Epsilon4 Allele Of Apolipoprotein Research Articles

The pathogenic implication of abnormal interaction between apolipoprotein E isoforms, amyloid-beta peptides, and sulfatides in Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia in the aging population. Prior work has shown that the epsilon4 allele of apolipoprotein E (apoE4) is a major risk factor for "sporadic" AD, which accounts for >99% of AD cases without a defined underlying mechanism. Recently, we have demonstrated that sulfatides are substantially and specifically depleted at the very early stage of AD. To identify the mechanism(s) of sulfatide loss concurrent with AD onset, we have found that: (1) sulfatides are specifically associated with apoE-associated particles in cerebrospinal fluid (CSF); (2) apoE modulates cellular sulfatide levels; and (3) the modulation of sulfatide content is apoE isoform dependent. These findings not only lead to identification of the potential mechanisms underlying sulfatide depletion at the earliest stages of AD but also serve as mechanistic links to explain the genetic association of apoE4 with AD. Moreover, our recent studies further demonstrated that (1) apoE mediates sulfatide depletion in amyloid-beta precursor protein transgenic mice; (2) sulfatides enhance amyloid beta (Abeta) peptides binding to apoE-associated particles; (3) Abeta42 content notably correlates with sulfatide content in CSF; (4) sulfatides markedly enhance the uptake of Abeta peptides; and (5) abnormal sulfatide-facilitated Abeta uptake results in the accumulation of Abeta in lysosomes. Collectively, our studies clearly provide a link between apoE, Abeta, and sulfatides in AD and establish a foundation for the development of effective therapeutic interventions for AD.

Apolipoprotein epsilon4 allele and psoriasis severity

Editor, I read the recent paper by Choi et al. [1] with a great interest. Coto-Segura et al. [2] concluded that ‘‘The APOE-epsilon4 allele could be a risk factor for developing a severe form of psoriasis.’’ Indeed, the correlation between APOE-epsilon4 allele and medical disorder is widely studied. The report by Coto-Segura et al. seems to be a pioneer piece of work in dermatology on psoriasis. However, there are some points on the studies by Coto-Segura et al. to be concerned. First, although the number of cases and controls in this study seems statistically appropriate, the actual prevalence of a polymorphism might need more subjects, thousands of included cases, for verification. This is an important basic error in genome wide association case/control studies [5]. Second, the race and ethnic effect of the subjects is another point to be concerned for making a conclusion of the finding. The difference of APOEepsilon4 allele distributions among different populations is confirmed in medical literature and this might lead to difference in its relationship to specific medical disorders. The good examples are those controversial reports on Alzheimer’s disease [1, 3, 4]. These points need clarification to strengthen the conclusion of the work.

Cholesterol metabolism and transport in the pathogenesis of Alzheimer’s disease

Alzheimer's disease (AD) is the most common neurodegenerative disorder, affecting millions of people worldwide. Apart from age, the major risk factor identified so far for the sporadic form of AD is possession of the epsilon4 allele of apolipoprotein E (APOE), which is also a risk factor for coronary artery disease (CAD). Other apolipoproteins known to play an important role in CAD such as apolipoprotein B are now gaining attention for their role in AD as well. AD and CAD share other risk factors, such as altered cholesterol levels, particularly high levels of low density lipoproteins together with low levels of high density lipoproteins. Statins--drugs that have been used to lower cholesterol levels in CAD, have been shown to protect against AD, although the protective mechanism(s) involved are still under debate. Enzymatic production of the beta amyloid peptide, the peptide thought to play a major role in AD pathogenesis, is affected by membrane cholesterol levels. In addition, polymorphisms in several proteins and enzymes involved in cholesterol and lipoprotein transport and metabolism have been linked to risk of AD. Taken together, these findings provide strong evidence that changes in cholesterol metabolism are intimately involved in AD pathogenic processes. This paper reviews cholesterol metabolism and transport, as well as those aspects of cholesterol metabolism that have been linked with AD.

