APOE Epsilon4 Research Articles

The apolipoprotein E ɛ4 allele and memory performance in HIV-1 seropositive subjects: differences at baseline but not after acute oral lorazepam challenge

The APOE epsilon4 allele, an established genetic risk factor for late-onset Alzheimer's disease, has been linked to an increased risk for dementia especially in older individuals with HIV-1 infection. This allele has also been associated with increased memory impairment following oral lorazepam challenge in healthy elderly. Lorazepam and other benzodiazepines are widely prescribed in individuals with HIV-1 infection who are at increased risk for cognitive impairment. The aim of this study was to examine if the epsilon4 allele influences lorazepam-induced memory deficits in this population. Forty-one non-demented, HIV-1 seropositive adults (15 epsilon4 carriers, mean age = 43.47 +/- 8.25; 26 epsilon4 non-carriers, mean age = 46.77 +/- 8.56) participated in a double-blind, placebo-controlled crossover design, receiving single acute oral doses of lorazepam 0.5, 1.0 mg, or placebo over three sessions, each 1 week apart. Standardized neuropsychological assessments, including measures of immediate and delayed verbal recall, were conducted at baseline and at 1, 2.5, and 5 h post-drug administration in each condition. Acute lorazepam administration produced dose- and time-dependent impairments in measures of verbal recall. However, the e4 allele did not modulate these adverse effects. An APOE epsilon4 group by time interaction was also found such that the APOE-epsilon4-positive subjects had significantly better immediate and delayed verbal recall than the negative subjects at baseline assessment, but the groups did not significantly differ at any subsequent time point. Future studies should clarify the role of epsilon4 in the modulation of drug-induced cognitive toxicity and baseline performance and their relationship to progressive decline, especially in older individuals with HIV-1 infection, a group at increased risk for dementia.

APOE ɛ4 is associated with postictal confusion in patients with medically refractory temporal lobe epilepsy

This study examined the relationship between the APOE epsilon4 allele and postictal confusion in patients with medically intractable temporal lobe epilepsy (TLE). Patients with at least one epsilon4 allele (n=22) were three times more likely to exhibit postictal confusion (68%) than the 63 patients without epsilon4 (43%). These preliminary results demonstrate that APOE epsilon4 is associated with an increased risk of postictal confusion in patients with medically intractable TLE, suggesting possible dysfunction in neuronal recovery mechanisms.

Alzheimer's disease and vascular dementia in developing countries: prevalence, management, and risk factors

Despite mortality due to communicable diseases, poverty, and human conflicts, dementia incidence is destined to increase in the developing world in tandem with the ageing population. Current data from developing countries suggest that age-adjusted dementia prevalence estimates in 65 year olds are high (>or=5%) in certain Asian and Latin American countries, but consistently low (1-3%) in India and sub-Saharan Africa; Alzheimer's disease accounts for 60% whereas vascular dementia accounts for approximately 30% of the prevalence. Early-onset familial forms of dementia with single-gene defects occur in Latin America, Asia, and Africa. Illiteracy remains a risk factor for dementia. The APOE epsilon4 allele does not influence dementia progression in sub-Saharan Africans. Vascular factors, such as hypertension and type 2 diabetes, are likely to increase the burden of dementia. Use of traditional diets and medicinal plant extracts might aid prevention and treatment. Dementia costs in developing countries are estimated to be US$73 billion yearly, but care demands social protection, which seems scarce in these regions.

Use of statins and incidence of dementia and cognitive impairment without dementia in a cohort study

Evidence of a relation between use of lipid lowering drugs and cognitive outcomes is mixed. This study aimed to test the association between use of statins and incidence of dementia and cognitive impairment without dementia (CIND) over 5 years of follow-up. Data were from a population-based cohort study comprising 1,789 older Mexican Americans. All participants had cognitive and clinical evaluations performed every 12 to 15 months. Participants who fell below specified cutpoints on cognitive tests were then evaluated clinically. Dementia diagnoses were finalized by an adjudication team. A total of 1,674 participants free of dementia/CIND at baseline were included in these analyses. Statin use was verified at each participant's home by medicine cabinet inspection. Cox proportional hazards models were used to evaluate the association between statin use and incidence of dementia/CIND. Overall, 452 of 1,674 participants (27%) took statins at any time during the study. Over the 5-year follow-up period, 130 participants developed dementia/CIND. In Cox proportional hazards models adjusted for education, smoking status, presence of at least one APOE epsilon4 allele, and history of stroke or diabetes at baseline, persons who had used statins were about half as likely as those who did not use statins to develop dementia/CIND (HR = 0.52; 95% CI 0.34, 0.80). Statin users were less likely to have incident dementia/cognitive impairment without dementia during a 5-year follow-up. These results add to the emerging evidence suggesting a protective effect of statin use on cognitive outcomes.

