Proteomic identification of nitrated brain proteins in amnestic mild cognitive impairment: a regional study.
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ABSTRACT:
SUBMITTER: Sultana R
PROVIDER: S-EPMC3823261 | biostudies-literature | 2007 Jul-Aug
REPOSITORIES: biostudies-literature
Publications
Proteomic identification of nitrated brain proteins in amnestic mild cognitive impairment: a regional study.
Sultana Rukhsana R Reed Tanea T Perluigi Marzia M Coccia Rafaella R Pierce William M WM Butterfield D Allan DA
Journal of cellular and molecular medicine 20070701 4
Oxidative stress is an imbalance between the level of antioxidants and oxidants in a cell. Oxidative stress has been shown in brain of subjects with mild cognitive impairment (MCI) as well Alzheimer's disease (AD). MCI is considered as a transition phase between control and AD. The focus of the current study was to identify nitrated proteins in the hippocampus and inferior parietal lobule (IPL) brain regions of subjects with amnestic MCI using proteomics. The identified nitrated proteins in MCI ...[more]
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Project description:Background and purposeManually drawn VOI-based analysis shows a decrease in magnetization transfer ratio in the hippocampus of patients with Alzheimer disease. We investigated with whole-brain voxelwise analysis the regional changes of the magnetization transfer ratio in patients with mild Alzheimer disease and patients with amnestic mild cognitive impairment.Materials and methodsTwenty patients with mild Alzheimer disease, 27 patients with amnestic mild cognitive impairment, and 30 healthy elderly control subjects were examined with high-resolution T1WI and 3-mm-thick magnetization transfer images. Whole-brain voxelwise analysis of magnetization transfer ratio maps was performed by use of Statistical Parametric Mapping 8 software and was supplemented by the analysis of the magnetization transfer ratio in FreeSurfer parcellation-derived VOIs.ResultsVoxelwise analysis showed 2 clusters of significantly decreased magnetization transfer ratio in the left hippocampus and amygdala and in the left posterior mesial temporal cortex (fusiform gyrus) of patients with Alzheimer disease as compared with control subjects but no difference between patients with amnestic mild cognitive impairment and either patients with Alzheimer disease or control subjects. VOI analysis showed that the magnetization transfer ratio in the hippocampus and amygdala was significantly lower (bilaterally) in patients with Alzheimer disease when compared with control subjects (ANOVA with Bonferroni correction, at P < .05). Mean magnetization transfer ratio values in the hippocampus and amygdala in patients with amnestic mild cognitive impairment were between those of healthy control subjects and those of patients with mild Alzheimer disease. Support vector machine-based classification demonstrated improved classification performance after inclusion of magnetization transfer ratio-related features, especially between patients with Alzheimer disease versus healthy subjects.ConclusionsBilateral but asymmetric decrease of magnetization transfer ratio reflecting microstructural changes of the residual GM is present not only in the hippocampus but also in the amygdala in patients with mild Alzheimer disease.
| S-EPMC7964837 | biostudies-literature
Project description:Amnestic MCI is often considered an early clinical stage of AD, but its subtle presentation leads to infrequent neurological evaluations. Early plasma biomarker screening during routine check-ups in community hospitals could enhance aMCI detection rates. Advances in proteomics, particularly mass spectrometry, have enabled the detection of low-abundance plasma proteins, opening new possibilities for aMCI biomarker identification. This study included 84 participants from the STAR cohort. We utilized deep plasma proteomics to detect low-abundance proteins, enriched with biofunctional magnetic beads. An early diagnostic model for aMCI was developed through bioinformatics and machine learning, with performance compared to the Simoa assay.
