APOE Allele Frequencies Research Articles

Alzheimer Disease Associated Loci: APOE Single Nucleotide Polymorphisms in Marmara Region.

Alzheimer's disease (AD) is a major global health challenge, especially among individuals aged 65 or older. According to population health studies, Turkey has the highest AD prevalence in the Middle East and Europe. To accurately determine the frequencies of common and rare APOE single nucleotide polymorphisms (SNPs) in the Turkish population residing in the Marmara Region, we conducted a retrospective study analyzing APOE variants in 588 individuals referred to the Bursa Uludag University Genetic Diseases Evaluation Center. Molecular genotyping, clinical exome sequencing, bioinformatics analysis, and statistical evaluation were employed to identify APOE polymorphisms and assess their distribution. The study revealed the frequencies of APOE alleles as follows: ε4 at 9.94%, ε2 at 9.18%, and ε3 at 80.68%. The gender-based analysis in our study uncovered a tendency for females to exhibit a higher prevalence of mutant genotypes across various SNPs. The most prevalent haplotype observed was ε3/ε3, while rare APOE SNPs were also identified. These findings align with global observations, underscoring the significance of genetic diversity and gender-specific characteristics in comprehending health disparities and formulating preventive strategies.

APOE ε4 Allele Frequency Among Cognitively Healthy Members of an Ojibwe Tribal Nation.

APOE ε4 frequency varies by geography and ancestry. We provide data regarding the frequency of this allele in the Ojibwe people, the fifth largest Indigenous people in the United States. Population study including 33 cognitively normal older individuals of an Ojibwe Tribal Nation (total population: 984; all with ≥25% Ojibwe ancestry). APOE ε4 allele frequency was 19.7%, which is comparable with other cognitively normal American Indian, Alaskan Native, and non-Hispanic White populations of the United States and Europe, with the exception of a lower frequency among Choctaw Nation of Oklahoma participants with >50% American Indian ancestry. While some global populations have very low APOE ε4 prevalence, this allele appears common among American Indian Tribal Nations included thus far in the United States. Because APOE ε4 is a cornerstone for novel diagnostics and therapeutics for Alzheimer disease (AD), future study is warranted to understand ancestry-dependent effects of APOE ε4 on AD risk and biology.

Sex Moderates the Association Between Age and Myelin Water Fraction in the Cingulum and Fornix among Older Adults Without Dementia:A Preliminary Study

AbstractBackgroundCognitive decline in normal aging and Alzheimer’s disease (AD) has been associated with changes in cerebral white matter tracts. Although women are at higher risk of developing AD, studies investigating the effect of sex on white matter integrity have been mixed. Decreased white matter integrity in limbic pathways including the fornix and cingulum have been reported in AD although underlying mechanisms and potential sex differences remain understudied. We explored sex as a moderator of the effect of age on myelin water fraction (MWF), a measure of myelin content, in older adults.MethodFifty‐two older adults without dementia (mean age = 72; 61% female) underwent neuropsychological evaluation and 3T MRI at two research sites. Multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) quantified MWF in three a priori regions of interest including the fornix, cingulum in the hippocampal formation (CGH), and cingulum in the cingulate gyrus (CGC). The California Verbal Learning Test‐Second Edition assessed learning and long‐delay free recall. Separate multiple linear regressions assessed for (1) interactions between age and sex on regional MWF and (2) associations of regional MWF and memory. All models adjusted for APOE e4 allele frequency, vascular risk, and site; the second analysis additionally adjusted for age and sex.Result(1) There was a significant ageXsex interaction for CGC MWF (p = 0.006) and fornix MWF (p = 0.016) (see Figure) but not CGH MWF (p = 0.443). Specifically, for both interactions, in women but not men, as age increased, MWF decreased. (2) Fornix MWF was associated with memory (p = 0.002), but MWF of the two cingulum regions were not (p>0.05). Results did not change when adjusting for hippocampal volume.ConclusionResults suggest that the relationship between age and myelin content of limbic fiber pathways depends on sex, with women but not men showing age‐related decreases. Additionally, and consistent with previous studies, we observed an association between fornix MWF and learning and memory. Understanding sex differences in MWF may facilitate earlier detection of AD risk for women. Longitudinal study with larger samples is needed to further clarify the role sex plays in limbic system myelin integrity and potentially inform interventions.