HDL: Close to Our Memories?

The last decade has witnessed an explosion in studies of the role of lipoproteins in brain function. Neurons require a continuous supply of lipids for membrane synthesis and acetylcholine production. Indeed, the brain is a site of intense lipid turnover—even though the central nervous system (CNS) accounts for only 2.1% of body weight, it contains 23% of total body cholesterol.1 Lipid metabolism in the brain is tightly controlled locally, as plasma lipoproteins are shielded from the brain by the blood-brain barrier. Although neuronal cells are capable of de novo synthesis of a wide spectrum of molecular species of lipids, they rely heavily on exogenous sources and readily bind and internalize lipoproteins of the extracellular fluid.2 Equally, neurons need to dispose of excess lipids; lipoprotein-mediated lipid transport is therefore bidirectional and includes cellular efflux of cholesterol.3 See accompanying article on page 1556 Human cerebrospinal fluid (CSF) primarily contains spherical lipoproteins of approximately 10 to 12 nm in diameter with hydrated density in the range 1.063 to 1.25 g/mL, thereby resembling HDL in human plasma.3,4⇓ Lipid concentrations in CSF are however much lower (eg, 300- to 400-fold for total cholesterol and phospholipids) as compared to the plasma compartment.4 Apolipoproteins (apo) E and A-I are the major apolipoproteins in human CSF (typical concentration range: 0.1 to 0.4 mg/dL3,4⇓), with apoA-II, A-IV, J, D, C-II, C-III, C-IV, and H equally present.3,4⇓ Importantly, CSF lipoproteins carry amyloid-β (Aβ), a 39- to 43-aa peptide produced in neuronal cells, which is the major component of senile amyloid plaques.5 The metabolism of CSF lipoproteins remains poorly characterized but seems to be distinct from that of plasma lipoproteins. ApoE-rich HDL are synthesized locally in CNS and secreted by astrocytes as discoidal complexes enriched in free cholesterol.6 High …

Risk Factors for Neurocognitive Dysfunction After Cardiac Surgery in Postmenopausal Women

Women are at higher risk than men for neurologic complications from cardiac operations. This study identified risk factors for neurocognitive dysfunction after cardiac operations in elderly women. One hundred thirteen postmenopausal women undergoing primary coronary artery bypass grafting, with or without valve operation, underwent psychometric testing and neurologic evaluation the day before operation and 4 to 6 weeks postoperatively. Risk factors assessed for neurologic complications included atherosclerosis of the ascending aorta and apolipoprotein epsilon4 genotype. Postoperative neurocognitive dysfunction was defined as the composite end point of a one standard deviation decrement from baseline on two or more psychometric tests or a new neurologic deficit. Neurocognitive dysfunction was present in 25% of the women 4 to 6 weeks postoperatively. Women with a neurocognitive deficit tended to be older than those without a deficit (72.1 +/- 8.1 vs 69.4 +/- 8.9 years, p = 0.144) and were more likely to have mild atherosclerosis of the ascending aorta, a history of congestive heart failure, longer duration of cardiopulmonary bypass (CPB) and aortic cross-clamping, lower nadir blood pressure during CPB, higher rates of postoperative atrial fibrillation, and longer postoperative hospitalization. Mild atherosclerosis of the ascending aorta, duration of CPB, duration of aortic cross-clamping (p = 0.051), and length of postsurgical hospitalization were independently associated with postoperative neurocognitive dysfunction. Mild atherosclerosis of the ascending aorta, duration of CPB, aortic cross-clamping time, and length of hospitalization, but not apolipoprotein epsilon4 genotype, identified risk for neurocognitive dysfunction after cardiac operation in postmenopausal women.

