Comparing biological markers of Alzheimer\u27s disease across blood fraction and platforms: Comparing apples to oranges

Introduction: This study investigated the comparability of potential Alzheimer\u27s disease (AD) biomarkers across blood fractions and assay platforms. Methods: Nonfasting serum and plasma samples from 300 participants (150 AD patients and 150 controls) were analyzed. Proteomic markers were obtained via electrochemiluminescence or Luminex technology. Comparisons were conducted via Pearson correlations. The relative importance of proteins within an AD diagnostic profile was examined using random forest importance plots. Results: On the Meso Scale Discovery multiplex platform, 10 of the 21 markers shared \u3e50% of the variance across blood fractions (serum amyloid A R2 = 0.99, interleukin (IL)10 R2 = 0.95, fatty acid-binding protein (FABP) R2 = 0.94, I309 R2 = 0.94, IL-5 R2 = 0.94, IL-6 R2 = 0.94, eotaxin3 R2 = 0.91, IL-18 R2 = 0.87, soluble tumor necrosis factor receptor 1 R2 = 0.85, and pancreatic polypeptide R2 = 0.81). When examining protein concentrations across platforms, only five markers shared \u3e50% of the variance (beta 2 microglobulin R2 = 0.92, IL-18 R2 = 0.80, factor VII R2 = 0.78, CRP R2 = 0.74, and FABP R2 = 0.70). Discussion: The current findings highlight the importance of considering blood fractions and assay platforms when searching for AD relevant biomarkers

A blood-based biomarker panel indicates IL-10 and IL-12/23p40 are jointly associated as predictors of β-amyloid load in an AD cohort

Alzheimer\u27s Disease (AD) is the most common form of dementia, characterised by extracellular amyloid deposition as plaques and intracellular neurofibrillary tangles of tau protein. As no current clinical test can diagnose individuals at risk of developing AD, the aim of this project is to evaluate a blood-based biomarker panel to identify individuals who carry this risk. We analysed the levels of 22 biomarkers in clinically classified healthy controls (HC), mild cognitive impairment (MCI) and Alzheimer\u27s participants from the well characterised Australian Imaging, Biomarker and Lifestyle (AIBL) study of aging. High levels of IL-10 and IL-12/23p40 were significantly associated with amyloid deposition in HC, suggesting that these two biomarkers might be used to detect at risk individuals. Additionally, other biomarkers (Eotaxin-3, Leptin, PYY) exhibited altered levels in AD participants possessing the APOE ϵ4 allele. This suggests that the physiology of some potential biomarkers may be altered in AD due to the APOE ϵ4 allele, a major risk factor for AD. Taken together, these data highlight several potential biomarkers that can be used in a blood-based panel to allow earlier identification of individuals at risk of developing AD and/or early stage AD for which current therapies may be more beneficial

Fluctuations in Blood Biomarkers of Head Trauma in NCAA Men’s Soccer Athletes over the Course of a Season

Repetitive subconcussive impacts to the head are commonplace in soccer. The ability to detect the extent of neurological injury due to these impacts over the course of a season is paramount. PURPOSE: The purpose of the current study was to examine alterations in blood biomarkers of head injury over the course of a soccer season. METHODS: Sixteen National Collegiate Athletic Association (NCAA) male soccer athletes participated in weekly blood sampling throughout an 18-week season. Athlete statistics were received from the coaches post-season. Serum samples were stored at -80°C until analysis for Tau and Neurofilament Light polypeptide (NFL) using a QuanterixTM Simoa HD-1 analyzer. We used R statistical language and the lme4 statistical package to perform a linear mixed effects analysis of the relationships of minutes played (MP) and headers (HEAD) with Tau and NFL. We included the intercept for subjects as a random effect, and time point (TP), MP and HEAD (without the interaction term) as fixed effects. P-values for model comparisons were obtained by likelihood ratio tests. RESULTS: NFL was significantly elevated in weeks 5 (7.3±2.8pg/mL; pCONCLUSION: In our study, neither MP nor HEAD were significant predictors for Tau concentration over the course of an NCAA Men’s soccer season. HEAD appeared to have a small predictive effect on NFL concentrations across the season. Research reported in this publication was supported (in part) by the National Institute on Aging of the National Institutes of Health under Award Numbers R01AG051848, R01AG058537, and R01AG058252. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health