Native Hawaiians and Pacific Islanders: Is APOE a Biomarker of Disease?

AbstractBackgroundNative Hawaiians and Pacific Islanders (NHPI) are among the least represented racial groups in Alzheimer’s disease (AD) research (for example, there are only 18 samples in the NACC). The prevalence of AD is unknown in NHPIs. Likewise, no large studies have reported disease biomarkers, including assessing APOE genotypes for correlation with AD. In one small study in Guam natives, APOE ε4 was not correlated with AD. We have enrolled 648 NHPIs in our cohort with AD8 and CDR scores, and results of their performance on the NACC neuropsychological battery. We collected APOE genotypes for 234 individuals.MethodBrain health events were held to recruit study participants. Biological samples (saliva or blood) were collected at these events then transported to our lab where DNA was extracted and analyzed to determine APOE genotypes.ResultTable 1 summarizes the cognitive assessments and APOE genotypes for 234 individuals. APOE allele frequencies vary widely based on race. However, in our dataset, the ε4 frequency in NHPI females and males is the same and higher than reported in other races.We are underpowered to detect significant trends in subjects with and without dementia (Table 2). Our preliminary data reveal ε4 allele frequencies in subjects with and without dementia. No trend towards ε4 differences in impaired versus normal subjects.ConclusionWe are augmenting and refining the existing cohort. We are genotyping APOE in 414 additional NHPIs and formally diagnosing each subject. We will have sufficient samples to determine whether or not APOE correlates with AD status. If APOE is not a biomarker of AD in NHPIs, this suggests that the genetic architecture of AD in NHPIs is unique and demonstrates the importance of prioritizing NHPIs in future AD research.

Association of the APOE gene variants with depression in type 2 diabetes.

The risk of depression among patients with diabetes is higher than the general population. The exact mechanisms linking these two diseases are mostly unknown. Energy metabolism disorders seem to be a shared pathway. One of the key genes playing important roles in energy metabolism-related pathways is the APOE gene. We aimed to investigate the association of the APOE gene variants with depression among Iranian patients with type 2 diabetes (T2DM). Three APOE gene alleles and genotypes frequencies (E2, E3, E4) were determined in 244 patients with T2DM (114 with depression and 130 without depression) using the high-resolution melting (HRM) method on the genomic DNA extracted from the patient's peripheral blood. Apoe4 allele frequency was significantly higher in T2DM patients without depression compared with those with depression (11.9 vs. 2.2%, p-value < 0.0001 and p-value = 0.001, respectively). Conversely, the wild allele apoe3 frequency was significantly higher in T2DM patients with depression (86% vs., 69%, p-value < 0.0001). Apoe4 carrier status was associated with decreased risk of depression in patients with T2DM [OR: 0.19 (0.07-0.53)]. Our results showed that the apoe4 allele and apoe4 carrier status significantly reduced the risk of depression among patients with T2DM. Further studies are needed to unravel the complex role of the APOE gene in depression among patients with diabetes.

Applicability of an actuarial neuropsychological method to diagnose mild cognitive impairment in a diverse sample