2024-09-26 | PXD056265 |
Project description:BackgroundResting-state functional magnetic resonance imaging studies using a regional homogeneity (ReHo) method have reported that amnestic mild cognitive impairment (aMCI) was associated with abnormalities in local functional connectivity. However, their results were not conclusive.MethodsSeed-based d Mapping was used to conduct a coordinate-based meta-analysis to identify consistent ReHo alterations in aMCI.ResultsWe identified 10 studies with 11 datasets suitable for inclusion, including 378 patients with aMCI and 435 healthy controls. This meta-analysis identified significant ReHo alterations in patients with aMCI relative to healthy controls, mainly within the default mode network (DMN) (bilateral posterior cingulate cortex [PCC], right angular gyrus, bilateral middle temporal gyri, and left parahippocampal gyrus/hippocampus), executive control network (right superior parietal lobule and dorsolateral prefrontal cortex), visual network (right lingual gyrus and left middle occipital gyrus), and sensorimotor network (right paracentral lobule/supplementary motor area, right postcentral gyrus and left posterior insula). Significant heterogeneity of ReHo alterations in the bilateral PCC, left parahippocampal gyrus/hippocampus, and right superior parietal lobule/angular gyrus was observed. Exploratory meta-regression analyses indicated that general cognitive function, gender distribution, age, and education level partially contributed to this heterogeneity.ConclusionsThis study provides provisional evidence that aMCI is associated with abnormal ReHo within the DMN, executive control network, visual network, and sensorimotor network. These local functional connectivity alterations suggest coexistence of functional deficits and compensation in these networks. These findings contribute to the modeling of brain functional connectomes and to a better understanding of the neural substrates of aMCI. Confounding factors merit much attention and warrant future investigations.
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Project description:A sensitive marker for monitoring progression of early Alzheimer's disease would help to develop and test new therapeutic strategies. The present study is aimed at investigating brain metabolism changes over time, as a potential monitoring marker, in patients with amnestic mild cognitive impairment, according to their clinical outcome (converters or non-converters), and in relation to their cognitive decline. Seventeen amnestic mild cognitive impairment patients underwent magnetic resonance imaging and 18FDG-positron emission tomography scans both at inclusion and 18 months later. Baseline and follow-up positron emission tomography data were corrected for partial volume effects and spatially normalized using magnetic resonance imaging data, scaled to the vermis and compared using SPM2. 'PET-PAC' maps reflecting metabolic per cent annual changes were created for correlation analyses with cognitive decline. In the whole sample, the greatest metabolic decrease concerned the posterior cingulate-precuneus area. Converters had significantly greater metabolic decrease than non-converters in two ventro-medial prefrontal areas, the subgenual (BA25) and anterior cingulate (BA24/32). PET-PAC in BA25 and BA24/32 combined allowed complete between-group discrimination. BA25 PET-PAC significantly correlated with both cognitive decline and PET-PAC in the hippocampal region and temporal pole, while BA24/32 PET-PAC correlated with posterior cingulate PET-PAC. Finally, the metabolic change in BA8/9/10 was inversely related to that in BA25 and showed relative increase with cognitive decline, suggesting that compensatory processes may occur in this dorso-medial prefrontal region. The observed ventro-medial prefrontal disruption is likely to reflect disconnection from the hippocampus, both indirectly through the cingulum bundle and posterior cingulate cortex for BA24/32, and directly through the uncinate fasciculus for BA25. Altogether, our findings emphasize the potential of 18FDG-positron emission tomography for monitoring early Alzheimer's disease progression.