A Depressive Endophenotype Of Poorer Cognition Among Cognitively Healthy Community-dwelling Adults: Results From The Western Australia Memory Study

Objective: The objective was to evaluate in a cognitively normal population the utility of an endophenotype of the depression–cognition link previously shown to be related to cognitive functioning in mild cognitive impairment and Alzheimer\u27s disease. Methods: The data of 460 cognitively normal adults aged 32–92 years (M = 63.5, standard deviation = 9.24) from the Western Australian Memory Study with the Cross-national comparisons of the Cambridge Cognitive Examination-revised (CAMCOG-R) scores and 30-item Geriatric Depression Scale (GDS) scores were analyzed to determine the relationship between the five-item depressive endophenotype (DepE) scale drawn from the GDS and level of performance on a measure of cognitive functioning. Results: For the entire sample, there was a nonsignificant trend toward a negative relationship between DepE and CAMCOG-R scores. When analyzed for those 65 years and older, there was a significant negative relationship between the two measures (p = 0.001) with DepE scores significantly increasing the risk for performing more poorly on the CAMCOG-R (odds ratio = 1.53). Analysis of data for those 70 years and older showed that DepE was the only predictor significantly related to poorer CAMCOG-R performance (p = 0.001). For the 70 years and older group, DepE scores significantly increased the risk of poorer CAMCOG-R scores (odds ratio = 2.23). Analysis of the entire sample on the basis of ApoEε4 carrier status revealed that DepE scores were significantly negatively related only to ApoEε4 noncarrier regardless of age. Conclusions: Elevated DepE scores are associated with poor neuropsychological performance among cognitively normal older adults. Use of the DepE may allow for the identification of a subset of older adults where depression is a primary factor in cognitive decline and who may benefit from antidepressant therapies

Biomarkers of Alzheimer\u27s Disease Among Mexican Americans

Background: Mexican Americans are the fastest aging segment of the U.S. population, yet little scientific literature exists regarding the Alzheimer\u27s disease (AD) among this segment of the population. The extant literature suggests that biomarkers of AD will vary according to race/ethnicity though no prior work has explicitly studied this possibility. The aim of this study was to create a serum-based biomarker profile of AD among Mexican American. Methods: Data were analyzed from 363 Mexican American participants (49 AD and 314 normal controls) enrolled in the Texas Alzheimer\u27s Research & Care Consortium (TARCC). Non-fasting serum samples were analyzed using a luminex-based multi-plex platform. A biomarker profile was generated using random forest analyses. Results: The biomarker profile of AD among Mexican Americans was different from prior work from non-Hispanic populations with regards to the variable importance plots. In fact, many of the top markers were related to metabolic factors (e.g., FABP, GLP-1, CD40, pancreatic polypeptide, insulin-like-growth factor, and insulin). The biomarker profile was a significant classifier of AD status yielding an area under the receiver operating characteristic curve, sensitivity, and specificity of 0.77, 0.92, and 0.64, respectively. Combining biomarkers with clinical variables yielded a better balance of sensitivity and specificity. Conclusion: The biomarker profile for AD among Mexican American cases is significantly different from that previously identified among non-Hispanic cases from many large-scale studies. This is the first study to explicitly examine and provide support for blood-based biomarkers of AD among Mexican Americans. Areas for future research are highlighted

Innovative diagnostic tools for early detection of Alzheimer\u27s disease

Current state-of-the-art diagnostic measures of Alzheimer\u27s disease (AD) are invasive (cerebrospinal fluid analysis), expensive (neuroimaging) and time-consuming (neuropsychological assessment) and thus have limited accessibility as frontline screening and diagnostic tools for AD. Thus, there is an increasing need for additional noninvasive and/or cost-effective tools, allowing identification of subjects in the preclinical or early clinical stages of AD who could be suitable for further cognitive evaluation and dementia diagnostics. Implementation of such tests may facilitate early and potentially more effective therapeutic and preventative strategies for AD. Before applying them in clinical practice, these tools should be examined in ongoing large clinical trials. This review will summarize and highlight the most promising screening tools including neuropsychometric, clinical, blood, and neurophysiological tests

Author Correction: Genetic meta-analysis of diagnosed Alzheimer\u27s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.

An amendment to this paper has been published and can be accessed via a link at the top of the paper