Lack of Association of the APOE ε4 Allele with the Risk of Obstructive Sleep Apnea: Meta-Analysis and Meta-Regression

Reports on the association of polymorphisms in the gene encoding apolipoprotein E (APOE)--a vital macromolecule in cholesterol metabolism--with obstructive sleep apnea (OSA) have provided conflicting results. Our objective was to meta-analytically synthesize the existing evidence for the association of the APOE epsilon4 allele with the risk of OSA. Random effects meta-analysis and meta-regression. Genetic epidemiological studies reporting the association of APOE epsilon4 allele with OSA susceptibility. Synthesis of APOE epsilon4 allele data from 6,508 subjects including 1,901 cases of OSA and 4,607 controls. None. Eight studies were included in the random effects meta-analysis; the summary effect size measured as odds ratio (OR) for association of the APOE epsilon4 allele with the risk of OSA was found to be 1.13 (95% confidence interval 0.86-1.47). There was a statistically significant heterogeneity (I2 = 72%, P = 0.001) across study results that was not explained by the mean age, proportion of males, or the proportion possessing the APOE epsilon4 allele or when grouped based on the geographic location of the study. The hypothesis that the APOE epsilon4 allele may be causally associated with OSA cannot be supported on the basis of published literature.

Is ApoE ε4 Associated with Cognitive Functioning in African Americans Diagnosed with Alzheimer Disease? An Exploratory Study

The effect of the apolipoprotein epsilon4 allele (ApoE epsilon4) on cognitive performance in patients with probable Alzheimer disease (AD) has been studied in primarily Caucasian samples. The aim of this exploratory study was to examine whether the presence of ApoE epsilon4 is associated with cognitive performance in African American AD patients. A cross-sectional, retrospective design was used to address the study objective. Data were extracted from the records of 65 African American patients who participated in the National Institutes of Health-National Institute on Aging (NIH-NIA) Emory University Alzheimer Disease Center Registry. Inclusion criteria were a clinical diagnosis of probable AD, cognitive testing using the Mattis Dementia Rating Scale and the Consortium to Establish a Registry for Alzheimer Disease (CERAD) neuropsychological battery, and ApoE genotyping. Seventy percent of the patients were ApoE epsilon4 positive. Multiple regression analyses indicated that ApoE epsilon4 was significantly associated with poorer design copying (CERAD Constructional Praxis subtest), but other significant relationships were not observed between positive epsilon4 status and cognitive performance. These preliminary findings suggest that the ApoE epsilon4 allele is not strongly associated with a particular pattern of cognitive functioning in African Americans once they are diagnosed with AD. However, these findings require replication in a large prospectively recruited and population-based sample of African American AD patients before firm conclusions can be reached.

Disclosure of APOE genotype for risk of Alzheimer's disease.

The apolipoprotein E (APOE) genotype provides information on the risk of Alzheimer's disease, but the genotyping of patients and their family members has been discouraged. We examined the effect of genotype disclosure in a prospective, randomized, controlled trial. We randomly assigned 162 asymptomatic adults who had a parent with Alzheimer's disease to receive the results of their own APOE genotyping (disclosure group) or not to receive such results (nondisclosure group). We measured symptoms of anxiety, depression, and test-related distress 6 weeks, 6 months, and 1 year after disclosure or nondisclosure. There were no significant differences between the two groups in changes in time-averaged measures of anxiety (4.5 in the disclosure group and 4.4 in the nondisclosure group, P=0.84), depression (8.8 and 8.7, respectively; P=0.98), or test-related distress (6.9 and 7.5, respectively; P=0.61). Secondary comparisons between the nondisclosure group and a disclosure subgroup of subjects carrying the APOE epsilon4 allele (which is associated with increased risk) also revealed no significant differences. However, the epsilon4-negative subgroup had a significantly lower level of test-related distress than did the epsilon4-positive subgroup (P=0.01). Subjects with clinically meaningful changes in psychological outcomes were distributed evenly among the nondisclosure group and the epsilon4-positive and epsilon4-negative subgroups. Baseline scores for anxiety and depression were strongly associated with post-disclosure scores of these measures (P<0.001 for both comparisons). The disclosure of APOE genotyping results to adult children of patients with Alzheimer's disease did not result in significant short-term psychological risks. Test-related distress was reduced among those who learned that they were APOE epsilon4-negative. Persons with high levels of emotional distress before undergoing genetic testing were more likely to have emotional difficulties after disclosure. (ClinicalTrials.gov number, NCT00571025.)

