New Gloucester, ME, United States
New Gloucester, ME, United States

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Cummings J.L.,Cleveland Clinic | Geldmacher D.,University of Alabama at Birmingham | Farlow M.,IU Alzheimers Disease and Related Disorders | Sabbagh M.,Sun Diagnostics | And 2 more authors.
CNS Neuroscience and Therapeutics | Year: 2013

Summary: To provide healthcare professionals with a comprehensive assessment of donepezil 23 mg and its role in treating Alzheimer's disease (AD), the Donepezil 23 mg Expert Working Group (EWG) convened in June 2011 to critically evaluate the clinical trial database for this higher dose formulation and the members' clinical experience with its use. Discussions were based on a large, 6-month, phase 3 clinical trial in patients with moderate to severe AD that compared continuing donepezil 10 mg/day versus switching to 23 mg/day. In this trial, donepezil 23 mg/day demonstrated significantly greater cognitive benefits (mean change in Severe Impairment Battery score, 2.11 points; P < 0.001). Prespecified analyses showed that benefits were significant irrespective of concomitant memantine use. The EWG considered integrating these new data into clinical practice approaches. Dementia severity, tolerability of the 10 mg dose, and need for additional therapy were key selection criteria, as was monitoring of gastrointestinal side effects, as consideration of titration strategies is an important aspect of implementation. The EWG concluded that donepezil 23 mg is an efficacious therapy for moderate to severe AD, with or without concomitant memantine, extending the treatment opportunities available to manage moderate to severe AD dementia. EWG guidelines offer assistance to clinicians in choosing and implementing treatment options. © 2013 Blackwell Publishing Ltd.


Decourt B.,Sun Diagnostics | Walker A.,Sun Diagnostics | Gonzales A.,Sun Diagnostics | Malek-Ahmadi M.,Banner Sun Health Research Institute | And 6 more authors.
Platelets | Year: 2013

To date there is no validated peripheral biomarker to assist with the clinical diagnosis of Alzheimer's disease (AD). Platelet proteins have been studied as AD biomarkers with relative success. In this study, we investigated whether platelet BACE1 levels differ between AD and cognitively normal (CN) control patients. Using a newly developed ELISA method, we found that BACE1 levels were significantly lower in AD compared to CN subjects. These data were supported by the observation that several BACE1 isoforms, identified by Western blotting, were also lower in AD platelets. This proof-of-concept study provides evidence for testing platelet BACE1 levels as a peripheral AD biomarker using a novel, sensitive and inexpensive method. © 2013 Informa UK Ltd.


Decourt B.,Sun Diagnostics | Gonzales A.,Sun Diagnostics | Beach T.G.,Banner Sun Health Research Institute | Malek-Ahmadi M.,Banner Sun Health Research Institute | And 5 more authors.
Current Alzheimer Research | Year: 2013

The APOE genotype is a known susceptibility factor for Alzheimer's disease (AD). It is apparent that the presence of the APOE e{open}4 allele increases the risk for developing AD, lowers the age of onset in AD, and may influence the pathological burden seen in AD. In this study, we asked whether BACE1 levels differ by APOE genotype in the AD and non-demented (ND) brain. We isolated mid-frontal cortex (MFC) and mid-temporal cortex (MTC) from post-mortem ND and AD subjects that were APOE e{open}3/3, e{open}3/4, e{open}4/4 carriers. All AD subjects met NINDS-ADRDA and NIA-Reagan criteria for a diagnosis of AD. The MFC and MTC were homogenized and the lysates underwent ELISA and Western blotting for BACE1. The ELISA revealed that total BACE1 levels were lower in the MFC of AD compared to ND subjects. Furthermore, in APOE e{open}4 carriers BACE1 levels were lower than e{open}3/3 carriers in the ND frontal cortex. No difference in BACE1 levels was observed in AD MFC and in ND and AD MTC tissues. The ELISA results were confirmed by Western blotting. Our data suggest that brain BACEl levels may be influenced by the apolipoprotein E genotype before the onset of AD, providing an alternative explanation for the lower amyloid beta 42 levels in CSF in ND and AD subjects. © 2013 Bentham Science Publishers.


