Presence Of Apolipoprotein E Ε4 Allele Research Articles

Alzheimer's disease pathology: pathways between chronic vascular risk factors and blood-brain barrier dysfunction in a cohort of patients with different types of dementia.

Blood brain barrier (BBB) breakdown is considered a potential mechanism of dementia. The Alzheimer's disease (AD) biomarkers and vascular factors are also associated with BBB permeability. In the present study, the combination effects of neuropathological biomarkers of AD and chronic vascular risk factors for BBB were investigated. The cerebrospinal fluid (CSF)/serum albumin ratio (Qalb), an indicator of BBB permeability, was measured in a total of 95 hospitalized dementia patients. The demographics, clinical information, and laboratory tests were collected from the inpatient records. The CSF neuropathological biomarkers of AD and apolipoprotein E (APOE) genotype were also collected. The mediation analysis model was used to calculate the associations among neuropathological biomarkers of AD (mediator), the Qalb, and chronic vascular risk factors. Three types of dementia, AD (n = 52), Lewy body dementia (LBD, n = 19), and frontotemporal lobar degeneration (n = 24), were included with a mean Qalb of 7.18 (± 4.36). The Qalb was significantly higher in dementia patients with type 2 diabetes mellitus (T2DM, p = 0.004) but did not differ based on the presence of APOE ε4 allele, CMBs, or amyloid/tau/neurodegeneration (ATN) framework. The Qalb was negatively associated with the levels of Aβ1-42 (B = -20.775, p = 0.009) and Aβ1-40 (B = -305.417, p = 0.005) and positively associated with the presence of T2DM (B = 3.382, p < 0.001) and the levels of glycosylated hemoglobin (GHb, B = 1.163, p < 0.001) and fasting blood glucose (FBG, B = 1.443, p < 0.001). GHb is a direct chronic vascular risk factor for higher Qalb (total effect B = 1.135, 95% CI: 0.611-1.659, p < 0.001). Ratios of Aβ1-42/Aβ1-40 or t-tau/Aβ1-42 were mediators of the association between the Qalb and GHb; the direct effect of GHb on the Qalb was 1.178 (95% CI: 0.662-1.694, p < 0.001). Glucose exposure can directly or indirectly affect BBB integrity through Aβ and tau, indicating glucose affects BBB breakdown and glucose stability plays an important role in dementia protection and management.

The presence and co-incidence of geriatric syndromes in older patients with mild-moderate Lewy body dementia

IntroductionGeriatric symptoms are common in dementia cases, while few studies have focused on these symptoms in Lewy body dementia (LBD). The purpose of this study is to investigate the distributions of Apolipoprotein E (APOE) ε4 and geriatric symptoms, and explore their associaitons in Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD).MethodsA retrospective study with 185 mild-moderate probable DLB (n = 93) and PDD (n = 92) patients was assigned. Demographic and clinical characteristics, neuropsychological assessments, and APOE genotypes were recorded. Description, correlation and logistic regression models were used to analyze the presence of geriatric symptom complaints and their associations with APOE ε4.ResultsDLB patients displayed more frequency of fluctuating cognition, visual hallucination, rapid eye movement sleep behavior disorder, delusion, depression, anxiety, apathy, and loss of appetite, whereas the PDD cases had constipation, fear of falling, and insomnia more frequently. The APOE ε4 allele was more common in DLB than PDD (29.9% vs. 7.0%, p < 0.001), and the patients with DLB + APOE ε4 (+) were presented more delusions (p = 0.005) and apathy (p = 0.007) than patients with PDD + APOE ε4 (+). We also found that the APOE ε4 allele was significantly associated with hyperhidrosis (OR = 3.472, 95%CI: 1.082–11.144, p = 0.036) and depression (OR = 3.002, 95%CI: 1.079–8.353, p = 0.035) in DLB patients, while there were no significant associations between APOE ε4 allele and the age at visit, the age at onset, scores of MDS-UPDRS III, H&Y stage, ADL, MMSE, MOCA and NPI, as well as the presences of fluctuating cognition, VH, parkinsonism and RBD in both groups.ConclusionThe presence and co-incidence of geriatric symptoms are common in patients with mild-moderate LBD. The presence of APOE ε4 allele is associated with hyperhidrosis and depression, but not global cognition, activitives of daily life, motor function and other neuropsychitric symptoms in DLB. These findings improve the awareness of geriatric symptoms, and contribute to the healthcare management of mild-moderate DLB and PDD.

