictable effects on various key endpoints, including amyloidosis, inflammation, neuritic dystrophy, neurodegeneration, and learning behavior. In this Correspondence, we discuss three examples, microRNA 155 (miR155), TREM2, and INPP5D, in which observed results have been difficult to reconcile with predicted results based on precedent, because these six key endpoints do not reliably track together. The pathogenesis of AD involves multiple cell types and complex events that may change with disease stage.

Dual-specificity protein phosphatase 6 (DUSP6) overexpression reduces amyloid load and improves memory deficits in male 5xFAD mice.

Background: Dual specificity protein phosphatase 6 (DUSP6) was recently identified as a key hub gene in a causal network that regulates late-onset Alzheimer's disease. Importantly, decreased DUSP6 levels are correlated with an increased clinical dementia rating in human subjects, and DUSP6 levels are additionally decreased in the 5xFAD amyloidopathy mouse model.

Methods: AAV5-DUSP6 or AAV5-GFP (control) were stereotactically injected into the dorsal hippocampus (dHc) of female and male 5xFAD or wild type mice to overexpress DUSP6 or GFP.

Ecotype Analysis in Cattle from Great Britain.

() is the aetiological agent of tick-borne fever in cattle and sheep, and granulocytic anaplasmosis in human and dogs. Livestock, companion animal and human infections with have been reported globally. Across England and Wales, two isolates (called ecotypes) have been reported in ticks.

Multicenter Randomized Trial Assessing MRI and Image-guided Biopsy for Suspected Prostate Cancer: The MULTIPROS Study.

Background The optimal diagnostic pathway for prostate cancer (PCa) is evolving, requiring further evaluation in a randomized controlled trial. Purpose To assess the diagnostic accuracy of prebiopsy multiparametric MRI in the identification of clinically significant PCa (csPCa) using radical prostatectomy (RP) specimens as the reference standard, and to test the diagnostic accuracy of combined US and MRI fusion-targeted biopsy with systematic biopsies. Materials and Methods In a prospective randomized controlled trial including university hospitals, men with suspected PCa were recruited between January 2015 and August 2020 to assess the diagnostic accuracy of multiparametric MRI before biopsy in detection of csPCa at biopsy and RP histopathologic structure (primary outcome).

Systemically administered alcadein peptide p3-Alcβ neutralizes brain Alzheimer's Aβ oligomers.

Alcadeins are among the 90 known substrates for γ-secretase, the aspartyl proteinase complex that liberates the amyloid β (Aβ) peptide by intramembranous cleavage of the ß-carboxy terminal fragment of the Alzheimer's amyloid precursor protein (APP). A new study by Hata et al. provides some surprising results regarding a potential role for alcadeins and their fragments in the prevention and/or treatment of the dementia of Alzheimer's disease (AD).

Plasma amyloid beta 40/42, phosphorylated tau 181, and neurofilament light are associated with cognitive impairment and neuropathological changes among World Trade Center responders: A prospective cohort study of exposures and cognitive aging at midlife.

Introduction: World Trade Center (WTC) responders are experiencing a high risk of mild cognitive impairment (MCI) and dementia, though the etiology remains inadequately characterized. This study investigated whether WTC exposures and chronic post-traumatic stress disorder (PTSD) were correlated with plasma biomarkers characteristic of Alzheimer's disease (AD) neuropathology.

Methods: Eligible participants included WTC-exposed individuals with a baseline cognitive assessment and available plasma sample.

ApoE Alzheimer's Disease Aβ-amyloid plaque morphology varies according to APOE isotype.

Background: The apolipoprotein E (, gene; apoE, protein) ε4 allele is the most common identified genetic risk factor for typical late-onset sporadic Alzheimer's disease (AD). Each ε4 allele roughly triples the relative risk for AD compared to that of the reference allele, ε3.

Methods: We have employed hyperspectral fluorescence imaging with an amyloidspecific, conformation-sensing probe, p-FTAA, to elucidate protein aggregate structure and morphology in fresh frozen prefrontal cortex samples from human postmortem AD brain tissue samples from patients homozygous for either ε3 or ε4.

BCI-838, an orally active mGluR2/3 receptor antagonist pro-drug, rescues learning behavior deficits in the PS19 MAPT mouse model of tauopathy.

Tauopathies are a heterogeneous group of neurodegenerative disorders that are clinically and pathologically distinct from Alzheimer's disease (AD) having tau inclusions in neurons and/or glia as their most prominent neuropathological feature. BCI-838 (MGS00210) is a group II metabotropic glutamate receptor (mGluR2/3) antagonist pro-drug. Previously, we reported that orally administered BCI-838 improved learning behavior and reduced anxiety in Dutch (APP) transgenic mice, a model of the pathological accumulation of Aβ oligomers found in AD.

The contribution of amyloid deposition in the aortic valve to calcification and aortic stenosis.

Calcific aortic valve disease (CAVD) and stenosis have a complex pathogenesis, and no therapies are available that can halt or slow their progression. Several studies have shown the presence of apolipoprotein-related amyloid deposits in close proximity to calcified areas in diseased aortic valves. In this Perspective, we explore a possible relationship between amyloid deposits, calcification and the development of aortic valve stenosis.

Among psychedelic-experienced users, only past use of psilocybin reliably predicts nature relatedness.

Background: Past research reports a positive relationship between experience with classic serotonergic psychedelics and nature relatedness (NR). However, these studies typically do not distinguish between different psychedelic compounds, which have a unique psychopharmacology and may be used in specific contexts and with different intentions. Likewise, it is not clear whether these findings can be attributed to substance use per se or unrelated variables that differentiate psychedelic users from nonusers.