Sniderman A.D.,McGill University | Lamarche B.,Laval University | Contois J.H.,Sun Diagnostics | De Graaf J.,Radboud University Nijmegen
Current Opinion in Lipidology | Year: 2014

Purpose of review: Conventional methods, comparing the concentration of cholesterol to particle number as indices of cardiovascular risk, have not produced consistent results, in large part, because they treat these variables as independent and unrelated. However, although highly correlated, apolipoprotein B particles may contain a normal mass of cholesterol or may be cholesterol-depleted or cholesterol-enriched. Discordance analysis compares the predictive power of LDL-C and non-HDL-C to apolipoprotein B and LDL particle numbers in patients in whom they differ, that is, in whom they are discordant. The advantage of discordance analysis is that the results are not diluted by concordant data in which risk predictions cannot differ. Recent findings: The evidence, to date, consistently demonstrates that apolipoprotein B and LDL particle numbers are more accurate indices of cardiovascular risk than LDL-C or non-HDL-C. Summary: Discordance analysis is a methodological advance that allows the clinical value of closely correlated variables to be determined and demonstrates that cardiovascular risk is more closely related to the number of atherogenic particles than to the total mass of cholesterol within them. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Contois J.H.,Sun Diagnostics | Albert A.L.,Sun Diagnostics | Nguyen R.-A.,Sun Diagnostics
Clinica Chimica Acta | Year: 2014

Background: Immunoprecipitation (IP) of non-HDL particles with antisera provides the simplest and most specific method available for the separation of HDL. We compared the LipoSep™ IP reagent with the dextran sulfate/MgCl2 precipitation method (DS). Methods: The IP reagent (200. μl) was added to an equal volume of serum, vortexed, incubated for 10. min at room temperature, and microcentrifuged at 12,000. rpm for 10. min. Results: Equal volumes of a sample and the IP reagent precipitated apoB to 3.0. g/l without the coprecipitation of HDL. HDL-C measured in the supernatant after IP (Y) gave excellent agreement to DS precipitation (X) with a slope of 1.01, an intercept of 0.070. mmol/l (2.7. mg/dl), and a correlation of 0.99 (n. = 118; apoB 0.16-2.11. g/l). However, DS failed in most samples with moderate to elevated triglycerides. At triglyceride concentrations from 2.86 to 23.63. mmol/l (253-2091. mg/dl) the initial success rate was 65.4% for IP, while DS successfully precipitated only 5.8%. Success rate on repeat with additional reagent and/or sample dilution gave a success rate of 86.5% for IP and 40.4% for DS. Conclusion: The IP reagent and protocol is a simple, effective and highly specific tool for isolating HDL particles in human serum and is effective with high triglyceride samples. © 2014 Elsevier B.V.


Cole T.G.,Thom Cole Consulting LLC | Contois J.H.,Sun Diagnostics | Csako G.,U.S. National Institutes of Health | McConnell J.P.,Health Diagnostic Laboratory | And 6 more authors.
Clinical Chemistry | Year: 2013

BACKGROUND: The number of circulating LDL particles is a strong indicator of future cardiovascular disease (CVD) events, even superior to the concentration of LDL cholesterol. Atherogenic (primarily LDL) particle number is typically determined either directly by the serum concentration of apolipoprotein B (apo B) or indirectly by nuclear magnetic resonance (NMR) spectroscopy of serum to obtain NMR-derived LDL particle number (LDL-P). CONTENT: To assess the comparability of apo B and LDL-P, we reviewed 25 clinical studies containing 85 outcomes for which both biomarkers were determined. In 21 of 25 (84.0%) studies, both apo B and LDL-P were significant for at least 1 outcome. Neither was significant for any outcome in only 1 study (4.0%). In 50 of 85 comparisons (58.8%), both apo B and LDL-P had statistically significant associations with the clinical outcome, whereas in 17 comparisons (20.0%) neither was significantly associated with the outcome. In 18 comparisons (21.1%) there was discordance between apo B and LDL-P. CONCLUSIONS: In most studies, both apo B and LDL-P were comparable in association with clinical outcomes. The biomarkers were nearly equivalent in their ability to assess risk for CVD and both have consistently been shown to be stronger risk factors than LDL-C. We support the adoption of apo B and/or LDL-P as indicators of atherogenic particle numbers into CVD risk screening and treatment guidelines. Currently, in the opinion of this Working Group on Best Practices, apo B appears to be the preferable biomarker for guideline adoption because of its availability, scalability, standardization, and relatively low cost. © 2013 American Association for Clinical Chemistry.