AbstractBackgroundThe Jak/Bondi actuarial neuropsychological method for detection of mild cognitive impairment (MCI) has been shown to identify subjects less likely to revert to normal and more likely to have Alzheimer’s Disease (AD) biomarkers compared to conventional clinical methods. Various iterations of this method have been applied to datasets of predominately White, highly‐educated participants, limiting generalizability to more diverse cohorts. This project investigated the applicability of the actuarial MCI diagnostic method to the Texas Alzheimer’s Research and Care Consortium (TARCC) cohort.MethodAll subjects from the TARCC cohort with expert consensus diagnoses of normal control (NC) and MCI at baseline (n = 1911; 65.72% female; 47.11% Hispanic; Mage = 67.49; Medu = 12.80) were re‐classified as NC or MCI using actuarial criteria of 2 impaired (&gt;1 SD below normative mean) tests in any of 4 cognitive domains OR 1 impaired test in at least 3 cognitive domains. The clinically‐diagnosed MCI (MCIc) sample (n = 655; 58.47% female; 42.44% Hispanic; Mage = 71.34; Medu = 13.01) and the actuarially‐diagnosed MCI (MCIa) sample (n = 837; 71.21% female; 68.82% Hispanic; Mage = 66.30; Medu = 10.87) were separately submitted to cluster analysis. McNemar’s test was used to investigate frequency of APOE4 allele by diagnostic group.ResultCluster analysis of the MCIa group yielded 3 distinct clusters: a purely amnestic cluster (n = 332), a primary language‐impaired cluster (n = 381), and a multidomain/mixed cluster (n = 124). The MCIc group yielded 2 clusters: a multidomain/mixed cluster (n = 538), and a cognitively normal cluster (n = 117). The MCIc cases were significantly more likely to have APOE4 alleles (33% vs. 28% of MCIa group).ConclusionSimilar to previous research, the MCIa group fell into 3 distinct cognitively‐impaired groups. Despite 18% of MCIc participants falling in a “cognitively‐normal” cluster, MCIc subjects were more likely to have the AD biomarker APOE4. These findings warrant further investigation, particularly in relation to ethnicity, as individuals of Hispanic origin are less likely to carry APOE4 alleles, and APOE4 confers less AD risk in Hispanics compared to non‐Hispanic Whites. Future research will investigate the prognostic utility of the actuarial method for racial/ethnic minorities using cognitive and functional longitudinal data.

APOE Allele Frequency in Southern Greece: Exploring the Role of Geographical Gradient in the Greek Population

the apolipoprotein e4 allele (APOE4) constitutes an established genetic risk factor for Alzheimer's Disease Dementia (ADD). We aimed to explore the frequency of the APOE isoforms in the Greek population of Southern Greece. peripheral blood from 175 Greek AD patients, 113 with mild cognitive impairment (MCI), and 75 healthy individuals. DNA isolation was performed with a High Pure PCR Template Kit (Roche), followed by amplification with a real-time qPCR kit (TIB MolBiol) in Roche's Light Cycler PCR platform. APOE4 allele frequency was 20.57% in the ADD group, 17.69% in the MCI group, and 6.67% in the control group. APOE3/3 homozygosity was the most common genotype, while the frequency of APOE4/4 homozygosity was higher in the AD group (8.60%). APOE4 carrier status was associated with higher odds for ADD and MCI (OR: 4.49, 95% CI: [1.90-10.61] and OR: 3.82, 95% CI: [1.59-9.17], respectively). this study examines the APOE isoforms and is the first to report a higher APOE frequency in MCI compared with healthy controls in southern Greece. Importantly, we report the occurrence of the APOE4 allele, related to ADD, as amongst the lowest globally reported, even within the nation, thus enhancing the theory of ethnicity and latitude contribution.

Genetic risk scores and dementia risk across different ethnic groups in UK Biobank.

Genetic Risk Scores (GRS) for predicting dementia risk have mostly been used in people of European ancestry with limited testing in other ancestry groups. We conducted a logistic regression with all-cause dementia as the outcome and z-standardised GRS as the exposure across diverse ethnic groups. There was variation in frequency of APOE alleles across ethnic groups. Per standard deviation (SD) increase in z-GRS including APOE, the odds ratio (OR) for dementia was 1.73 (95%CI 1.69-1.77). Z-GRS excluding APOE also increased dementia risk (OR 1.21 per SD increase, 95% CI 1.18-1.24) and there was no evidence that ethnicity modified this association. Prediction of secondary outcomes was less robust in those not of European ancestry when APOE was excluded from the GRS. z-GRS derived from studies in people of European ancestry can be used to quantify genetic risk in people from more diverse ancestry groups. Urgent work is needed to include people from diverse ancestries in future genetic risk studies to make this field more inclusive.