Associations between stroke risk and cognition in normal aging and Alzheimer's disease with and without depression

Stroke risk factors have been increasingly implicated in the development of age-related cognitive decline, the spectrum of vascular cognitive impairment, and, more recently, Alzheimer's disease (AD). In addition, depression and the apolipoprotein (APOE) epsilon4 allele have been reported to influence the association between stroke risk and cognition. However, few studies have described the relations among stroke risk, cognition, and APOE genotype in AD, and the findings have been equivocal. Thirty cognitively normal older adults, 30 AD patients with depression, and 30 AD patients without depression were administered a comprehensive neuropsychological battery measuring several domains including memory, attention, language, visuospatial skills, executive functions, and speed of information processing. The Framingham Stroke Risk Profile (FSRP), a validated scale that was developed to predict 10-year probability of stroke, was used to quantify stroke risk burden. AD patients with depression demonstrated greater stroke risk burden relative to the cognitively normal group and, across all participants, increased stroke risk was associated with poorer performance on memory and processing speed measures. Moreover, stroke risk accurately predicted AD diagnosis. Notably, there were no significant differences in stroke risk or cognitive performance between the AD participants with depression and those without depression. Given that many markers of stroke risk are modifiable or treatable, our findings have implications for assessment, prevention, and treatment of cognitive decline.

Plasma β‐amyloid and duration of Alzheimer's disease in adults with Down syndrome

To investigate the relation of plasma levels of Abeta peptides (Abeta1-40 and Abeta1-42) and apolipoprotein E (APOE) genotype to dementia status, and the duration of Alzheimer's disease (AD) in adults with Down syndrome (DS). Adults with DS were recruited from community settings and followed up for a mean period of 6.7 years. Plasma levels Abeta1-40 and Abeta1-42 and APOE genotype were determined at the last visit. There were 83 nondemented participants and 44 participants with prevalent AD. Overall, plasma levels of Abeta1-42, Abeta1-40 and the ratio Abeta1-42/Abeta1-40 did not differ significantly between the adults with DS. Among demented participants, the mean level of Abeta1-40 was significantly lower (157.0 vs. 195.3) and the ratio of Abeta1-42/Abeta1-40 was significantly higher (0.28 vs. 0.16) in those with more than 4 years duration of dementia than in those with 4 or fewer years' duration of dementia. This pattern was generally similar in those with and without an APOE epsilon4 allele. There is an association between plasma Abeta peptide levels and the duration of AD in older persons with DS. The predictive and diagnostic roles of Abeta1-42 and Abeta1-40 measurements for AD, however, remain controversial. Change in Abeta peptide levels with onset of AD and with the duration of dementia may account for a lack of difference between prevalent cases and nondemented individuals and for variation in the predictive power of Abeta peptide levels.

Meta-Analysis of Alzheimer's Disease Risk with Obesity, Diabetes, and Related Disorders

Late-onset Alzheimer's disease (AD) is a multifactorial and heterogeneous disorder with major risk factors including advanced age, presence of an apolipoprotein E epsilon4 (APOE4) allele, and family history of AD. Other risk factors may be obesity and diabetes and related disorders, which are highly prevalent. We reviewed longitudinal epidemiological studies of body mass, diabetes, metabolic syndrome, and glucose and insulin levels on risk for AD. We conducted meta-analyses of the results from these studies. For obesity assessed by body mass index, the pooled effect size for AD was 1.59 (95% confidence interval [CI] 1.02-2.5; z = 2.0; p = .042), and for diabetes, the pooled effect size for AD was 1.54 (95% CI 1.33-1.79; z = 5.7; p < .001). Egger's test did not find significant evidence for publication bias in the meta-analysis for obesity (t = -1.4, p = .21) or for diabetes (t = -.86, p = .42). Since these disorders are highly comorbid, we conducted a meta-analysis combining all studies of obesity, diabetes, and abnormal glucose or insulin levels, which yielded a highly significant pooled effect size for AD of 1.63 (95% CI 1.39-1.92; z = 5.9; p < .001). Obesity and diabetes significantly and independently increase risk for AD. Though the level of risk is less than that with the APOE4 allele, the high prevalence of these disorders may result in substantial increases in future incidence of AD. Physiological changes common to obesity and diabetes plausibly promote AD.