Impact of APOE status on cognitive maintenance in healthy elderly persons

The epsilon4 allele, a variant of the apolipoprotein E (ApoE) gene, is the most prominent genetic risk factor for sporadic, non-familial Alzheimer's disease (AD) currently known. We investigated the impact of the ApoE-epsilon4 status on cognitive performance at repeated test administration in elderly non-symptomatic persons, with a specific focus on practice effects. Three hundred and fifty-five physically and mentally healthy participants of the Basel Study on the Elderly (119 F, 236 M; age 68.3 +/- 7.6; years of education 12.7 +/- 3.1; Mini-Mental State scores 29.0 +/- 1.0) were grouped into ApoE epsilon4 carriers and ApoE epsilon4 non-carriers (36.9% and 63.1% of the sample, respectively). Participants were assessed at the beginning of the longitudinal study and on average two years later by means of the California Verbal Learning Test (CVLT) and the Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery (CERAD-NAB), a multidimensional cognitive test battery. Baseline and change scores were analyzed with multiple regression procedures and adjusted for age, education and gender; change scores were also adjusted for baseline performance. The ApoE epsilon4 non-carriers showed slightly better performance with regard to most cognitive parameters at baseline. Mean practice effects of the ApoE epsilon4 non-carriers in 12 out of 13 CVLT variables and in five out of the nine main CERAD-NAB variables were above the 50th percentile, while those of the ApoE epsilon4 carriers were below the 50th percentile in the respective distributions of test-retest change scores. The epsilon4 allele of the ApoE gene has a negative impact on cognitive performance, notably on episodic memory functions, in physically and mentally healthy aged persons. Practice effects seen in carriers of the ApoE epsilon4 were inferior in most areas tested to the effects seen in ApoE epsilon4 non-carriers. Further follow-up of these subjects will help to determine the clinical significance of these findings.

Does the Apolipoprotein ε4 Allele Predispose Varsity Athletes to Concussion? A Prospective Cohort Study

To determine the association between the apolipoprotein epsilon 4 allele and concussion. We hypothesized that apolipoprotein epsilon 4 carriers may be more likely to sustain a concussion. Prospective cohort study. University of Toronto varsity athletics. Included 318 of 822 collegiate student athletes who participated in University of Toronto varsity sports from September 2002 to April 2006. The presence of apolipoprotein epsilon 4 was described dichotomously after genotyping blood samples collected from participants. Concussions were identified by sport-medicine professionals present on the sidelines using on-field assessment forms. All concussion diagnoses were verified by a sports medicine physician. Survival analysis was used to determine the association between apolipoprotein epsilon 4 and first concussion. The unadjusted hazard ratio for concussion in the apolipoprotein epsilon 4 carriers was 1.18 (95% CI: 0.52, 2.69) compared to noncarriers. Adjustment for sex, weight, height, and team type resulted in a hazard ratio of 1.06 (95% CI: 0.41, 2.72), indicating little effect from confounding factors. There is no important association between carrying the apolipoprotein epsilon 4 allele and sustaining a concussion. At this time, we do not recommend preseason genetic testing for varsity athletes as a mechanism for targeting prevention strategies.

O4-05-03: The apolipoprotein E-epsilon 2 allele is associated with increased Alzheimer neuropathology but preserved cognition: Findings from the 90+ study

O4-05-03: The apolipoprotein E-epsilon 2 allele is associated with increased Alzheimer neuropathology but preserved cognition: Findings from the 90+ study

P1-478: Isoform-specific effects of apolipoprotein E on the stability of Abeta protofibrils

Alzheimer's disease (AD) is characterized by the deposition of amyloid beta peptides (Abeta) as senile plaques. Apolipoprotein E (apoE), one of the lipid transport proteins, co-deposits with senile plaque amyloids in AD brains. Three major alleles of human apoE gene, epsilon2, epsilon3 and epsilon4 have been recognized, of which epsilon4 has been known to be associated with an increased risk for developing AD. Mouse genetic studies by overexpression of human apoE3 and apoE4 in the absence of endogenous apoE showed that the fibrillar Abeta deposits in the hippocampus of apoE4-expressing mice were greater than those in apoE3-expressing mice, suggesting that human apoE4 facilitates amyloid fibril deposition thereby leading to AD. It has been well documented that apoE inhibits Abeta fibril formation in vitro especially in the nucleation phase, although the isoform-specific effects of apoE against Abeta fibrillization has not been well characterized. To evaluate the isoform-specific effects of apoE, we carried out an in vitro Abeta fibrillization assay and investigated the formation of low molecular weight Abeta, protofibrils, and fibrils using thioflavin T fluorescence and size exclusion chromatography. First, we showed that Abeta(1–42) fibrillized faster in the presence of recombinant apoE4 than apoE2 or apoE3, although the affinity of the three isoforms to native Abeta were at similar levels. We next found that apoE2 and apoE3 enhanced the persistence of Abeta protofibrils and delayed the start of Abeta fibril formation, whereas apoE4 did not. We also found that protofibrils comprised of Abeta and apoE3 were more stable than those of Abeta and apoE4. In addition, a SDS-stable 40-kDa band positive both for Abeta and apoE was detected in the Abeta protofibril fraction upon coincubation with apoE2 or apoE3, which was scarcely detected with apoE4. These data suggest that apoE2/3 is involved in the stability of Abeta protofibrils, whereas apoE4 lacks this ability. The isoform-specific effects of apoE on Abeta protofibrils may be one of the determinants for the aggregation and deposition of Abeta in AD brains.

