scholarly journals Decreased Global EEG Synchronization in Amyloid Positive Mild Cognitive Impairment and Alzheimer’s Disease Patients—Relationship to APOE ε4

2021 ◽  
Vol 11 (10) ◽  
pp. 1359
Author(s):  
Una Smailovic ◽  
Charlotte Johansson ◽  
Thomas Koenig ◽  
Ingemar Kåreholt ◽  
Caroline Graff ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Quantitative Eeg ◽  
Global Field ◽  
Compensatory Mechanism ◽  
Global Field Power ◽  
Apoe Ε4 ◽  
Ε4 Allele

The apolipoprotein E (APOE) ε4 allele is a risk factor for Alzheimer’s disease (AD) that has been linked to changes in brain structure and function as well as to different biological subtypes of the disease. The present study aimed to investigate the association of APOE ε4 genotypes with brain functional impairment, as assessed by quantitative EEG (qEEG) in patients on the AD continuum. The study population included 101 amyloid positive patients diagnosed with mild cognitive impairment (MCI) (n = 50) and AD (n = 51) that underwent resting-state EEG recording and CSF Aβ42 analysis. In total, 31 patients were APOE ε4 non-carriers, 42 were carriers of one, and 28 were carriers of two APOE ε4 alleles. Quantitative EEG analysis included computation of the global field power (GFP) and global field synchronization (GFS) in conventional frequency bands. Amyloid positive patients who were carriers of APOE ε4 allele(s) had significantly higher GFP beta and significantly lower GFS in theta and beta bands compared to APOE ε4 non-carriers. Increased global EEG power in beta band in APOE ε4 carriers may represent a brain functional compensatory mechanism that offsets global EEG slowing in AD patients. Our findings suggest that decreased EEG measures of global synchronization in theta and beta bands reflect brain functional deficits related to the APOE ε4 genotype in patients that are on a biomarker-verified AD continuum.

Apolipoprotein E allele 4 is not a sufficient or a necessary predictor of the development of Mild Cognitive Impairment

2010 ◽  
Vol 25 (1) ◽  
pp. 15-18 ◽  
Author(s):  
R. Heun ◽  
U. Gühne ◽  
T. Luck ◽  
M.C. Angermeyer ◽  
U. Ueberham ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Apolipoprotein E ◽  
Target Population ◽  
Population Based ◽  
Initial Development ◽  
Apoe Ε4 ◽  
Ε4 Allele

AbstractThe presence of Mild Cognitive Impairment (MCI) and of an apolipoprotein E (apoE) ε4 allele both predict the development of Alzheimer's disease. However, the extent to which this allele also predicts the development of MCI is unclear even though MCI is an early transitional stage in the development of Alzheimer's disease. The present study investigates the prevalence of the apoE ε4 allele in incipient MCI. Participants were recruited from the population-based Leipzig Longitudinal Study of the Aged (LEILA75+). All subjects who were initially cognitively healthy, i.e. did not meet MCI criteria described by Petersen [Petersen RC. Mild cognitive impairment. J Intern Med 2004; 256(3): 183–94], and whose apoE status could be determined were followed-up. After 4.5 years, 15.5% of the cognitively healthy target population had developed MCI. The frequencies of the apoE ε4 genotype did not differ between individuals with incipient MCI (12.9%) and individuals who remained cognitively healthy during the study (18.4%, p > 0.5). Consequently, the apoE ε4 genotype is not a necessary or sufficient risk factor for MCI. Further studies need to investigate the influence of the whole range of genetic and environmental risk factors on the course of Alzheimer's disease including the initial development of MCI and the later conversion to Alzheimer's disease.