Incidence and Cognitive Decline of Alzheimer's Disease and Other Dementia by Apolipoprotein ε4 Allele Presence: A Community-Based Cohort Study in Korean Elderly.

Objective This study aimed to investigate the role of apolipoprotein E (APOE) ε4 allele to the incidence of dementia and cognitive decline in a cohort of a Korean community. Methods From a community-based dementia-free cohort, 357 participants were genotyped. Participants underwent 2 cognitive assessments separated by a hiatus between 6 to 7 years and were diagnosed as healthy control (n=297), Alzheimer’s disease (AD) (n=44), and other dementia (n=16) at the second assessment. Incidence risk and onset age of disease according to APOE ε4 presence were analyzed in AD and other dementia. Differences in cognitive decline rate depending on APOE ε4 were also examined across all groups. Results The relative risks and onset age of dementia were not different by the presence of the APOE ε4 allele. Cognitive decline was more prominent in the presence of APOE ε4 allele (score change=7.4) than non-presence (score change=3.1), and this interaction was significant only in the AD group (F=10.51, p=0.003). Conclusion The APOE ε4 alleles can be a critical factor in predicting cognitive change for AD in the Korean community population but not in predicting AD incidence. This finding suggest that clinicians consider the presence of APOE ε4 allele examining patients with rapid declining dementia.

Decreased Function of Delayed Recall in Non-demented Elderly Subjects With Apolipoprotein E ε4 Allele.

Apolipoprotein E (APOE) is the major genetic risk factor for late-onset Alzheimer’s disease (AD). Inconsistent results about the role of APOE ε4 alleles on cognitive decline of community non-dementia elderly have been reported. This study aimed to examine the relationship between APOE ε4 allele and cognitive abilities in the subjects aged 60 years or above from a community in Shanghai, China. A total of 1445 participants voluntarily accepted the analysis of APOE genotype and global cognitive assay using the Mini Mental Status Evaluation (MMSE). There were no significant differences in total MMSE scores between APOE ε4 carriers and non-carriers. In addition, the performances of orientation, registration, attention, calculation, and language had no significant differences between subjects with and without APOE ε4 allele. However, stratified analysis showed that the performance of delayed recall in subjects with APOE ε4 allele was inferior to that in non-ε4 carriers (p = 0.041). Further, the multiple linear regression analysis showed the significant correlations between the presence of APOE ε4 allele and the scores of the delayed memory subdomain if age, gender, and education were adjusted but no significant correlations if the related factors were not adjusted. The results indicate that significant impact of APOE ε4 allele only on the delay memory but not on global or other sub-domains of cognitive abilities.

Effect of Low-Dose Statins and Apolipoprotein E Genotype on Cerebral Small Vessel Disease in Older Hypertensive Patients: A Subgroup Analysis of a Randomized Clinical Trial

