Alzheimer's disease (AD), the most common form of dementia, is characterized by the loss of normal functions of brain cells and neuronal death, ultimately leading to memory loss. Recent accumulating evidences have demonstrated the therapeutic potential of anti-diabetic agents, such as dipeptidyl peptidase-4 (DPP-4) inhibitors, for the treatment of Alzheimer's disease (AD), providing opportunities to explore and test the DPP-4 inhibitors for treating this fatal disease. Prior studies determining the efficacy of Pterocarpus marsupium (PM, Fabaceae) and Eugenia jambolana (EJ, Myrtaceae) extracts for ameliorating type 2 diabetes have demonstrated the DPP-4 inhibitory properties indicating the possibility of using of these extracts even for the treating AD. Therefore, in the present study, the neuroprotective roles of PM and EJ for ameliorating the streptozotocin (STZ) induced AD have been tested in rat model. Experimentally, PM and EJ extracts, at a dose range of 200 and 400mg/kg, were administered orally to STZ induced AD Wistar rats and cognitive evaluation tests were performed using radial arm maze and hole-board apparatus. Following 30 days of treatment with the extracts, a dose- and time-dependent attenuation of AD pathology, as evidenced by decreasing amyloid beta 42, total tau, phosphorylated tau and neuro-inflammation with an increase in glucagon-like peptide-1 (GLP-1) levels was observed. Therefore, PM and EJ extracts contain cognitive enhancers as well as neuroprotective agents against STZ induced AD.

Dipeptidyl peptidase 4 inhibition by Pterocarpus marsupium and Eugenia jambolana ameliorates streptozotocin induced Alzheimer s disease

Viruses are responsible for multiple infections in humans that impose huge health burdens on individuals and populations worldwide. Therefore, numerous diagnostic methods and strategies have been developed for prevention, management, and decreasing the burden of viral diseases, each having its advantages and limitations. Viral infections are commonly detected using serological and nucleic acid-based methods. However, these conventional and clinical approaches have some limitations that can be resolved by implementing other detector devices. Therefore, the search for sensitive, selective, portable, and costless approaches as efficient alternative clinical methods for point of care testing (POCT) analysis has gained much attention in recent years. POCT is one of the ultimate goals in virus detection, and thus, the tests need to be rapid, specific, sensitive, accessible, and user-friendly. In this review, after a brief overview of viruses and their characteristics, the conventional viral detection methods, the clinical approaches, and their advantages and shortcomings are firstly explained. Then, LFA systems working principles, benefits, classification are discussed. Furthermore, the studies regarding designing and employing LFAs in diagnosing different types of viruses, especially SARS-CoV-2 as a main concern worldwide and innovations in the LFAs' approaches and designs, are comprehensively discussed here. Furthermore, several strategies addressed in some studies for overcoming LFA limitations like low sensitivity are reviewed. Numerous techniques are adopted to increase sensitivity and perform quantitative detection. Employing several visualization methods, using different labeling reporters, integrating LFAs with other detection methods to benefit from both LFA and the integrated detection device advantages, and designing unique membranes to increase reagent reactivity, are some of the approaches that are highlighted.

Lateral flow assays (LFA) as an alternative medical diagnosis method for detection of virus species: The intertwine of nanotechnology with sensing strategies.