The Role of Apolipoprotein E ε4 in Early and Late Mild Cognitive Impairment

2021 ◽  
Vol 84 (6) ◽  
pp. 472-480
Author(s):  
Yulin Luo ◽  
Li Tan ◽  
Joseph Therriault ◽  
Hua Zhang ◽  
Ying Gao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Apolipoprotein E ◽  
Amyloid Β ◽  
Disease Assessment ◽  
Tau Pathology ◽  
Ε4 Allele ◽  
State Examination

<b><i>Background:</i></b> Apolipoprotein E (<i>APOE</i>) ε4 is highly associated with mild cognitive impairment (MCI). However, the specific influence of <i>APOE</i> ε4 status on tau pathology and cognitive decline in early MCI (EMCI) and late MCI (LMCI) is poorly understood. Our goal was to evaluate the association of <i>APOE</i> ε4 with cerebrospinal fluid (CSF) tau levels and cognition in EMCI and LMCI patients in the Alzheimer’s Disease Neuroimaging Initiative database, and whether this association was mediated by amyloid-β (Aβ). <b><i>Methods:</i></b> Participants were 269 cognitively normal (CN), 262 EMCI, and 344 LMCI patients. They underwent CSF Aβ42 and tau detection, <i>APOE</i> ε4 genotyping, Mini-Mental State Examination, (MMSE), and Alzheimer’s disease assessment scale (ADAS)-cog assessments. Linear regressions were used to examine the relation of <i>APOE</i> ε4 and CSF tau levels and cognitive scores in persons with and without Aβ deposition (Aβ+ and Aβ−). <b><i>Results:</i></b> The prevalence of <i>APOE</i> ε4 is higher in EMCI and LMCI than in CN (<i>p</i> &#x3c; 0.001 for both), and in LMCI than in EMCI (<i>p</i> = 0.001). <i>APOE</i> ε4 allele was significantly higher in Aβ+ subjects than in Aβ− subjects (<i>p</i> &#x3c; 0.001). Subjects who had a lower CSF Aβ42 level and were <i>APOE</i> ε4-positive experienced higher levels of CSF tau and cognitive scores in EMCI and/or LMCI. <b><i>Conclusions:</i></b> An <i>APOE</i> ε4 allele is associated with increased CSF tau and worse cognition in both EMCI and LMCI, and this association may be mediated by Aβ. We conclude that <i>APOE</i> ε4 may be an important mediator of tau pathology and cognition in the early stages of AD.

scholarly journals β-Amyloid is Associated with Aberrant Metabolic Connectivity in Subjects with Mild Cognitive Impairment

2014 ◽  
Vol 34 (7) ◽  
pp. 1169-1179 ◽  
Author(s):  
Felix Carbonell ◽  
Arnaud Charil ◽  
Alex P Zijdenbos ◽  
Alan C Evans ◽  
Barry J Bedell ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Disease Process ◽  
Brain Regions ◽  
Apoe Ε4 ◽  
Positron Emission ◽  
Β Amyloid ◽  
Glucose Hypometabolism

Positron emission tomography (PET) studies using [18F]2-fluoro-2-deoxyglucose (FDG) have identified a well-defined pattern of glucose hypometabolism in Alzheimer's disease (AD). The assessment of the metabolic relationship among brain regions has the potential to provide unique information regarding the disease process. Previous studies of metabolic correlation patterns have demonstrated alterations in AD subjects relative to age-matched, healthy control subjects. The objective of this study was to examine the associations between β-amyloid, apolipoprotein ε4 (APOE ε4) genotype, and metabolic correlations patterns in subjects diagnosed with mild cognitive impairment (MCI). Mild cognitive impairment subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were categorized into β-amyloid-low and β-amyloid-high groups, based on quantitative analysis of [18F]florbetapir PET scans, and APOE ε4 non-carriers and carriers based on genotyping. We generated voxel-wise metabolic correlation strength maps across the entire cerebral cortex for each group, and, subsequently, performed a seed-based analysis. We found that the APOE ε4 genotype was closely related to regional glucose hypometabolism, while elevated, fibrillar β-amyloid burden was associated with specific derangements of the metabolic correlation patterns.

scholarly journals The role of Interleukin-33 in patients with mild cognitive impairment and Alzheimer’s disease