Cognitive Reserve Moderates the Association Between Cerebral Blood Flow and Language Performance in Older Adults with Mild Cognitive Impairment

AbstractBackgroundIt has consistently been demonstrated that individuals with higher cognitive reserve (CR) exhibit decreased risk for dementia, and differences in cerebral blood flow (CBF) among those with higher CR may offer a protective mechanism against the cognitive changes associated with dementia. We sought to investigate CR as a moderator of the effect of CBF on memory and language performance in patients with mild cognitive impairment (MCI) and those who are cognitively unimpaired (CU).MethodOlder adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI; N = 46 MCI, 101 CU) underwent neuropsychological evaluation and arterial spin labeling MRI, which was used to quantify CBF in a priori regions. Estimated VIQ from the American National Adult Reading Test was used as a CR proxy. Multiple linear regressions assessed for (1) effect of CR on cognition, (2) effect of CR on CBF, and (3) interaction between CR and CBF on cognition. Cognitive outcomes included memory (word list) and language (category fluency, naming). All models adjusted for age, gender, APOE e4 allele frequency, and education, and interactions additionally adjusted for baseline FDG and pulse pressure.ResultVIQ was not associated with memory but was positively associated with fluency and naming in both groups (ps&lt;0.005). VIQ was not associated with CBF in either group. Individuals with MCI showed a significant interaction between VIQ and CBF on fluency across several regions, including the bilateral hippocampus (p = 0.003), bilateral inferior temporal gyrus (p = 0.008), superior frontal gyrus (p = 0.005), and inferior frontal gyrus (p&lt;0.001). For all models, as CR increased, the magnitude of the association between CBF and performance increased. These interactions were not significant in the CU group. Models with naming or memory as the outcome variable were not significant in either group. Results remained similar when education was not adjusted for.ConclusionThese results suggest that among individuals with MCI, the association between CBF and category fluency is dependent on CR, even after adjusting for several factors. Specifically, higher CR may serve as a protective factor against the negative effect of CBF reductions on fluency. Further research is needed to clarify the role that CR plays as a moderator of CBF and cognition.

APOE E4 is associated with impaired self-declared cognition but not disease risk or age of onset in Nigerians with Parkinson’s disease

The relationship between APOE polymorphisms and Parkinson’s disease (PD) in black Africans has not been previously investigated. We evaluated the association between APOE polymorphic variability and self-declared cognition in 1100 Nigerians with PD and 1097 age-matched healthy controls. Cognition in PD was assessed using the single item cognition question (item 1.1) of the MDS-UPDRS. APOE genotype and allele frequencies did not differ between PD and controls (p > 0.05). No allelic or genotypic association was observed between APOE and age at onset of PD. In PD, APOE ε4/ε4 conferred a two-fold risk of cognitive impairment compared to one or no ε4 (HR: 2.09 (95% CI: 1.13–3.89; p = 0.02)), while APOE ε2 was associated with modest protection against cognitive impairment (HR: 0.41 (95% CI 0.19–0.99, p = 0.02)). Of 773 PD with motor phenotype and APOE characterized, tremor-dominant (TD) phenotype predominated significantly in ε2 carriers (87/135, 64.4%) compared to 22.2% in persons with postural instability/gait difficulty (PIGD) (30/135) and 13.3% in indeterminate (ID) (18/135, 13.3%) (p = 0.037). Although the frequency of the TD phenotype was highest in homozygous ε2 carriers (85.7%), the distribution of motor phenotypes across the six genotypes did not differ significantly (p = 0.18). Altogether, our findings support previous studies in other ethnicities, implying a role for APOE ε4 and ε2 as risk and protective factors, respectively, for cognitive impairment in PD.