P4-139: Body fat composition and cognitive dysfunction in the elderly Korean

In addition to the association between obesity and cardiovascular disorders, with the presence of a vascular burden as a cofactor, recent studies have particularly focused on the association between indicators of obesity and dementia. A high BMI can increase the risk for dementia when measured before clinical dementia onset. Although the use of BMI in population-based and clinical studies is feasible, this is an index of obesity and shows limits in its ability to distinguish between fat and fat-free mass or between visceral and subcutaneous abdominal fat. Subjects were followed up for about 2 years; 433 persons had BMI data and body fat distribution data by abdominal fat CT analysis. Cognitive function was ascertained using standard methods including K-MMSE and CERAD-K. Cognitive dysfunction was analyzed using follow-up as time to event, adjusting for demographics and apolipoprotein E-epsilon4 status. Compared with subjects in the first quartile of initial BMI, subjects in the third quartile had a lower cognitive dysfunction. For total abdominal fat amount, subjects in the second quartile had a lower cognitive dysfunction. The association between adiposity and cognitive dysfunction resembled a U shape in the elderly Korean. The prospective association between adiposity and cognitive dysfunction differs depending on the body fat distribution. This may explain previous conflicting reports. Larger prospective studies are required to investigate this further.

Cerebrospinal fluid, serum and plasma protein oxidation in Alzheimer’s disease

Many studies have shown differences in carbonylation and nitration of individual proteins in brain and body fluids of Alzheimer's disease (AD) patients. Therefore, we wanted to examine whether total levels of these oxidative stress markers of proteins were altered in AD. Total levels of carbonyls and nitrotyrosine in cerebrospinal fluid, serum and plasma were measured in 22 AD patients and 18 age-matched controls using commercially available enzyme immunoassay kits. Protein carbonylation in cerebrospinal fluid did not differ between AD patients and controls but was decreased in APOE epsilon4 carriers as compared with non-carriers. Serum but not plasma levels of carbonyls tended to be decreased in AD patients as compared with aged controls. Nitrotyrosine concentrations did not differ between the groups. Surrogate cerebrospinal fluid markers for AD, beta-amyloid (1-42) and tau, correlated with blood carbonyl and nitrotyrosine levels. According to these preliminary data, changes in oxidative metabolism related to the pathogenesis of AD cannot be detected as increased cerebrospinal fluid, serum or plasma protein carbonylation or nitration.

CSF β-amyloid 1–42 and tau in Tunisian patients with Alzheimer's disease: The effect of APOE ɛ4 allele

Alzheimer's disease (AD) is the leading cause of dementia. Currently, no definitive diagnostic test for AD exists. An accurate, convenient and objective test to detect AD is urgently needed for efficient drug development and effective clinical use of emerging therapies. The aim of the present work is to investigate the usefulness of cerebrospinal fluid (CSF) beta-amyloid protein (Abeta1-42) and total tau protein (t-tau) analyses in the diagnosis of AD and whether apolipoprotein E (ApoE) epsilon4 allele is a factor for AD affecting Tunisian people. Abeta1-42 and t-tau levels were measured in CSF from AD patients (n=73), non-Alzheimer dementia (nAD, n=35) and healthy controls (HC, n=38) by sandwich enzyme-linked immunosorbent assay. Abeta1-42 levels were decreased and t-tau increased in AD patients. The combination of Abeta1-42 and t-tau at baseline yielded a sensitivity of 87.4% for detection of AD. The specificities were 97.3% for controls and 82.7% for other dementia. The ApoE epsilon4 allele frequency (29.5%) was significantly higher in the AD patients than in the nAD patients (17.1%) or in the control groups (9.5%). AD patients carrying ApoE epsilon4 allele had lower Abeta1-42 (p<0.001) levels than those without a epsilon4 allele. The combination of t-tau and Abeta1-42 is a robust and reliable assay that may be useful in discriminating cases at risk for AD such as ApoE epsilon4 allele carriers from nAD patients or from age-matched control subjects.