Brain MRI, Apoliprotein E Genotype, and Plasma Homocysteine in American Indian Alzheimer Disease Patients and Indian Controls

We obtained brain MRIs, plasma homocysteine levels and apolipoprotein E genotyping for 11 American Indian Alzheimer disease (AD) subjects and 10 Indian controls. We calculated white matter hyperintensity volume (WMHV), whole brain volume (WBV), and ratio of white matter hyperintensity volume to whole brain volume (WMHV/WBV). There were no significant differences between AD subjects and controls in gender, history of hypertension, diabetes, or history of high cholesterol, but hypertension and diabetes were more common among AD subjects. There was no difference between AD and control groups in age (range for all subjects was 61-89 years), % Indian heritage, waist size or body mass index. Median Indian heritage was 50% or greater in both groups. Range of education was 5-13 years in the AD group and 12-16 years in controls. Median plasma homocysteine concentration was higher in AD subjects (11 micromol/L vs. 9.8 micromol/L), but did not achieve statistical significance. Significantly more AD subjects had apolipoprotein Eepsilon4 alleles than did controls (63% vs.10%). Neuroimaging findings were not significantly different between the 2 groups, but AD subjects had greater WMHV (median 15.64 vs. 5.52 cc) and greater WMHV/WBV ratio (median 1.63 vs. 0.65 %) and a far greater range of WMHV. In combined AD subjects and controls, WBV correlated with BMI and age. WMHV and WMHV/WBV correlated inversely with MMSE scores (p = 0.001, 0.002, respectively). In addition, WMHV correlated positively with % Indian heritage (p = 0.047).

Apolipoprotein E genotype is related to nitric oxide production in platelets

The presence of the epsilon4 allele of apolipoprotein E (APOE) is considered a risk factor for sporadic Alzheimer's disease (AD). Our recent data demonstrated that the systemic modulation of oxidative stress in platelets and erythrocytes is disrupted in aging and AD. In this study, the relationship between APOE genotype and oxidative stress markers, both in AD patients and controls, was evaluated. The AD group showed an increase in the content of thiobarbituric acid-reactive substances (TBARS) and in the activities of nitric oxide synthase (NOS) and Na, K-ATPase, when compared to controls. Both groups had a similar cGMP content and superoxide dismutase activity. APOE epsilon4 allele carriers showed higher NOS activity than non-carriers. These results suggest a possible influence of APOE genotype on nitric oxide (NO) production that might enhance the effects of age-related specific factor(s) associated with neurodegenerative disorders.

Apolipoprotein E ɛ4 influences on episodic recall and brain structures in aging pilots

The apolipoprotein (APOE) epsilon4 allele is associated with cognitive deficits and hippocampal atrophy in nondemented middle-aged and older adults. It is not known to what extent this genetic risk factor for Alzheimer's disease (AD) impacts performance in late middle-aged and older workers in cognitively demanding occupations. This cross-sectional analysis examines brain-cognitive-genetic relationships in actively flying general aviation pilots, half of whom are APOE epsilon4 carriers. Fifty pilots were studied with structural MRI and memory tasks. Average visual paired associate memory recall performance was lower in APOE epsilon4 carriers than non-carriers. Memory performance correlated positively with hippocampal volume, but no structural differences were found in hippocampal or frontal volumes with respect to APOE epsilon4 allele. These results were evident in healthy professionals without any presenting memory problems and without selection for a family history of AD. These findings point to basic memory testing as a sensitive tool for detecting APOE epsilon4-related influences on memory in aging workers.