Frequencies and Distribution of APOE Gene Polymorphisms and Its Association With Lipid Parameters in the Senegalese Population.

BackgroundApolipoprotein E is a multifunctional protein that plays an important role in lipid metabolism. It is encoded by the APOE gene. However, APOE gene polymorphism has not been very well studied in the Senegalese population. Therefore, we studied allele frequencies, genotype distributions, and the relationship between APOE gene polymorphisms and lipid parameters in the Senegalese women population.MethodologyThis study included 110 healthy women aged 35-72 years. The mean age was 49.8 ± 8.1 years. For all subjects, lipid parameters were analyzed from fasting serum, and APOE genotypes were identified by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) based analysis.ResultsVariations in the frequencies and distribution of the APOE alleles and genotypes were observed (ε3: 47.3%; ε2: 43.2%; ε4: 9.6%; and ε2/ε3: 70%; ε2/ε4: 16.4%; ε3/ε3: 10.9%; ε2/ε4: 2.7%). Compared to the ε3ε3 genotype carriers, carriers of the ε3ε4 genotype had a significantly higher rate of total cholesterol (p=0.03) and no high-density lipoprotein-cholesterol (p=0.02). Univariate analysis showed that the APOE ε4 allele increases the low-density lipoprotein-cholesterol rate (OR=3.06; 95% CI: 1.16-8.22; p=0.02).ConclusionOur study has shown a difference in APOE allele frequencies and genotype distributions with a total absence of ε2ε2 and ε4ε4 genotypes in a sample of Senegalese women. We also found that APOE gene polymorphism might play a role in plasma lipid levels.

Correlation of plasma and neuroimaging biomarkers in Alzheimer's disease.

Blood‐based phosphorylated tau (Ptau) 181 and 217 biomarkers are sensitive and specific for Alzheimer's disease. In this racial/ethnically diverse cohort study, participants were classified as biomarker positive (Ptau+) or negative (Ptau‐) based on Ptau 181 and 217 concentrations and as cognitively impaired (Sym) or unimpaired (Asym). The four groups, Ptau‐/Asym, Ptau+/Asym, Ptau‐/Sym, and Ptau+/Sym, differed by age, APOE‐4 allele frequency, total tau, neurofilament light chain, and cortical thickness measured by MRI. Our results add to increasing evidence that plasma Ptau 181 and 217 concentrations are valid Alzheimer's disease biomarkers in diverse populations.

Dementia Incidence, APOE Genotype, and Risk Factors for Cognitive Decline in Aboriginal Australians

Aboriginal Australians are disproportionately affected by dementia, with incidence in remote populations approximately double that of non-Indigenous populations. This study aimed to identify dementia incidence and risk factors in Aboriginal Australians residing in urban areas, which are currently unknown. A population-based cohort of Aboriginal Australians ≥60 years of age was assessed at baseline and 6-year follow-up. Life-course risk factors (baseline) were examined for incident dementia or mild cognitive impairment (MCI) through logistic regression analyses; adjustments were made for age. APOE genotyping was available for 86 people. Data were included from 155 participants 60 to 86 years of age (mean 65.70 years, SD 5.65 years; 59 male). There were 16 incident dementia cases (age-standardized rate 35.97/1,000 person-years, 95% confidence interval [CI] 18.34-53.60) and 36 combined incident MCI and dementia cases. Older age (odds ratio [OR] 2.29, 95% CI 1.42-3.70), male sex (OR 4.14, 95% CI 1.60-10.77), unskilled work history (OR 5.09, 95% CI 1.95-13.26), polypharmacy (OR 3.11, 95% CI 1.17-8.28), and past smoking (OR 0.24, 95% CI 0.08-0.75) were associated with incident MCI/dementia in the final model. APOE ε4 allele frequency was 24%; heterozygous or homozygous ε4 was associated with incident MCI/dementia (bivariate OR 3.96, 95% CI 1.25-12.50). These findings provide evidence for higher dementia incidence in Aboriginal Australians from urban areas, where the majority of Aboriginal people reside. This study also sheds light on sociodemographic, health, and genetic factors associated with incident MCI/dementia at older ages in this population, which is critical for targeted prevention strategies.

