Aß Induces Neuroinflammation and Microglial M1 Polarization via cGAS-STING-IFITM3 Signaling Pathway in BV-2 Cells.

Microglia, innate immune cells of the brain, constantly monitor the dynamic changes of the brain microenvironment under physiological conditions and respond in time. Growing evidence suggests that microglia-mediated neuroinflammation plays an important role in the pathogenesis of Alzheimer's disease. In this study, we investigated that the expression of IFITM3 was significantly upregulated in microglia under the Aß treatment, and knockdown of IFITM3 in vitro suppressed the M1-like polarization of microglia. Moreover, IFITM3 was regulated by cGAS-STING signaling in activated microglia, and inhibition of cGAS-STING signaling reduces IFITM3 expression. Taken together, our findings suggested that the cGAS-STING-IFITM3 axis may be involved in Aß-induced neuroinflammation in microglia.

Trends of mitochondrial changes in AD: a bibliometric study.

Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive progress and memory loss, which eventually develops into dementia. It can cause personality disorders and decreased quality of life of patients. Currently, AD patients account for 60-70% of global dementia patients and the incidence rate of AD is increasing annually. AD not only causes pain to patients but also brings a heavy burden to the entire family. Studies have found that there is a connection between mitochondrial dysfunction and other biochemical changes in AD like classical neuropathological hallmarks (ß-amyloid and tau protein), inflammation pathways, oxidative stress, and so on. Evidence shows that early treatment targeted directly to mitochondria could extend the lifespan of model mice and decrease the relevant neuropathological markers. Therefore, research on the mitochondrial dysfunction of AD can be of potential significance for clinical treatment. To date, few bibliometric analysis articles related to mitochondrial dysfunction of AD have been published. Bibliometric analysis refers to quantitatively analyzing certain aspects of articles like publishers, authors, and countries by using statistical and mathematical methods. Combined with statistical software, a large number of papers can be converted to visualization figures and tables, which provide vital information such as keyword hotspots and the names of contributing authors. Through the bibliometric analysis method, our study aimed to provide study trends and keyword hotpots for researchers to conduct further relevant research in this field. Methods: We used the Web of Science core collection database as a literature retrieval tool to obtain data related to mitochondrial changes in Alzheimer's disease during the last 20 years. The retrieval type was [TS = (Alzheimer's disease)] ND [TS = (mitochondrion)], ranging from January 1, 2000 to June 30, 2022. VOSviewer v1.6.18, Arcgis 10.8, and HistCite pro 2.1 were used to conduct data visualization analysis. VOSviewer v1.6.18 made relevant network visualization maps of the cooperative relationship between relevant countries, institutions, and authors (co-authorship), the frequency of different keywords appearing together (co-occurrence), and the frequency of different articles cited together (co-cited). Arcgis 10.8 created the world map of publications distribution in this field and Histcite pro 2.1 was used to count the local citation score (LCS) of references. In addition, Journal Citation Reports were used to consult the latest journal import factor and JCI quartile. Results: As of June 30, 2022, from the Web of Science core collection, we selected 2,474 original articles in English, excluding the document types of the news items, meeting abstracts, and some articles that had little relevance to our theme. The United States acted as the leader and enjoyed a high reputation in this field. The University of California System was the institution that made the greatest contribution (3.64% with 90 papers). Most articles were published in the Journal of Alzheimer's Disease (8.21%, with 203 papers). The most frequently co-cited journal in Q1 was the Journal of Biological Chemistry (8,666 citations, TLS: 1039591). Russel H. Swerdlow (55 publications) was the most productive author and PH Reddy was the most co-cited author with 1,264 citations (TLS: 62971). The hotpots of mitochondrial dysfunction in AD were as follows: "oxidative stress," "amyloid-beta-protein," "tau," "apoptosis," "inflammation," "autophagy," "precursor protein," "endoplasmic-reticulum," "dynamics" and "mitochondrial unfolded protein response." Conclusion: This bibliometric analysis research will help readers rapidly identify current hotpots and milestone studies related to directions of interest in AD research.

Assessment of cognitive impairment after acute cerebral infarction with T1 relaxation time measured by MP2RAGE sequence and cerebral hemodynamic by transcranial Doppler.