Backes J.M.,University of Kansas | Dayspring T.D.,Foundation for Health Improvement and Technology | Hoefner D.M.,Health Diagnostic Laboratory | Contois J.H.,Sun Diagnostics | And 2 more authors.
Clinical Lipidology | Year: 2014

Isolated asymptomatic glycerol kinase deficiency (GKD) or 'pseudohypertriglyceridemia', is an X-linked recessive disorder resulting in hyperglyceroluria and hyperglycerolemia. Patients typically present with hypertriglyceridemia, which is unresponsive to therapy. The falsely elevated triglycerides are a result of clinical laboratories utilizing glycerol levels to report triglyceride concentrations. Glycerol blanking will account for the excess glycerol and provide accurate triglyceride measures. Pseudohypertriglyceridemia is linked to glucose impairment and other forms of GKD involving childhood metabolic crises and developmental limitations. Identifying patients with pseudohypertriglyceridemia prevents overestimation of cardiovascular risk and exposure to unnecessary lipid-altering agents; and heightens the awareness of the potential for symptomatic GKD in male offspring. We urge clinical labs to provide a glycerol-blanked triglyceride measurement for known or suspected pseudohypertriglyceridemia. © 2014 Future Medicine Ltd.


PubMed | Sun Diagnostics
Type: Journal Article | Journal: Current Alzheimer research | Year: 2013

The APOE genotype is a known susceptibility factor for Alzheimers disease (AD). It is apparent that the presence of the APOE 40 allele increases the risk for developing AD, lowers the age of onset in AD, and may influence the pathological burden seen in AD. In this study, we asked whether BACE1 levels differ by APOE genotype in the AD and non-demented (ND) brain. We isolated mid-frontal cortex (MFC) and mid-temporal cortex (MTC) from post-mortem ND and AD subjects that were APOE 3/3, 3/4, 4/4 carriers. All AD subjects met NINDS-ADRDA and NIA-Reagan criteria for a diagnosis of AD. The MFC and MTC were homogenized and the lysates underwent ELISA and Western blotting for BACE1. The ELISA revealed that total BACE1 levels were lower in the MFC of AD compared to ND subjects. Furthermore, in APOE 4 carriers BACE1 levels were lower than 3/3 carriers in the ND frontal cortex. No difference in BACE1 levels was observed in AD MFC and in ND and AD MTC tissues. The ELISA results were confirmed by Western blotting. Our data suggest that brain BACEl levels may be influenced by the apolipoprotein E genotype before the onset of AD, providing an alternative explanation for the lower amyloid beta 42 levels in CSF in ND and AD subjects.


PubMed | Sun Diagnostics
Type: | Journal: Clinica chimica acta; international journal of clinical chemistry | Year: 2014

Immunoprecipitation (IP) of non-HDL particles with antisera provides the simplest and most specific method available for the separation of HDL. We compared the LipoSep IP reagent with the dextran sulfate/MgCl2 precipitation method (DS).The IP reagent (200 l) was added to an equal volume of serum, vortexed, incubated for 10 min at room temperature, and microcentrifuged at 12,000 rpm for 10 min.Equal volumes of a sample and the IP reagent precipitated apoB to 3.0 g/l without the coprecipitation of HDL. HDL-C measured in the supernatant after IP (Y) gave excellent agreement to DS precipitation (X) with a slope of 1.01, an intercept of 0.070 mmol/l (2.7 mg/dl), and a correlation of 0.99 (n=118; apoB 0.16-2.11 g/l). However, DS failed in most samples with moderate to elevated triglycerides. At triglyceride concentrations from 2.86 to 23.63 mmol/l (253-2091 mg/dl) the initial success rate was 65.4% for IP, while DS successfully precipitated only 5.8%. Success rate on repeat with additional reagent and/or sample dilution gave a success rate of 86.5% for IP and 40.4% for DS.The IP reagent and protocol is a simple, effective and highly specific tool for isolating HDL particles in human serum and is effective with high triglyceride samples.

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