ObjectivesTo investigate the effect of low-dose statins and apolipoprotein E (APOE) genotypes on cerebral small vessel disease (CSVD) to prevent CSVD in older hypertensive patients. DesignA subgroup analysis of a randomized clinical trial. SettingShandong area, China. ParticipantsHypertensive patients aged ≥60 years were recruited from April 2008 to November 2010. MeasurementsPatients were randomly assigned to rosuvastatin (10 mg/day) or placebo groups. APOE genotypes were categorized as ε4 carriers and non-ε4 carriers. White matter hyperintensities (WMH), Fazekas scale, lacunes, and microbleeds were assessed. ResultsAfter an average of intervention period of 61.8 months, WMH volume increased 1.45 ± 0.52 mL. There were 107 new-incident Fazekas scale ≥2, 65 new-incident lacunes, and 63 new-incident microbleeds. The increase in WMH volume was significantly lower in the rosuvastatin group than in the placebo group and was higher in APOE ε4 carriers than in non-ε4 carriers (all adjusted P < .001). The risk of new-incident Fazekas scale ≥2 was higher in the placebo group than in the rosuvastatin group (hazard ratio 2.150, 95% confidence interval 1.443–3.203; P < .001). APOE ε4 carriers were associated with an increased risk of new-incident Fazekas scale ≥2 compared with non-ε4 carriers (hazard ratio 1.973, 95% confidence interval 1.334−2.920; P = .001). There were no statistically significant differences in the risk of new-incident cerebral microbleeds between the rosuvastatin and placebo groups or between APOE ε4 carriers and non-ε4 carriers. There were no significant interactions between rosuvastatin use and APOE ε4 status regarding increased WMH volume (F = 1.020, P = .313) or for new-incident Fazekas scale ≥2 (P = .377), lacunes (P = .232), and microbleeds (P = .362). Conclusions/ImplicationsLow-dose rosuvastatin is an effective and safe therapy for CSVD. The presence of APOE ε4 allele may not be able to predict rosuvastatin treatment outcomes for preventing and/or treating CSVD in older hypertensive patients.

APOE ε4 allele is associated with worse performance in memory dimensions of the mini-mental state examination: the Bambuí Cohort Study of Aging.

This study aimed to investigate the correlation between apolipoprotein E (APOE) ε4 and the mini-mental state examination (MMSE) dimension in an elderly population, using baseline data from the Bambui (Brazil) Cohort Study of Aging. We conducted a community-based cross-sectional study. The study took place at Bambui city, Minas Gerais State, Southeast Brazil. A total of 1408 (87.7%) cohort participants had complete information on the MMSE and health measures. The association between each of five dimensions (concentration, language/praxis, orientation, attention, and memory) underlying the MMSE and APOE ε4 allele was assessed using multivariate linear regression models. Potential confounding variables included sociodemographic factors and selected biomarkers. The main finding is a strong negative association between the presence of APOE ε4 allele and memory dimension in the MMSE (fully adjusted β coefficient = -0.14; 95% confidence interval: -0.27 to -0.04; p = 0.016). No other cognitive dimensions showed significant associations with the APOE ε4 allele. This study is the first to investigate the association between dimensions of the MMSE, obtained from principal component analysis and APOE ε4 carrier status in community-dwelling older adults taking into account a range of potential confounding factors. We found a strong negative association between the presence of APOE ε4 allele and scores on memory dimension of the MMSE, but no effect on other dimensions. Our results reinforce previous data on the literature that APOE ε4 allele has a significant effect on cognitive performance that can be detected even in screening tests, such as the MMSE.

Deposition of tau in the brain in Alzheimer's disease is related to the amount of Aβ40 but not Aβ42(43) deposits and the presence of apolipoprotein E ε4 allele

Introduction: Alzheimer's disease (AD) is characterized by the widespread deposition of amyloid β protein (Aβ) in the form of extracellular plaques and the intracellular accumulation of pathological aggregates of the microtubule associated protein, tau, in the form of neurofibrillary tangles and neuropil threads. We have investigated relationships between the amount of plaque amyloid and tau deposition in brain in sporadic AD and the affect of apolipoprotein E (APOE) genotype on tau load.Material and methods: Wax sections of frontal cortex from 109 cases of late onset AD were immunostained using AT8 antibody to detect deposition of pathological tau proteins. The amount of tau, and Aβ as Aβ40 and Aβ42(43), was quantified by image analysis. The APOE genotype was determined by standard methods.Results: The amount of tau within frontal cortex correlated inversely with patient age but not duration of illness suggesting a more aggressive ‘spread’ of disease into frontal lobes by time of death in younger patients. Tau load correlated (P &lt; 0.001) with Aβ40 but not Aβ42(43) levels, and was also greater in patients with APOE ε4 allele than those without, increasing in line with ε4 allele copy number.Conclusions: Results suggest that tau deposition in late onset AD is favoured in the presence of APOE ε4 allele and when Aβ40 levels are high, the latter also being associated with ε4 allele. Aβ40 is preferentially present in cored plaques where microglial cells are frequent. The amount of tau deposited in the brain in AD may therefore reflect the extent of local neuroinflammatory changes.