Don’t forget about tau: the effects of ApoE4 genotype on Alzheimer’s disease cerebrospinal fluid biomarkers in subjects with mild cognitive impairment—data from the Dementia Competence Network

ApoE4, the strongest genetic risk factor for Alzheimer’s disease (AD), has been shown to be associated with both beta-amyloid (Aβ) and tau pathology, with the strongest evidence for effects on Aβ, while the association between ApoE4 and tau pathology remains inconsistent. This study aimed to investigate the associations between ApoE4 with CSF Aβ42, total tau (t-tau), phospho-tau181 (p-tau), and with the progression of decline in a large cohort of MCI subjects, both progressors to AD and other dementias, as well as non-progressors. We analyzed associations of CSF Aβ42, p-tau and t-tau with ApoE4 allele frequency cross-sectionally and longitudinally over 3 years of follow-up in 195 individuals with a diagnosis of MCI-stable, MCI-AD converters and MCI progressing to other dementias from the German Dementia Competence Network. In the total sample, ApoE4 carriers had lower concentrations of CSF Aβ42, and increased concentrations of t-tau and p-tau compared to non-carriers in a gene dose-dependent manner. Comparisons of these associations stratified by MCI-progression groups showed a significant influence of ApoE4 carriership and diagnostic group on all CSF biomarker levels. The effect of ApoE4 was present in MCI-stable individuals but not in the other groups, with ApoE4 + carriers having decreased CSF Aβ 42 levels, and increased concentration of t-tau and p-tau. Longitudinally, individuals with abnormal t-tau and Aβ42 had a more rapid progression of cognitive and clinical decline, independently of ApoE4 genotype. Overall, our results contribute to an emerging framework in which ApoE4 involves mechanisms associated with both CSF amyloid-β burden and tau aggregation at specific time points in AD pathogenesis.

Objective subtle cognitive decline is associated with a more rapid increase in plasma phosphorylated‐tau181 levels over time

AbstractBackgroundEarly identification of Alzheimer’s disease (AD) is imperative for early intervention and planning. Objectively‐defined subtle cognitive decline (Obj‐SCD) criteria, based on sensitive neuropsychological scores, is associated with AD biofluid and neuroimaging markers as well as progression to mild cognitive impairment (MCI) and dementia. However, the relationship between Obj‐SCD and newer plasma markers, such as plasma phosphorylated‐tau181 (p‐tau181), is unknown. Therefore, we examined baseline and longitudinal plasma p‐tau181 across CN, Obj‐SCD, and MCI groups.Method953 Alzheimer’s Disease Neuroimaging Initiative participants without dementia had plasma p‐tau181 data, which were log‐transformed prior to analyses. Participants were classified as CN (n=403), Obj‐SCD (n=200), or MCI (n=350) based on actuarial neuropsychological criteria. Baseline analyses compared p‐tau181 across groups. Linear mixed effects models, adjusting for age, sex, APOE e4 allele frequency, and pulse pressure, examined 4‐year p‐tau181 rate of change in Obj‐SCD and MCI participants relative to CN. Follow‐up analyses examined whether the group p‐tau181 x time trajectories differed by Aβ‐PET positivity status.ResultCN and Obj‐SCD groups had lower baseline plasma p‐tau181 than the MCI group and did not differ from one another (Figure 1). However, longitudinally, the Obj‐SCD group had the steepest increase in plasma p‐tau181 over four years and was the only group to differ from CN participants (Figure 2; b=.016, 95% CI: .003‐.018, p=.016). When groups were split by Aβ status, only the Aβ‐negative Obj‐SCD group showed a slightly faster increase in p‐tau181 relative to the Aβ‐negative CN group (b=.019, 95% CI: .001‐.037, p=.044).ConclusionBaseline plasma p‐tau181 did not differ between CN and Obj‐SCD; however, consistent with prior findings, Obj‐SCD was associated with future pathologic changes, including those measured by plasma p‐tau181, prior to frank impairment associated with MCI. Importantly, these results do not appear to be driven by Aβ+ Obj‐SCD participants. Despite the long‐held assumption that cognitive changes invariably follow biomarker changes, these findings suggest that early neuropsychological difficulties may emerge before or in tandem with measurable changes in plasma markers. Future work will examine the prognostic impact of combining Obj‐SCD and plasma markers, which both have the potential to be accessible early markers of future AD‐related declines.

