Plasma Neurofilament Light and Markers of Sensorimotor Function in a Predominantly Hispanic Population of Older Adults in San Antonio, Texas

Background: Sensorimotor and blood-based biomarkers are promising dementia biomarkers with high accessibility and limited invasiveness. Although sensorimotor changes appear with aging, more severe changes may precede cognitive decline, dementia, and other neurological diseases. Additionally, blood-based neurofilament light (NfL), a broad marker of neuroaxonal injury, is commonly elevated in many types of neurological disease. Prior studies have suggested that increased blood levels of NfL in conjunction with sensorimotor decline may allow for earlier neurological disease diagnosis and/or prediction of disease severity, but little is known about the correlation of these markers in the general population. We examined the association between NfL and sensorimotor markers in a predominantly Hispanic population in San Antonio, Texas. Method: Our sample included older adults from our San Antonio MarkVCID and South Texas Alzheimer’s Disease Research Center (ADRC) cohorts (n=152, mean age 71.2±7.63, 60.4% women, 79.5% Hispanic) with available plasma NfL, olfaction (B-SIT age-adjusted percentile), grip strength, and touch (monofilament) data (Table 1). NfL concentrations were log-transformed to achieve a normal distribution. We used linear or logistic regression models, as appropriate, to assess the association between NfL and sensorimotor outcomes, adjusting for age, sex, race, ethnicity, and cognitive diagnosis. Result: Higher plasma NfL was significantly associated with decreased olfaction score percentiles (Beta [95% Confidence Interval], β=-8.79; [95% CI -16.89; -0.12], p=0.05), grip strength in either hand (left: β=-3.62; [95% CI -5.51; -1.74], p=0.0002; right: β=-2.99; [95% CI -5.01; -1.03], p=0.003), and impaired touch perception (Odds Ratio [95% CI], OR=2.56; [95% CI 1.01; 6.48]; p=0.05), independent of the potential confounders listed above. Conclusion: These results highlight the association of plasma NfL with several markers of sensorimotor function, which may reflect central and peripheral neuroaxonal injury. Additional studies are needed in larger community samples to confirm these findings and explore the potential of NfL as a marker of functional decline in longitudinal studies. We plan to continue collecting these markers, as well as gait and balance, longitudinally to gain a better understanding of the link between neurodegeneration, sensorimotor markers, and neurological disease trajectory in our unique South Texas population

Development of a Panel of Genome-Wide Ancestry Informative Markers to Study Admixture Throughout the Americas

Most individuals throughout the Americas are admixed descendants of Native American, European, and African ancestors. Complex historical factors have resulted in varying proportions of ancestral contributions between individuals within and among ethnic groups. We developed a panel of 446 ancestry informative markers (AIMs) optimized to estimate ancestral proportions in individuals and populations throughout Latin America. We used genome-wide data from 953 individuals from diverse African, European, and Native American populations to select AIMs optimized for each of the three main continental populations that form the basis of modern Latin American populations. We selected markers on the basis of locus-specific branch length to be informative, well distributed throughout the genome, capable of being genotyped on widely available commercial platforms, and applicable throughout the Americas by minimizing within-continent heterogeneity. We then validated the panel in samples from four admixed populations by comparing ancestry estimates based on the AIMs panel to estimates based on genome-wide association study (GWAS) data. The panel provided balanced discriminatory power among the three ancestral populations and accurate estimates of individual ancestry proportions (R2>0.9 for ancestral components with significant between-subject variance). Finally, we genotyped samples from 18 populations from Latin America using the AIMs panel and estimated variability in ancestry within and between these populations. This panel and its reference genotype information will be useful resources to explore population history of admixture in Latin America and to correct for the potential effects of population stratification in admixed samples in the region

Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): bluetongue

A specific concept of strain was developed in order to classify the BTV serotypes ever reported in Europe based on their properties of animal health impact: the genotype, morbidity, mortality, speed of spread, period and geographical area of occurrence were considered as classification parameters. According to this methodology the strain groups identified were (i) the BTV strains belonging to serotypes BTV-1–24, (ii) some strains of serotypes BTV-16 and (iii) small ruminant-adapted strains belonging to serotypes BTV-25, -27, -30. Those strain groups were assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of Article 7, Article 5 on the eligibility of bluetongue to be listed, Article 9 for the categorisation according to disease prevention and control rules as in Annex IV and Article 8 on the list of animal species related to bluetongue. The assessment has been performed following a methodology composed of information collection, expert judgement at individual and collective level. The output is composed of the categorical answer, and for the questions where no consensus was reached, the different supporting views are reported. The strain group BTV (1–24) can be considered eligible to be listed for Union intervention as laid down in Article 5(3) of the AHL, while the strain group BTV-25–30 and BTV-16 cannot. The strain group BTV-1–24 meets the criteria as in Sections 2 and 5 of Annex IV of the AHL, for the application of the disease prevention and control rules referred to in points (b) and (e) of Article 9(1) of the AHL. The animal species that can be considered to be listed for BTV-1–24 according to Article 8(3) are several species of Bovidae, Cervidae and Camelidae as susceptible species; domestic cattle, sheep and red deer as reservoir hosts, midges insect of genus Culicoides spp. as vector species

Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): bluetongue

A specific concept of strain was developed in order to classify the BTV serotypes ever reported in Europe based on their properties of animal health impact: the genotype, morbidity, mortality, speed of spread, period and geographical area of occurrence were considered as classification parameters. According to this methodology the strain groups identified were (i) the BTV strains belonging to serotypes BTV-1–24, (ii) some strains of serotypes BTV-16 and (iii) small ruminant-adapted strains belonging to serotypes BTV-25, -27, -30. Those strain groups were assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of Article 7, Article 5 on the eligibility of bluetongue to be listed, Article 9 for the categorisation according to disease prevention and control rules as in Annex IV and Article 8 on the list of animal species related to bluetongue. The assessment has been performed following a methodology composed of information collection, expert judgement at individual and collective level. The output is composed of the categorical answer, and for the questions where no consensus was reached, the different supporting views are reported. The strain group BTV (1–24) can be considered eligible to be listed for Union intervention as laid down in Article 5(3) of the AHL, while the strain group BTV-25–30 and BTV-16 cannot. The strain group BTV-1–24 meets the criteria as in Sections 2 and 5 of Annex IV of the AHL, for the application of the disease prevention and control rules referred to in points (b) and (e) of Article 9(1) of the AHL. The animal species that can be considered to be listed for BTV-1–24 according to Article 8(3) are several species of Bovidae, Cervidae and Camelidae as susceptible species; domestic cattle, sheep and red deer as reservoir hosts, midges insect of genus Culicoides spp. as vector species

Effect of Ecological Group Classification Schemes on Performance of the AMBI Benthic Index in US Coastal Waters

The AZTI Marine Biotic Index (AMBI) requires less geographically-specific calibration than other benthic indices, but has not performed as well in US coastal waters as it has in the European waters for which it was originally developed. Here we examine the extent of improvement in index performance when the Ecological Group (EG) classifications on which AMBI is based are derived using local expertise. Twenty-three US benthic experts developed EG scores for each of three regions in the United States, as well as for the US as a whole. Index performance was then compared using: (1) EG scores specific to a region, (2) national EG scores, (3) national EG scores supplemented with standard international EG scores for taxa that the US experts were not able to make assignments, and (4) standard international EG scores. Performance of each scheme was evaluated by diagnosis of condition at pre-defined good/bad sites, concordance with existing local benthic indices, and independence from natural environmental gradients. The AMBI performed best when using the national EG assignments augmented with standard international EG values. The AMBI using this hybrid EG scheme performed well in differentiating apriori good and bad sites (\u3e80% correct classification rate) and AMBI scores were both concordant and correlated (rs = 0.4–0.7) with those of existing local indices. Nearly all of the results suggest that assigning the EG values in the framework of local biogeographic conditions produced a better-performing version of AMBI. The improved index performance, however, was tempered with apparent biases in score distribution. The AMBI, regardless of EG scheme, tended to compress ratings away from the extremes and toward the moderate condition and there was a bias with salinity, where high quality sites received increasingly poorer condition scores with decreasing salinity

Development of a panel of genome-wide ancestry informative markers to study admixture throughout the Americas.

Most individuals throughout the Americas are admixed descendants of Native American, European, and African ancestors. Complex historical factors have resulted in varying proportions of ancestral contributions between individuals within and among ethnic groups. We developed a panel of 446 ancestry informative markers (AIMs) optimized to estimate ancestral proportions in individuals and populations throughout Latin America. We used genome-wide data from 953 individuals from diverse African, European, and Native American populations to select AIMs optimized for each of the three main continental populations that form the basis of modern Latin American populations. We selected markers on the basis of locus-specific branch length to be informative, well distributed throughout the genome, capable of being genotyped on widely available commercial platforms, and applicable throughout the Americas by minimizing within-continent heterogeneity. We then validated the panel in samples from four admixed populations by comparing ancestry estimates based on the AIMs panel to estimates based on genome-wide association study (GWAS) data. The panel provided balanced discriminatory power among the three ancestral populations and accurate estimates of individual ancestry proportions (R² > 0.9 for ancestral components with significant between-subject variance). Finally, we genotyped samples from 18 populations from Latin America using the AIMs panel and estimated variability in ancestry within and between these populations. This panel and its reference genotype information will be useful resources to explore population history of admixture in Latin America and to correct for the potential effects of population stratification in admixed samples in the region

Validation of the AIMs panel compared to ancestry estimates using GWAS data.

<p>Validation of the AIMs panel compared to ancestry estimates using GWAS data.</p

Time since admixture for Mestizo and African descendent populations.

<p>Time since admixture for Mestizo and African descendent populations.</p

Performance of nested subsets of AIMs.

<p>Performance of nested subsets of AIMs.</p