The Apolipoprotein E ϵ4 Allele is not Associated With Cognitive Dysfunction in Cardiac Surgery

The plasma protein apolipoprotein E (APOE) is a risk factor for degenerative cognitive decline manifested by mild cognitive impairment and later by Alzheimer's disease. Patients undergoing coronary artery bypass grafting (CABG) are known to have a high prevalence of preexisting cognitive impairment and postoperative cognitive dysfunction. Because both mild cognitive impairment and Alzheimer's disease generally occur in elderly individuals, the age group that commonly present for CABG, we investigated if the APOE epsilon4 allele was associated with patients manifesting preexisting cognitive impairment and postoperative cognitive dysfunction. The DNA of 282 patients who had undergone neuropsychologic testing before and 3 and 12 months after CABG was analyzed for APOE genotype. Patients were classified as having preexisting cognitive impairment if cognitive function was decreased in two or more tests compared with a healthy control group. Postoperative cognitive dysfunction was defined as a decrease in two or more tests compared with the group mean baseline score. The APOE epsilon4 allele was found in 83 (29.4%) patients. Although preexisting cognitive impairment was present in 105 (37.2%) and postoperative cognitive dysfunction in 33 (12%) and 31 (11%) at 3 and 12 months postoperatively, there was no relationship with the presence of the APOE epsilon4 allele or any of the six genotypes. Preexisting cognitive impairment and postoperative cognitive dysfunction are not associated with APOE epsilon4 genotype, suggesting that cognitive impairment both before and after CABG may not be associated with degenerative cognitive decline.

Synergistic effect of apolipoprotein E ε4 and butyrylcholinesterase K-variant on progression from mild cognitive impairment to Alzheimer's disease

To evaluate the synergistic effects of the apolipoprotein E (APOE) epsilon4 and butyrylcholinesterase K-variant (BCHE-K) alleles on progression to Alzheimer's disease (AD) in individuals with mild cognitive impairment (MCI). This was a post-hoc exploratory analysis from a 3-4-year, randomized, placebo-controlled study of rivastigmine in participants with MCI (InDDEx study). Participants who consented to genetic testing were included in the current analyses. The incidence of progression to AD, cognitive decline and changes in MRI brain volumes were investigated in participants from the placebo arm of the InDDEx study. Of the 1018 participants in the overall study, 464 were successfully genotyped for both APOE and butyrylcholinesterase. Of these, 68 (14.7%) carried > or =1 APOE epsilon4 and > or =1 BCHE-K allele. The presence of APOE epsilon4 was associated with a significantly higher incidence of progression to AD whereas the presence of BCHE-K had no independent effect on progression. A synergistic effect of the combined presence of APOE epsilon4 and BCHE-K on the time to clinical diagnosis of AD and on MRI brain volumes was seen. Progression to AD and hippocampal volumetric loss was greatest in participants who carried both APOE epsilon4 and BCHE-K alleles and lowest in BCHE-K carriers without the APOE epsilon4 allele. In MCI, the risk of cognitive decline, hippocampal volumetric loss and progression to AD seems to be the greatest in individuals who carry at least one copy of both the BCHE-K and APOE epsilon4 alleles.