2020 ◽  
Author(s):  
Chih-Sung Liang ◽  
Kuan-Pin Su ◽  
Chia-Lin Tsai ◽  
Jiunn-Tay Lee ◽  
Che-Sheng Chu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Clinical Studies ◽  
Digit Span ◽  
Verbal Learning ◽  
Positive Trend ◽  
Apoe Ε4

Abstract Background: The neuroprotective role of interleukin (IL)-33 is supported by numerous pre-clinical studies, but it remains uninvestigated in clinical studies of Alzheimer’s disease (AD). We aimed to examine the association between human blood levels of IL-33 and cognitive preservation in amnestic mild cognitive impairment (aMCI) and AD.Methods: A total of 100 participants (26 controls, 35 aMCI patients, and 39 AD patients) completed two Mini Mental State Examination (MMSE) over a 1-year interval. In all 100 participants at the second MMSE, we examined the plasma levels of IL-33, IL-β, IL-1 receptor agonist (IL-1RA), beta amyloid (Aβ), and tau and apolipoprotein E (ApoE) genotyping; we also performed Hopkins Verbal Learning Test, Trail Making Test, forward and backward digit span, and Clinical Dementia Rating. Results: IL-33 expression showed a positive trend among controls (1/26 = 3.8%), aMCI (9/35 = 25.7%), and AD (17/39 = 43.6%) (trend analysis: P < 0.001). Patients expressing IL-33 preserved their cognitive function compared with IL-33 non-expressing patients (1-year ΔMMSE: 0.16 ± 1.6 vs -1.5 ± 2.6; P = 0.006). The cognitive preservation was not associated with the lower levels of Aβ, tau, and ApoE ε4, while higher levels of ApoE ε4 and phosphorylated tau were indeed associated with cognitive decline. The aMCI patients with AD conversion during study period had higher proportion of IL-33(-) than non-AD converters (90.9% vs 53.3%, P = 0.04).Conclusions: IL-33 or its associated signaling pathways may represent a new treatment paradigm for aMCI and AD.

scholarly journals Genetic risk factor APOEε4 associates with plasma amyloid beta in amnestic mild cognitive impairment and alzheimer’s disease

2016 ◽  
Vol 25 (1) ◽  
pp. 44-50
Author(s):  
Rocksy F.V. Situmeang ◽  
Eka J. Wahjoepramono ◽  
Cahyono Kaelan ◽  
Jan S. Purba ◽  
Budhianto Suhadi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Genetic Risk ◽  
Normal Aging ◽  
Amnestic Mild Cognitive Impairment ◽  
Genetic Risk Factor ◽  
Ε4 Allele

Background: APOEε4 is a strong genetic risk factor for Alzheimer’s disease (AD). AD itself has been associated with reduced Aβ clearance from the brain and plasma. Understanding the potential pathogenic link between APOEε4 and plasma Aβ might allow for earlier identification of people at risk of developing AD. The aim of this study is to find out the correlation between APOEε4 and plasma Aβ in amnestic mild cognitive impairment (aMCI) and AD patients.Methods: This is a comparative cross-sectional study of patients attending a memory clinic in Siloam Hospital Lippo Karawaci, Tangerang, during the period of 2013-2014. Subjects were categorized into three categories: normal aging, aMCI, and AD. We performed blood test to examine APOEε4, plasma Aβ4o level, and plasma Aβ42 level. All data analyses were performed using correlation test and logistic regression.Results: Sixty subjects (normal aging = 23, aMCI = 17, AD = 20) were included. There were 19 (31.7%) subjects with APOEε4 positive. Subjects carrying ε4 allele were more likely to have AD by 3.9-fold than subjects with APOE ε4 allele negative. There is a significant difference between the mean of plasma Aβ40 in aMCI group and AD group. We also found correlation between APOEε4 (+) and higher plasma Aβ42 (p<0.05).Conclusion: There is a correlation between APOEε4 and plasma Aβ42 level, which supports the hypothesis that this genetic isoform accelerates the rate and progression of AD through Aβ-dependent pathways.