Association of Apolipoprotein E Polymorphisms in Patients with Non-Alcoholic Steatohepatitis

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal hepatic steatosis in the absence of alcohol abuse worldwide. Non-alcoholic steatohepatitis (NASH) is the most progressive form of NAFLD. The aim of this study was to investigate the role of apolipoprotein E (APOE) polymorphisms in the development of NASH. We analysed 57 NASH patients and 245 healthy controls using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a case-control study. The diagnosis of the patients was based on liver biopsy. The serum levels of glucose, lipids, vitamin B12, folic acid, homocysteine, insulin, total biluribin, total protein, albumin, ferritin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined in all of the subjects. Body mass index (BMI), waist circumference (WC), AST, ALT, fasting blood sugar (FBS), total cholesterol, triglyceride (TG), low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, insulin and ferritin levels were significantly higher in the 57 patients with NASH compared with the 245 healthy controls. The APOE epsilon3 allele was overrepresented in the whole group of NASH patients (epsilon3=97.37% in NASH versus 82.45% in controls). The APOE polymorphism was statistically significantly associated with NASH (chi(2)=15.741; p=0.008). The APOE3/3 genotype (odds ratio [OR]=7.941; p=0.000) was strongly associated with increased risk for NASH in all NASH patients. Consequently, the APOE3/3 genotype may play a role in the aetiopathogenesis of NASH.

Significant effect of APOE epsilon 4 genotype on the risk of dementia in Alzheimer's disease and mortality in persons with Down Syndrome

Virtually all adults with Down syndrome (DS) have neuropathological manifestations of Dementia in Alzheimer's disease (DAD) but not all develop clinical psychopathology. The effect of allelic variants of Apolipoprotein (APOE) gene in development and progression of DAD and mortality in persons with DS is examined. Recruited participants with DS underwent two to 14 sequential assessments over a follow up period of 6 years on average and their APOE genotype determined. Dementia status was confirmed as recommended by the Working Group for the Establishment of Criteria for the Diagnosis of Dementia in Individuals with Intellectual Disability. APOE genotype results were available for 252 individuals. Participants with APOE epsilon 4 allele had significantly higher risk of developing DAD (HR = 1.8, 95% CI: 1.12-2.79), had an earlier onset of DAD (55.0 vs 57.0 years; p = 0.0027) and a more rapid progression to death compared with participants with epsilon 3 allele (4.2 years vs. 5.4 years, respectively, p = 0.048). In non-demented persons with DS, epsilon 4 allele was associated with earlier death by 17 years (mean survival age, 55.7 vs. 72.7 years; HR = 5.9, 95% CI: 1.7-21.3). This study highlights the relationship of APOE genotype to morbidity and mortality in persons with DS which has important clinical implications. We recommend screening for APOE genotype in persons with DS to identify those at risk of DAD and premature death. Further research is required to investigate the underlying reasons for the early mortality in non-demented DS persons with an epsilon 4 allele.

Association analysis of dynamin‐binding protein (DNMBP) on chromosome 10q with late onset Alzheimer's disease in a large caucasian UK sample

A recent scan of single nucleotide polymorphisms (SNPs) in the region 40-107 Mb on chromosome 10q in a large Japanese case-control cohort identified six SNPs in or near the dynamin-binding protein gene (DNMBP) that were associated with late onset Alzheimer's disease (LOAD) in individuals lacking the APOE epsilon4 allele [Kuwano et al. (2006); Hum Mol Genet 15:2170-2182]. We genotyped these six SNPs in 1,212 unrelated Caucasian patients of UK origin with LOAD and 1,389 ethnically, gender and age matched control subjects. We did not observe a statistically significant association with the risk of LOAD for any of the six SNPs in the sample as a whole. When stratifying the sample by APOE one SNP (intergenic SNP rs11190302) was associated with LOAD in individuals lacking the epsilon4 allele (genotypic P = 0.027, allelic P = 0.066). However this association was in the opposite direction to that detected in the Japanese population. It remains to be determined whether DNMBP is associated with LOAD.