Sleep‐Disordered Breathing and Cognition in Older Women

To investigate the association between objectively measured sleep-disordered breathing (SDB) and cognitive impairment in community-dwelling older women and to determine whether the apolipoprotein E (APOE) epsilon4 allele modifies this association. Cross-sectional. Participants' homes and two sites of the Study of Osteoporotic Fractures (SOF). Four hundred forty-eight women with a mean age+/-standard deviation (SD) of 82.8+/-3.4. Participants completed the Mini-Mental State Examination (MMSE), Trail Making Test Part B (Trails B), and polysomnography (PSG). SDB indices were the apnea-hypopnea index (AHI), the central apnea index (CAI), and oxygen saturation (SaO2) nadir less than 80%. APOE epsilon4 was determined for a subset of 242 women. Cognitive impairment was defined as 1.5 SDs or more from the sample mean on either cognitive test (MMSE or Trails B). All SDB indices were associated with cognitive impairment according to the MMSE (AHI (per SD, odds ratio (OR)=1.4, 95% confidence interval (CI)=1.03-1.9), AHI of > or = 30 (OR=3.4, 95% CI=1.4-8.1), SaO2 nadir < 80% (OR=2.7, 95% CI=1.1-6.6), and CAI (per SD, OR=1.4, 95% CI=1.1-1.7)). Weaker, nonsignificant associations emerged between SDB and Trails B. In women who completed genotyping, each SD increase in AHI was associated with 70% greater odds of cognitive impairment according to the MMSE (OR=1.7, 95% CI=1.2-2.6). Women with the epsilon4 allele had a nearly five times greater odds of impairment (per SD, OR=4.6, 95% CI-1.0-20.7); the association was smaller and nonsignificant in women without the epsilon4 allele (per SD, OR=1.5, 95% CI-0.9-2.4; P for interaction=.08). SDB is an important risk factor for cognitive impairment in older women, especially those with the APOE epsilon4 allele. Mechanisms linking these disorders need to be identified.

Apolipoprotein E Genotype and Response of Carbon Monoxide Poisoning to Hyperbaric Oxygen Treatment

Hyperbaric oxygen (HBO2) reduced the incidence of cognitive sequelae 6 weeks after carbon monoxide (CO) poisoning compared with normobaric oxygen (NBO2). The apolipoprotein (APOE) epsilon4 allele predicts unfavorable neurologic outcome after brain injury and stroke. To assess the effects of the epsilon4 allele on 6-week cognitive sequelae after CO poisoning. We tested APOE genotypes in 86 of 152 CO-poisoned patients from our randomized trial. Logistic regression was used to control for risk factors while testing for effects with the epsilon4 allele or interactions with epsilon4 and treatment on 6-week and 6- and 12-month cognitive sequelae. We enrolled 86 patients: 44 received HBO2 and 42 NBO2 therapy. A total of 31 (36%) patients had at least one epsilon4 allele. Six-week cognitive sequelae rates for patients treated with HBO2 and NBO2, respectively: epsilon4 allele absent, 11% (3/27) and 43% (12/28); epsilon4 allele present, 35% (6/17) and 29% (4/14). The epsilon4 allele was not associated with 6-week cognitive sequelae, 27% (15/55) without and 32% (10/31) with the epsilon4 allele (P = 0.323). The interaction between the epsilon4 allele and treatment was significantly associated with 6-week cognitive sequelae (P = 0.048). The interaction between the epsilon4 allele and treatment was not associated with 6- and 12-month cognitive sequelae. HBO2 therapy reduces cognitive sequelae after CO poisoning in the absence of the epsilon4 allele. Because apolipoprotein genotype is unknown at the time of poisoning, we recommend that patients with acute CO poisoning receive HBO2.

PIB is a non-specific imaging marker of amyloid-beta (A ) peptide-related cerebral amyloidosis

The in vivo imaging probe [11C]-PIB (Pittsburgh Compound B, N-methyl[11C]2-(4'-methylaminophenyl-6-hydroxybenzathiazole) is under evaluation as a key imaging tool in Alzheimer's disease (AD) and to date has been assumed to bind with high affinity and specificity to the amyloid structures associated with classical plaques (CPs), one of the pathological hallmarks of the disease. However, no studies have systematically investigated PIB binding to human neuropathological brain specimens at the tracer concentrations achieved during in vivo imaging scans. Using a combination of autoradiography and histochemical techniques, we demonstrate that PIB, in addition to binding CPs clearly delineates diffuse plaques and cerebrovascular amyloid angiopathy (CAA). The interaction of PIB with CAA was not fully displaceable and this may be linked to the apolipoprotein E-epsilon4 allele. PIB was also found to label neurofibrillary tangles, although the overall intensity of this binding was markedly lower than that associated with the amyloid-beta (Abeta) pathology. The data provide a molecular explanation for PIB's limited specificity in diagnosing and monitoring disease progression in AD and instead indicate that the ligand is primarily a non-specific marker of Abeta-peptide related cerebral amyloidosis.