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Project description:BACKGROUND:We tested if rates of brain atrophy accelerate in individuals with amnestic mild cognitive impairment (aMCI) as they progress to typical late onset Alzheimer disease (AD). We included comparisons to subjects with aMCI who did not progress (labeled aMCI-S) and also to cognitively normal elderly subjects (CN). METHODS:We studied 46 subjects with aMCI who progressed to AD (labeled aMCI-P), 46 CN, and 23 aMCI-S. All subjects must have had three or more serial MRI scans. Rates of brain shrinkage and ventricular expansion were measured across all available serial MRI scans in each subject. Change in volumes relative to the point at which subjects progressed to a clinical diagnosis of AD (the index date) was modeled in aMCI-P. Change in volumes relative to age was modeled in all three clinical groups. RESULTS:In aMCI-P the change in pre to post index rate (i.e., acceleration) of ventricular expansion was 1.7 cm(3)/year, and acceleration in brain shrinkage was 5.3 cm(3)/year. Brain volume declined and ventricular volume increased in all three groups with age. Volume changes decelerated with increasing age in aMCI-P, and to a lesser extent in aMCI-S, but were linear in the matched CN. Among all subjects with aMCI, rates of atrophy were greater in apolipoprotein E epsilon 4 carriers than noncarriers. CONCLUSIONS:Rates of atrophy accelerate as individuals progress from amnestic mild cognitive impairment (aMCI) to typical late onset Alzheimer disease (AD). Rates of atrophy are greater in younger than older subjects with aMCI who progressed to AD and subjects with aMCI who did not progress. We did not find that atrophy rates varied with age in 70- to 90-year-old cognitively normal subjects.
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Project description:BACKGROUND:Previous work examining normal controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI) identified substantial biological heterogeneity. We hypothesized that ADNI mild cognitive impairment (MCI) subjects would also exhibit heterogeneity with possible clinical implications. METHODS:ADNI subjects diagnosed with amnestic MCI (n=138) were clustered based on baseline magnetic resonance imaging, cerebrospinal fluid, and serum biomarkers. The clusters were compared with respect to longitudinal atrophy, cognitive trajectory, and time to conversion. RESULTS:Four clusters emerged with distinct biomarker patterns: The first cluster was biologically similar to normal controls and rarely converted to Alzheimer's disease (AD) during follow-up. The second cluster had characteristics of early Alzheimer's pathology. The third cluster showed the most severe atrophy but barely abnormal tau levels and a substantial proportion converted to clinical AD. The fourth cluster appeared to be pre-AD and nearly all converted to AD. CONCLUSIONS:Subjects with MCI who were clinically similar showed substantial heterogeneity in biomarkers.
| S-EPMC4092059 | biostudies-literature
Project description:Mild cognitive impairment (MCI) is widely regarded as an intermediate stage between typical aging and dementia, with nearly 50% of patients with amnestic MCI (aMCI) converting to Alzheimer's dementia (AD) within 30?months of follow-up (Fischer et al., 2007). The growing literature using resting-state functional magnetic resonance imaging reveals both increased and decreased connectivity in individuals with MCI and connectivity loss between the anterior and posterior components of the default mode network (DMN) throughout the course of the disease progression (Hillary et al., 2015; Sheline & Raichle, 2013; Tijms et al., 2013). In this paper, we use dynamic connectivity modeling and graph theory to identify unique brain "states," or temporal patterns of connectivity across distributed networks, to distinguish individuals with aMCI from healthy older adults (HOAs). We enrolled 44 individuals diagnosed with aMCI and 33 HOAs of comparable age and education. Our results indicated that individuals with aMCI spent significantly more time in one state in particular, whereas neural network analysis in the HOA sample revealed approximately equivalent representation across four distinct states. Among individuals with aMCI, spending a higher proportion of time in the dominant state relative to a state where participants exhibited high cost (a measure combining connectivity and distance), predicted better language performance and less perseveration. This is the first report to examine neural network dynamics in individuals with aMCI.