Objective: This study aimed to investigate early brain microstructural changes discovered using magnetization-prepared two rapid acquisition gradient echo (MP2RAGE) sequence and cerebral hemodynamic using TCD for cognitive impairment after acute cerebral infarction. Methods: We enrolled 43 patients with acute cerebral infarction and 21 healthy people in the study, who were subjected to cognitive assessments, the MP2RAGE sequence, and a cerebral hemodynamic examination. A total of 26 brain regions of interest were investigated. Furthermore, we used cerebral hemodynamics to explain brain microstructural changes, which helped us better understand the pathophysiology of cognitive impairment after acute cerebral infarction and guide treatment. Results: T1 relaxation times in the left frontal lobe, right frontal lobe, right temporal lobe, left precuneus, left thalamus, right hippocampus, right head of caudate nucleus, and splenium of corpus callosum were substantially different across the three groups, which were significantly correlated with neuropsychological test scores. CI group patients had significantly lower cerebral blood flow velocity than those in the N-CI and Normal groups. The receiver operating curve analysis revealed that most T1 relaxation times had high sensitivity and specificity, especially on the right temporal lobe and right frontal lobe. There was a potential correlation between T1 relaxation times and MMSE scores through TCD parameters. Conclusion: The MP2RAGE sequence can detect alterations in whole brain microstructure in patients with cognitive impairment after acute cerebral infarction. Brain microstructural changes could influence cognitive function through cerebral hemodynamics. T1 relaxation times on the right temporal lobe and the right frontal lobe are expected to be a prospective biomarker of cognitive impairment after acute cerebral infarction.

Comparison of brain microstructure alterations on diffusion kurtosis imaging among Alzheimer's disease, mild cognitive impairment, and cognitively normal individuals.

Objective: Our study aimed to explore the differences in brain microstructure in patients with Alzheimer's disease (AD) and with mild cognitive impairment (MCI) and in individuals with normal cognition using diffusion kurtosis imaging (DKI) to identify a potential non-invasive biomarker of AD. Materials and methods: A total of 61 subjects were included in our study, including 20 subjects diagnosed with AD, 21 patients diagnosed with amnestic MCI, and 20 cognitively normal individuals. We acquired magnetic resonance imaging (MRI) scans, and DKI images were processed. Twelve regions of interest were drawn, and various parameters were measured and analyzed using SPSS version 11.0 software. Results: Comparative analysis showed that differences in brain regions in terms of mean diffusion (MD) and mean kurtosis (MK) between groups were the most marked. Precuneus MD, temporal MK, precuneus MK, and hippocampal MK were significantly correlated with neuropsychological test scores. Hippocampal MK showed the strongest correlation with the medial temporal lobe atrophy score (r = -0.510), and precuneus MD had the strongest correlation with the Koedam score (r = 0.463). The receiver operating curve analysis revealed that hippocampal MK exhibited better diagnostic efficacy than precuneus MD for comparisons between any group pair. Conclusion: DKI is capable of detecting differences in brain microstructure between patients with AD, patients with MCI, and cognitively normal individuals. Moreover, it compensates for the deficiencies of conventional MRI in detecting pathological changes in microstructure before the appearance of macroscopic atrophy. Hippocampus MK was the most sensitive single parameter map for differentiating patients with AD, patients with MCI, and cognitively normal individuals.

Altered Microstructural Changes Detected by Diffusion Kurtosis Imaging in Patients With Cognitive Impairment After Acute Cerebral Infarction.

Objective: To detect the microstructural changes in patients with cognitive impairment after acute cerebral infarction using diffusion kurtosis imaging (DKI). Materials and Methods: A total of 70 patients with acute cerebral infarction were divided into two groups: 35 patients with cognitive impairment (VCI group), and 35 patients without cognitive impairment (N-VCI group), according to mini-mental state examination (MMSE) score. Healthy individuals (n = 36) were selected as the normal control (NORM) group. DKI parameters from 28 different brain regions of interest (ROIs) were selected, measured, and compared. Results: VCI group patients had significantly higher mean diffusion (MD) and significantly lower mean kurtosis (MK) values in most ROIs than those in the N-VCI and NORM groups. DKI parameters in some ROIs correlated significantly with MMSE score. The splenium of corpus callosum MD was most correlated with MMSE score, the correlation coefficient was -0.652, and this parameter had good ability to distinguish patients with VCI from healthy controls; at the optimal cut-off MD value (0.9915), sensitivity was 91.4%, specificity 100%, and the area under the curve value 0.964. Conclusions: Pathological changes in some brain regions may underlie cognitive impairment after acute cerebral infarction, especially the splenium of corpus callosum. These preliminary results suggest that, in patients with VCI, DKI may be useful for assessing microstructural tissue damage.