Активность

Prior research concerning 5XFAD transgenic mice hinted that the combination of anesthesia and surgery might aggravate cognitive impairment, a consequence evidently tied to elevated levels of tau hyperphosphorylation. Prior to this study, we found GNA13, the gene that encodes G13, to be a critical hub gene driving the hyperphosphorylation of tau.

This study aims to further unravel the mechanism of action for the G13-mediated signaling pathway in its ability to modulate cofilin activation and induce autophagy impairment.

Randomly allocated to four distinct groups were 5XFAD Tg mice and their littermates (LM): LM Control, LM Anesthesia/Surgery, AD Control, and AD Anesthesia/Surgery groups. Abdominal surgeries were performed on mice from the Anesthesia/Surgery groups using 14% isoflurane anesthesia, which was sustained through continuous inhalation for up to two hours.

In contrast to the AD Control group, the AD Anesthesia/Surgery group exhibited elevated protein levels of G13, ROCK2, LPAR5, and p-tau/tau46 ratio, while displaying a reduction in p-cofilin/cofilin protein expression ratio. Nevertheless, no statistically meaningful variations in protein levels were observed between the various LM groups.

5XFAD Tg mice, but not LM mice, exhibited a potential increase in p-tau accumulation following anesthesia and surgical intervention, as this study demonstrates. It is plausible that this is directly tied to G13-mediated signaling cascades which, in turn, activate cofilin.

Anesthesia and surgery potentially contributed to an amplified p-tau accumulation in the 5XFAD Tg mouse model, as opposed to the LM mouse model, according to the findings of this study. This finding strongly suggests a correlation between G13-mediated signaling and the activation of cofilin.

The early and differential diagnosis of Alzheimer’s disease (AD) can be aided by arterial spin labeling (ASL), due to its non-radioactive properties, lack of contrast agents, greater accessibility and relatively reduced cost.

To evaluate the perfusion patterns of dementia types in a Chinese population, and assess arterial spin labeling (ASL)’s effectiveness in distinguishing Alzheimer’s Disease (AD) from cognitive unimpaired (CU), mild cognitive impairment (MCI), and frontotemporal dementia (FTD).

Participants were divided into four groups—AD, FTD, MCI, and CU—for enrollment, in accordance with clinical diagnoses from the PUMCH dementia cohort. With background suppression, a high-resolution T1-weighted scan of the whole brain provided context for the ASL image, which was acquired using a 3D spiral fast spin echo-based pseudo-continuous ASL pulse sequence. Dr. Brain Platform facilitated the regional analysis of cerebral blood flow (ml/100g/min) in all areas of interest within the cortex, using data processing methods.

Participants were categorized as follows: 66 with Alzheimer’s Disease (AD), 26 with Frontotemporal Dementia (FTD), 21 with Mild Cognitive Impairment (MCI), and 21 with Chronic Undetermined (CU) diagnoses. Bacterial signals receptor A statistical correlation was observed in AD cases between widespread hypoperfusion, affecting the neocortical temporal-parietal-occipital areas, yet sparing the hippocampus and subcortical nuclei. Significant parietal lobe hypoperfusion was strongly linked to cognitive decline in Alzheimer’s disease. The hypoperfusion observed in the parietal lobe of MCI subjects also encompassed the adjacent temporal, occipital, and posterior cingulate cortices in AD. Frontotemporal dementia (FTD) patients displayed a notable reduction in blood perfusion within the frontal and temporal cortices, encompassing subcortical structures and the anterior cingulate cortex. In Alzheimer’s Disease, hypoperfusion region symmetry was comparable bilaterally, in contrast to the more pronounced left-sided predominance observed specifically within the Frontotemporal Dementia group.

ASL hypoperfusion patterns facilitated the differentiation of Alzheimer’s Disease (AD) from Chronic Urticaria (CU), Mild Cognitive Impairment (MCI), and Frontotemporal Dementia (FTD).

The characteristics of ASL hypoperfusion, specific to each condition, were invaluable in differentiating Alzheimer’s disease from corticobasal degeneration, mild cognitive impairment, and frontotemporal dementia.

Although mild behavioral impairment (MBI) has emerged as a possible precursor to dementia, the neurobiological basis of this condition requires deeper investigation.

We endeavored to analyze the relationship between MBI and surface area, cortical thickness, and volume metrics within the temporal and parietal lobes, regions known to be strongly associated with dementia and emotional disorders.

This study, a retrospective assessment, involved 123 participants, broken down into three groups: 90 with mild cognitive impairment (MCI), 13 experiencing subjective cognitive decline (SCD), and 20 cognitively healthy (CH) individuals. Analysis of covariance (ANCOVA), incorporating sex, age, and MMSE scores as covariates, was employed to compare cortical thickness, surface area, and volume metrics in 10 brain regions between individuals with and without MBI. A distinction was drawn between groups that presented with MBI-related emotional dysregulation and those lacking the manifestation of such dysregulation through MBI.