Infection and Alzheimer's Disease: The APOE ε4 Connection and Lipid Metabolism

Microorganisms, bacteria and viruses may infect and cause a range of acute and chronic diseases in humans dependent on the genetic background, age, sex, immune and health status of the host, as well as on the nature, virulence and dose of infectious agent. Late onset Alzheimer's disease (AD) is a progressive neurodegenerative illness of broad aetiology with a strong genetic component and a significant contribution of age, sex and life style factors. Both infectious diseases and AD are characterised by an increased production of an array of immune mediators, cytokines, chemokines and complement proteins by the host cells as well as by changes in the host lipid metabolism. In this review, we re-examine a dangerous liaison between several viral and bacterial infections and the most significant genetic factor for AD, APOE epsilon4, and the possible impact of this alliance on AD development. This connection was discussed in the broader context of lipid metabolism and in the light of different capacity of various infectious agents, their toxic lipophilic products and host lipoprotein particles for binding to cell receptor(s).

APOE epsilon 4 allele predicts faster cognitive decline in mild Alzheimer disease.

To determine whether APOE epsilon 4 predicts rate of cognitive change in incident and prevalent Alzheimer disease (AD). Individuals were recruited from two longitudinal cohort studies-the Washington Heights and Inwood Columbia Aging Project (WHICAP; population-based) and the Predictors Study (clinic-based)--and were followed for an average of 4 years. Three samples of participants diagnosed with AD, with diverse demographic characteristics and baseline cognitive functioning, were studied: 1) 199 (48%) of the incident WHICAP cases; 2) 215 (54%) of the prevalent WHICAP cases; and 3) 156 (71%) of the individuals diagnosed with AD in the Predictors Study. Generalized estimating equations were used to test whether rate of cognitive change, measured using a composite cognitive score in WHICAP and the Mini-Mental State Examination in Predictors, varied as a function of epsilon 4 status in each sample. The presence of at least one epsilon 4 allele was associated with faster cognitive decline in the incident population-based AD group (p = 0.01). Parallel results were produced for the two prevalent dementia samples only when adjusting for disease severity or excluding the most impaired participants from the analyses. APOE epsilon 4 may influence rate of cognitive decline most significantly in the earliest stages of Alzheimer disease.

Genetic analysis of tumor necrosis factor-α (TNF-α) G-308A and Saitohin Q7R polymorphisms with Alzheimer's disease

Neuroinflammation and abnormal phosphorylation of TAU proteins have been implicated in the etiology of Alzheimer's disease (AD). Several studies have suggested the G-308A promoter polymorphism in one of the proinflammatory cytokine genes tumor necrosis factor-alpha (TNF-alpha) encoding TNF-alpha may be associated with AD pathogenesis. Association between the Q7R polymorphism in saitohin (STH), a gene nested within the intron of the Tau gene, has also been reported. To determine whether these two polymorphisms contribute to the risk for late-onset AD (LOAD) in Chinese, we have investigated 207 sporadic LOAD patients and 222 healthy controls. The associations of the AA genotype and A-allele with LOAD (chi(2) = 8.74, df = 1, P = 0.0031, and chi(2) = 4.47, df = 1, P = 0.035) were found. After stratifying by apolipoprotein E allele 4 (APOE epsilon4) status, increased LOAD risks associated with the AA genotype and A-allele only in the APOE epsilon4 non-carriers (chi(2) = 9.21, df = 1, P = 0.002; chi(2) = 10.02, df = 1, P = 0.0015) were seen. These results suggested that the TNF-alpha gene G-308A polymorphism might be a risk factor for LOAD and dependent on APOE epsilon4 status in Chinese. Homozygous Q/Q of STH Q7R polymorphism was the only one genotype found in either LOAD group or controls. No R allele was detected in LOAD and control groups. The extremely rare frequency of the ancestral R allele differs sharply from that observed in studies in the Caucasian population, suggesting obvious ethnic differences.

Total serum cholesterol levels and Alzheimer's dementia in patients with down syndrome

The risk for dementia in Alzheimer's disease (DAD) in adults with Down syndrome (DS) is higher than in the general adult population. Hypercholesterolaemia has been reported as a risk factor for DAD in the general population. This study investigated the role of serum cholesterol levels in the onset of DAD in the DS population. This study investigated total serum cholesterol levels in 179 DS persons (with and without DAD). The possible association between Apolipoprotein E and amyloid beta1-40 and beta1-42 levels was also investigated. No statistically significant association was found between total serum cholesterol levels and dementia in AD or with amyloid beta levels. However for DS adults with an apoE epsilon4 allele significantly higher serum cholesterol levels were found. Hypercholesterolaemia is not a risk factor for DAD in persons with DS. However, DS persons with an apoE epsilon4 allele are susceptible to high serum cholesterol. Such individuals should be screened on a regular basis.