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Project description:Deficits in autobiographical memory appear earlier for recent than for remote life periods over the course of Alzheimer's disease (AD). The present study aims to further our understanding of this graded effect by investigating the cognitive and neural substrates of recent versus remote autobiographical memories in patients with amnestic Mild Cognitive Impairment (aMCI) thanks to an autobiographical fluency task. 20 aMCI patients and 25 Healthy elderly Controls (HC) underwent neuropsychological tests assessing remote (20-to-30 years old) and recent (the ten last years) autobiographical memory as well as episodic and semantic memory, executive function and global cognition. All patients also had a structural MRI and an FDG-PET scan. Correlations were assessed between each autobiographical memory score and the other tests as well as grey matter volume and metabolism. Within the aMCI, performances for the remote period correlated with personal semantic memory and episodic memory retrieval whereas performances for the recent period only correlated with episodic memory retrieval. Neuroimaging analyses revealed significant correlations between performances for the remote period and temporal pole and temporo-parietal cortex volumes and anterior cingulate gyrus metabolism, while performances for the recent period correlated with hippocampal volume and posterior cingulate, medial prefrontal and hippocampus metabolism. The brain regions related with the retrieval of events from the recent period showed greater atrophy/hypometabolism in aMCI patients compared to HC than those involved in remote memories. Recall of recent memories essentially relies on episodic memory processes and brain network while remote memories also involve other processes such as semantic memory. This is consistent with the semanticization of memories with time and may explain the better resistance of remote memory in AD.
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Project description:Background and Purpose: It is well known that there is a wide range of different pathological stages related to Alzheimer's disease (AD) among patients with amnestic mild cognitive impairment (aMCI). Further refinement of the stages based on neuropsychological and neuroimaging methods is important for earlier disease detection, as well as for the development and evaluation of disease-modifying interventions. Materials and Methods: In this cross-sectional study, 125 aMCI patients were classified into declined progressively three stages of mild, moderate and severe, utilizing the extreme groups approach (EGA) based on their memory function. Fifty-two patients, in addition to 24 cognitively normal subjects, were included in further structural MRI analyses. Characteristics of cognitive functions and brain structures across these newly defined stages were explored through general linear models. Results: Almost all the non-memory cognitive functions showed progressive decline as memory function deteriorated. In addition, medial structures including the right hippocampus, right lingual and left fusiform gyrus, presented with greater gray matter (GM) atrophy during the later stages of aMCI (corrected p < 0.05). Correlations were found between GM volume of the lingual gyrus and processing speed (r = 0.419, p = 0.003) and between the fusiform gyrus and general cognitive function (r = 0.281, p = 0.046). Moreover, both cognitive function and GM volume presented non-linear trajectories over stages of aMCI. Conclusion: Our study characterized the cognitive profiles along with the degree of episodic memory impairment, and these three stages of aMCI showed non-linear progressive decline in cognitive functions and GM volumes.
| S-EPMC5222841 | biostudies-literature
Project description:Background: Amnestic mild cognitive impairment (aMCI) has a high conversion risk to Alzheimer's disease (AD). The aMCI patients may have only a memory deficit (single-domain-aMCI, sd-aMCI) or deficits in multiple cognitive domains (multiple-domain-aMCI, md-aMCI). However, differences in intrinsic brain activity between these two sub-types remain unclear. Method: Neuropsychological and resting-state functional magnetic resonance imaging (fMRI) data were acquired from 24 patients with sd-aMCI, 23 patients with md-aMCI, and 32 healthy controls (HCs). We used the fractional amplitude of low-frequency fluctuation (fALFF) to characterize the intensity of spontaneous brain activity. The analysis of covariance (ANCOVA) and post hoc tests was performed to determine the between-group differences in fALFF. Results: We found higher fALFF in left-sided superior-to-middle frontal gyri and middle-to-inferior temporal gyri in sd-aMCI compared to both the md-aMCI and HCs. Conversely, a lower fALFF was found in the left inferior parietal lobe in both the md-aMCI and sd-aMCI patients. The fALFF values in the left middle and inferior temporal gyri were correlated with cognitive performances. Conclusion: The gradual reduction in the left inferior parietal lobe from single to multiple domain aMCI suggest a functional inefficiency underlying cognitive impairment, while increased activity in the frontal and temporal gyri in sd-aMCI rather than md-aMCI might indicate functional compensation. This study indicates differential functional profiles in the sd-aMCI and md-aMCI, which may be helpful for the prediction of the future conversion of aMCI to AD.
| S-EPMC7002564 | biostudies-literature