ANCOVA demonstrated a statistically significant reduction in cortical thickness within the right parahippocampal gyrus of the MBI group (p=0.001), and also within the supramarginal gyrus (p=0.0002). Subsequent to multiple comparison adjustments, only the right supramarginal gyrus demonstrated a statistically significant reduction in size, as measured by a p-value of 0.002. In examining MBI emotional dysregulation, the right parahippocampal and supramarginal gyrus displayed significantly diminished cortical thicknesses in the MBI group, demonstrating statistical significance (p=0.003, 0.001). While multiple comparisons were undertaken and corrected, no statistically significant differences emerged (p=0.14, 0.11).

The presence of elevated MBI and emotional dysregulation correlated with diminished cortical thickness in both the right parahippocampal and supramarginal gyri. Preceding early Alzheimer’s disease (AD) is neurodegeneration within the medial temporal and parietal lobe; thus, MBI, specifically emotion dysregulation, might predict early AD even before diagnosis.

Reduced cortical thickness in the right parahippocampal and supramarginal gyri was observed among subjects with high levels of both overall MBI and emotional dysregulation. Neurodegeneration in the medial temporal and parietal lobes precedes early Alzheimer’s disease (AD), implying that brain injury markers (MBI), specifically emotional dysregulation, might foretell early AD prior to diagnostic thresholds.

To accurately diagnose Alzheimer’s disease (AD), detailed neuropsychological assessments are necessary for determining the cognitive profile. Growing knowledge about the disease’s pathophysiological processes allows for a conceptualization of AD as a biological continuum, spanning different clinical stages, and measurable using biomarkers.

In a sample of cognitively unimpaired, mild cognitive impaired, and mild dementia of the Alzheimer type participants, the NEURONORMA battery will be used to analyze the link between cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers and cognitive function. The study will also characterize cognitive profiles in mild cognitive impairment (MCI) subjects, focusing on their classification within the A/T/N system.

The NEURONORMA battery was employed to assess the 42 CU, 35 MCI, and 35 mild DAT participant groups. The proteins amyloid-beta 42 (Aβ42) peptide, total tau (t-tau), and phosphorylated tau at threonine 181 (p-tau181) were quantified in cerebrospinal fluid (CSF) to identify AD biomarkers. A determination of effect sizes, correlation coefficients, and multivariate regression was made. A/T/N variants were correlated with cognitive profiles within the MCI group, controlling for age and education level.

CSF Aβ42 levels were positively associated with cognitive outcomes, while CSF tau levels showed an inverse relationship with these outcomes. Across all pairs of cognitively impaired groups, excluding CSF measures, we detected differences in both biomarkers and cognitive outcomes. The effect size was greatest for memory tasks and biomarker ratios. Compared to individuals with normal levels of AD biomarkers (A- T- N), MCI subjects with AD pathology (A+T+N) displayed lower performance in both memory and executive functions.

The Spanish NEURONORMA cognitive battery’s utility in characterizing cognitive decline within the Alzheimer’s disease pathological sequence is further corroborated by findings from this study.

Further evidence is presented by this study regarding the validity of the Spanish NEURONORMA cognitive battery for characterizing cognitive impairment across the Alzheimer’s disease pathological progression.

The reported hippocampal atrophy in cerebral amyloid angiopathy (CAA) presents a similar profile to that of Alzheimer’s disease (AD).

To assess the role of cerebral amyloid angiopathy (CAA) pathology in partially explaining the decrease in hippocampal volume seen in patients with Alzheimer’s disease.

Inclusion criteria for the study encompassed individuals from the National Alzheimer’s Coordinating Center database, possessing a clinical diagnosis of Alzheimer’s Disease (AD) and neuropathological confirmation of AD, possibly with concurrent cerebral amyloid angiopathy (CAA). Automated FreeSurfer software processed T1-weighted MRI (T1-MRI) data, acquired on average five years before the individuals’ passing, to calculate the volumes of temporal lobe structures. Brain volume comparisons were undertaken across four cerebral amyloid angiopathy (CAA) groupings using multivariate regression analysis. The hippocampal volume, determined by T1-MRI, was found to correlate with both the Clinical Dementia Rating sum of boxes (CDRsb) score, the apolipoprotein E (APOE) genotype, and the extent of hippocampal atrophy observed during the autopsy.

A total of 231 patients, categorized by the presence of cerebrovascular amyloid angiopathy (CAA) as no, mild, moderate, or severe, were included in the study; the numbers were 45, 70, 67, and 49, respectively.