Differences in the Association Between Apolipoprotein E Genotype and Mortality Across Populations

The gene for apolipoprotein-E (APOE) has three common alleles (epsilon2, epsilon3, and epsilon4) that have been shown to be associated with differences in the risk of death in persons older than 60 years in European populations. However, previous research suggests that they may not be associated with mortality in African Americans, and the evidence in Asians is mixed. It is now possible to examine the effects of these genotypes on mortality in African American, Chinese, Japanese, and Korean populations. The analysis is based on two types of published data: genotype by age and mortality by genotype. Demographic synthesis uses a multistate model to combine data from these case-control and cohort studies to provide maximum likelihood estimates of the relative risks of death. In general, the APOE epsilon2 allele is associated with 5%-10% lower mortality than the epsilon3/3 genotype. The epsilon4/4 allele is generally associated with a moderately high relative risk of death. The epsilon3/4 genotype is associated with 22% excess risk in Europeans and U.S. whites and with about 35% in Chinese. However, there is no evidence of excess risk with epsilon3/4 among African Americans and little excess risk among Japanese and Koreans. The relationship between genotype and mortality is consistent within these ethnic groups. For example, the estimates of R(3/4) for Japanese in Japan and Hawaii are both low, and the estimates for Chinese in Taiwan and Shanghai are relatively high. . The relationship between APOE genotype and mortality differs across population groups but shows little evidence of variation within groups.

Association of genetic variants of ABCA1 with Alzheimer's disease risk

ABCA1 plays key roles in cholesterol transport and apolipoprotein E (APOE) metabolism in the brain. To evaluate the relationship between ABCA1 genetic variants and Alzheimer's disease (AD), independently or in concert with the APOE epsilon4 allele, we examined three ABCA1 polymorphisms located in the coding region (R219K, I883M, and R1587K) and two ABCA1 polymorphisms in the promoter region (C-14T and C-477T) in a group of 372 Spanish AD patients and 440 controls. The ABCA1 219K, 883I, 1587R haplotype was significantly associated with AD, conferring a risk of 1.78 (P = 0.007). The ABCA1 C-14T polymorphism modified the risk of AD in an APOE epsilon4 allele-dependent fashion: in APOE epsilon4 carriers, homozygous for the ABCA1 -14T allele had 3.7 times higher risk of developing AD (OR = 13.99) than carriers of the ABCA1 -14CC and CT genotypes (OR = 3.79). These data suggest that the development of AD might be influenced by either a qualitative change of the ABCA1 protein caused by coding region variants (219K, 883I, and 1587R), or by a quantitative change in ABCA1 expression caused by promoter region variant (-14T) in concert with the APOE epsilon4 allele.

The relationship between nutrient intake and cognitive performance in people at risk of dementia

There is evidence of a link between nutrient intake and cognitive impairment and decline in old age. There has been no study of nutrient intake in Irish subjects at risk of dementia. To investigate the possible link between nutrient intake and cognitive performance in a group of Irish adults at risk of dementia, and to compare the nutrient intake in these adults stratified by the absence or presence of the apolipoprotein E (APOE) epsilon4 allele. Forty-four subjects, who were first-degree blood relatives of people with Alzheimer's disease, were recruited. Cognitive performance and nutritional intake were assessed and apolipoprotein E (APOE) genotype determined. The intakes of cholesterol (P < 0.037) and Na (P < 0.037) were significantly higher in subjects with altered cognitive performance. There was no significant difference in nutrient intakes between APOE epsilon-4 allele positive and APOE epsilon-4 allele negative subjects. The findings of this work suggest that dietary cholesterol and sodium intake may be linked to cognitive impairment.