Can Neuroimaging Techniques Identify Individuals at Risk of Developing Alzheimer's Disease?

1997 ◽  
Vol 9 (4) ◽  
pp. 389-403 ◽  
Author(s):  
Cássio M. C. Bottino ◽  
Osvaldo P. Almeida
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
At Risk ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Single Photon ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Ε4 Allele ◽  
Neuroimaging Techniques

Recent studies indicate that neuroimaging techniques such as magnetic resonance imaging, positron emission tomography, and single-photon emission computed tomography can accurately differentiate patients with Alzheimer's disease (AD) from elderly controls. This report reviews the results of neuroimaging studies of two at-risk populations: subjects with the ε4 allele of the apolipoprotein E and those with mild cognitive impairment. The results of the work published to date indicate that the presence of the ε4 allele is a risk factor for AD and that its predictive validity can be enhanced by neuropsychological and/or neuroimaging evaluation. The results also show that patients with mild cognitive impairment display a number of structural and functional imaging abnormalities that are more pronounced in the temporal and parietal lobes. We suggest that the use of neuroimaging techniques can improve the detection of subjects early in the course of AD, although the sensitivity and the specificity of this approach still await a more detailed prospective evaluation.

scholarly journals Increased CSF-BACE 1 activity is associated with ApoE-ε4 genotype in subjects with mild cognitive impairment and Alzheimer's disease

Brain ◽  
2008 ◽  
Vol 131 (5) ◽  
pp. 1252-1258 ◽  
Author(s):  
Michael Ewers ◽  
Zhenyu Zhong ◽  
Katharina Bürger ◽  
Anders Wallin ◽  
Kaj Blennow ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Apoe Ε4 ◽  
Bace 1

Prevalence of Apolipoprotein E Polymorphisms in Alzheimer’s Disease, Mild Cognitive Impairment, and Healthy Elderly: A Northern Greece Study

2018 ◽  
Vol 18 (4) ◽  
pp. 216-224 ◽  
Author(s):  
Anthoula C. Tsolaki ◽  
Olympia Gatzima ◽  
Makrina Daniilidou ◽  
Eutuxia Lazarou ◽  
Panagiotis D. Bamidis ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Apolipoprotein E ◽  
Apoe Genotype ◽  
Dependent Manner ◽  
Apoe Ε4 ◽  
Healthy Elderly ◽  
Increased Risk

Background: Apolipoprotein E ε4 allele (APOEε4) is a major genetic risk factor for Alzheimer’s disease (AD). APOEε4 carriers have a higher risk of cognitive impairment and AD in a gene dose-dependent manner. The above notion is investigated in the Greek population. Methods: A sample of 1,703 subjects (967 AD patients, 576 mild cognitive impairment [MCI] and 160 Healthy Elderly), was genotyped for APOE from 2008 to 2017. DNA was extracted from peripheral blood using the QIAamp Blood DNA purification kit (Qiagen Inc., USA). Descriptive statistics, one-way analysis of variance with Bonferroni post hoc tests, Pearson chi-square test, and binary logistic regression models were used for the statistical analysis. Results: The APOE genotype and allele frequencies in AD group were significantly different from those in the Control and MCI groups. The frequencies of ε4/4 homozygotes were 1.9, 1.6, and 5.7%, while the ε4/– carriers’ distribution was 22.5, 24.1, and 37.4% in the Control, MCI, and AD groups respectively. The estimated odds of ε4/4 for AD was 5.731-fold higher compared to the estimated odds of ε3/3. The interaction between gender and APOE did not have a significant effect on the odds for MCI (p = 0.942) and AD (p = 0.984). Conclusion: In Greece, APOE ε4 presence is related to an increased risk for AD in a dose-related manner. Contrary to long-standing views, men and women with the APOE ε4 genotype have nearly the same odds of developing MCI and AD.

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