Distinct conformers of amyloid beta accumulate in the neocortex of patients with rapidly progressive Alzheimer's disease

Amyloid beta (Aβ) deposition in the neocortex is a major hallmark of Alzheimer's disease (AD), but the extent of deposition does not readily explain phenotypic diversity and rate of disease progression. The prion strain–like model of disease heterogeneity suggests the existence of different conformers of Aβ. We explored this paradigm using conformation-dependent immunoassay (CDI) for Aβ and conformation-sensitive luminescent conjugated oligothiophenes (LCOs) in AD cases with variable progression rates. Mapping the Aβ conformations in the frontal, occipital, and temporal regions in 20 AD patients with CDI revealed extensive interindividual and anatomical diversity in the structural organization of Aβ with the most significant differences in the temporal cortex of rapidly progressive AD. The fluorescence emission spectra collected in situ from Aβ plaques in the same regions demonstrated considerable diversity of spectral characteristics of two LCOs—quatroformylthiophene acetic acid and heptaformylthiophene acetic acid. Heptaformylthiophene acetic acid detected a wider range of Aβ deposits, and both LCOs revealed distinct spectral attributes of diffuse and cored plaques in the temporal cortex of rapidly and slowly progressive AD and less frequent and discernible differences in the frontal and occipital cortex. These and CDI findings indicate a major conformational diversity of Aβ accumulating in the neocortex, with the most notable differences in temporal cortex of cases with shorter disease duration, and implicate distinct Aβ conformers (strains) in the rapid progression of AD.

Формирование адаптивных типов как микроэволюционный процесс

The study populations have been grouped into two clusters. The first constituted the ethnic groups that are anthropologically affine but differ in adaptive types and husbandry practices. The second included the anthropologically unrelated ethnic groups having similar environment economy systems and adaptive types. We analyzed the genotype and allele frequencies of the metabolism-associated APOE, LCT, TREH, UCP1 genes, and Fok1 and BsmI polymorphisms of VDR gene. A total of 749 samples in the study represents the ethnic groups of Komi-Permyaks (n=181), Komi (n=235), Komi-Izhems (n=200), Shores (n=133). Results. A resemblance in the morphological and physiological complexes that have convergently developed in the course of environmental adaptations have been shown to reflect similarities in the gene features of anthropologically unrelated populations. In contrast, in the historically related groups that have utilized different biotopes and types of husbandry, there are growing divergence in the frequencies of metabolism-associated genotypes and alleles. These findings imply that ecological adaptations of modern human populations drive the minor changes in allele frequencies, which have occurred over a few generations. Conclusion. The apparent morpho-physiological and population-genetic specificity of the adaptive types allows us to regard the process of their formation as microevolution.

Cognitive changes in patient living with HIV-AIDS and apolipoprotein-E polymorphism: is there an association?

Patients with HIV-AIDS treated with antiretroviral drugs still have high prevalence of cognitive disorders and many factors are likely to contribute for ongoing neurologic decline such as chronic low-level infection, coinfections with hepatitis B and C and genetic influences, both the virus and the host. Some evidences suggest that the genetic APOE polymorphism may be an associated risk factor. This study aimed to evaluate the association between APOE polymorphisms and cognitive disorders in patients with HIV-AIDS.This was a cross-sectional study comprising 133 patients aged 19-59years old, with HIV-AIDS and were assisted at the infectious disease outpatient clinics at Hospital Universitário Oswaldo Cruz, in Recife, Brazil. For cognitive evaluation, Mini-Mental State Examination test (MMSE) and Montreal Cognitive Assessment test (MoCA) were used. The determination of APOE gene polymorphism was performed by using the PCR-RFLP technique.Sociodemographic and clinical characteristics were not significantly associated to APOE ε4 polymorphism, except for the high results of CD4 rate (p < 0.015). There was an absence associated between APOE ε4 polymorphism and neurocognitive tests.This study found no association between cognitive alterations and APOE polymorphism in patients with HIV-AIDS in the Northeast of Brazil. The imbalance of APOE allelic frequency distribution, according to Hardy-Weinberg law, there could be an adjustment phase of its equilibrium suffered by the HIV virus, however, the mechanism is still unknown.

Plasma cholesterol in Alzheimer's disease and frontotemporal dementia.

BackgroundThe relationship between the apolipoprotein E (APOE)-ε4 allele, triglyceride (TG) level, and cholesterol level and an increased risk of developing Alzheimer’s disease (AD) has been well established, but their relationship with behavioral-variant frontotemporal dementia (bvFTD) is not well-known.MethodologyThe levels of TGs, total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein were measured in bvFTD and AD patients and in normal controls (NCs). DNA was extracted, and APOE was genotyped.ResultsThe APOE-ε4 allele frequency was higher in the AD group than in the NC group, but no difference was found between the AD and the bvFTD groups. The bvFTD group had higher LDL than the AD group, and significant differences were also found for the cholesterol level in the dementia groups compared with the NC group. Elevated LDL level was positively correlated with appetite and eating score in the bvFTD group. Compared with the AD patients and NCs without the APOE-ε4 allele, those with the APOE-ε4 allele had higher TC, but its correlation with the bvFTD group was absent.ConclusionsThe bvFTD and the AD groups had higher cholesterol levels. The APOE-ε4 allele and eating behavior might modify lipid metabolism in dementia. TG and cholesterol analyses may offer a new opportunity for targeted treatments.

Amyloid PET in Dementia Syndromes: A Chinese Multicenter Study.

Cerebral β-amyloid deposits and regional glucose metabolism assessed by PET are used to distinguish between Alzheimer disease (AD) and other dementia syndromes. In the present multicenter study, we estimated the prevalence of β-amyloid deposits on PET imaging in a wide variety of dementia syndromes and mild cognitive impairment (MCI) within a memory clinic population. Methods: Of the 1,193 consecutive patients with cognitive impairment (CI) who received 1 11C-PIB PET or 18F-AV45 PET or both 11C-PIB PET and 18F-AV45 PET, 960 were diagnosed with AD, 36 with frontotemporal dementia (FTD), 5 with dementia with Lewy bodies, 144 with MCI, 29 with vascular dementia, 4 with corticobasal syndrome, and 15 with unclassifiable dementia. Baseline clinical diagnoses were independently established without access to PET imaging results. Apolipoprotein E (ApoE) genotype analysis was performed on CI patients and 231 sex- and age-matched controls. Results: Of the 1,193 CI patients, 860 (72.1%) were amyloid-positive. The prevalence of amyloid positivity in AD and MCI patients was 86.8% (833/960) and 9.7% (14/144), respectively. In FTD patients, the prevalence of β-amyloid deposits was 5.6% (2/36). In the 4 corticobasal syndrome patients, 2 were amyloid-positive. Three of the 5 patients with dementia with Lewy bodies showed amyloid positivity, as did 6 of the 29 vascular dementia (20.7%) patients. The ApoEε4 allele frequency was significantly increased in amyloid-positive CI patients (30.5%) as compared with other amyloid-negative CI patients (14%) or controls (7.3%). Conclusion: Amyloid imaging may potentially be the most helpful parameter for differential diagnosis in dementia, particularly to distinguish between AD and FTD. Amyloid PET can be used in conjunction with the ApoEε4 allele genetic risk test for amyloid deposits.