Background The diagnostic challenges associated with the COVID‐19 pandemic resulted in rapid development of diagnostic test methods for detecting SARS‐CoV‐2 infection. Serology tests to detect the presence of antibodies to SARS‐CoV‐2 enable detection of past infection and may detect cases of SARS‐CoV‐2 infection that were missed by earlier diagnostic tests. Understanding the diagnostic accuracy of serology tests for SARS‐CoV‐2 infection may enable development of effective diagnostic and management pathways, inform public health management decisions and understanding of SARS‐CoV‐2 epidemiology. Objectives To assess the accuracy of antibody tests, firstly, to determine if a person presenting in the community, or in primary or secondary care has current SARS‐CoV‐2 infection according to time after onset of infection and, secondly, to determine if a person has previously been infected with SARS‐CoV‐2. Sources of heterogeneity investigated included: timing of test, test method, SARS‐CoV‐2 antigen used, test brand, and reference standard for non‐SARS‐CoV‐2 cases. Search methods The COVID‐19 Open Access Project living evidence database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) was searched on 30 September 2020. We included additional publications from the Evidence for Policy and Practice Information and Co‐ordinating Centre (EPPI‐Centre) ‘COVID‐19: Living map of the evidence’ and the Norwegian Institute of Public Health ’NIPH systematic and living map on COVID‐19 evidence’. We did not apply language restrictions. Selection criteria We included test accuracy studies of any design that evaluated commercially produced serology tests, targeting IgG, IgM, IgA alone, or in combination. Studies must have provided data for sensitivity, that could be allocated to a predefined time period after onset of symptoms, or after a positive RT‐PCR test. Small studies with fewer than 25 SARS‐CoV‐2 infection cases were excluded. We included any reference standard to define the presence or absence of SARS‐CoV‐2 (including reverse transcription polymerase chain reaction tests (RT‐PCR), clinical diagnostic criteria, and pre‐pandemic samples). Data collection and analysis We use standard screening procedures with three reviewers. Quality assessment (using the QUADAS‐2 tool) and numeric study results were extracted independently by two people. Other study characteristics were extracted by one reviewer and checked by a second. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test and, for meta‐analysis, we fitted univariate random‐effects logistic regression models for sensitivity by eligible time period and for specificity by reference standard group. Heterogeneity was investigated by including indicator variables in the random‐effects logistic regression models. We tabulated results by test manufacturer and summarised results for tests that were evaluated in 200 or more samples and that met a modification of UK Medicines and Healthcare products Regulatory Agency (MHRA) target performance criteria. Main results We included 178 separate studies (described in 177 study reports, with 45 as pre‐prints) providing 527 test evaluations. The studies included 64,688 samples including 25,724 from people with confirmed SARS‐CoV‐2; most compared the accuracy of two or more assays (102/178, 57%). Participants with confirmed SARS‐CoV‐2 infection were most commonly hospital inpatients (78/178, 44%), and pre‐pandemic samples were used by 45% (81/178) to estimate specificity. Over two‐thirds of studies recruited participants based on known SARS‐CoV‐2 infection status (123/178, 69%). All studies were conducted prior to the introduction of SARS‐CoV‐2 vaccines and present data for naturally acquired antibody responses. Seventy‐nine percent (141/178) of studies reported sensitivity by week after symptom onset and 66% (117/178) for convalescent phase infection. Studies evaluated enzyme‐linked immunosorbent assays (ELISA) (165/527; 31%), chemiluminescent assays (CLIA) (167/527; 32%) or lateral flow assays (LFA) (188/527; 36%). Risk of bias was high because of participant selection (172, 97%); application and interpretation of the index test (35, 20%); weaknesses in the reference standard (38, 21%); and issues related to participant flow and timing (148, 82%). We judged that there were high concerns about the applicability of the evidence related to participants in 170 (96%) studies, and about the applicability of the reference standard in 162 (91%) studies. Average sensitivities for current SARS‐CoV‐2 infection increased by week after onset for all target antibodies. Average sensitivity for the combination of either IgG or IgM was 41.1% in week one (95% CI 38.1 to 44.2; 103 evaluations; 3881 samples, 1593 cases), 74.9% in week two (95% CI 72.4 to 77.3; 96 evaluations, 3948 samples, 2904 cases) and 88.0% by week three after onset of symptoms (95% CI 86.3 to 89.5; 103 evaluations, 2929 samples, 2571 cases). Average sensitivity during the convalescent phase of infection (up to a maximum of 100 days since onset of symptoms, where reported) was 89.8% for IgG (95% CI 88.5 to 90.9; 253 evaluations, 16,846 samples, 14,183 cases), 92.9% for IgG or IgM combined (95% CI 91.0 to 94.4; 108 evaluations, 3571 samples, 3206 cases) and 94.3% for total antibodies (95% CI 92.8 to 95.5; 58 evaluations, 7063 samples, 6652 cases). Average sensitivities for IgM alone followed a similar pattern but were of a lower test accuracy in every time slot. Average specificities were consistently high and precise, particularly for pre‐pandemic samples which provide the least biased estimates of specificity (ranging from 98.6% for IgM to 99.8% for total antibodies). Subgroup analyses suggested small differences in sensitivity and specificity by test technology however heterogeneity in study results, timing of sample collection, and smaller sample numbers in some groups made comparisons difficult. For IgG, CLIAs were the most sensitive (convalescent‐phase infection) and specific (pre‐pandemic samples) compared to both ELISAs and LFAs (P < 0.001 for differences across test methods). The antigen(s) used (whether from the Spike‐protein or nucleocapsid) appeared to have some effect on average sensitivity in the first weeks after onset but there was no clear evidence of an effect during convalescent‐phase infection. Investigations of test performance by brand showed considerable variation in sensitivity between tests, and in results between studies evaluating the same test. For tests that were evaluated in 200 or more samples, the lower bound of the 95% CI for sensitivity was 90% or more for only a small number of tests (IgG, n = 5; IgG or IgM, n = 1; total antibodies, n = 4). More test brands met the MHRA minimum criteria for specificity of 98% or above (IgG, n = 16; IgG or IgM, n = 5; total antibodies, n = 7). Seven assays met the specified criteria for both sensitivity and specificity. In a low‐prevalence (2%) setting, where antibody testing is used to diagnose COVID‐19 in people with symptoms but who have had a negative PCR test, we would anticipate that 1 (1 to 2) case would be missed and 8 (5 to 15) would be falsely positive in 1000 people undergoing IgG or IgM testing in week three after onset of SARS‐CoV‐2 infection. In a seroprevalence survey, where prevalence of prior infection is 50%, we would anticipate that 51 (46 to 58) cases would be missed and 6 (5 to 7) would be falsely positive in 1000 people having IgG tests during the convalescent phase (21 to 100 days post‐symptom onset or post‐positive PCR) of SARS‐CoV‐2 infection. Authors' conclusions Some antibody tests could be a useful diagnostic tool for those in whom molecular‐ or antigen‐based tests have failed to detect the SARS‐CoV‐2 virus, including in those with ongoing symptoms of acute infection (from week three onwards) or those presenting with post‐acute sequelae of COVID‐19. However, antibody tests have an increasing likelihood of detecting an immune response to infection as time since onset of infection progresses and have demonstrated adequate performance for detection of prior infection for sero‐epidemiological purposes. The applicability of results for detection of vaccination‐induced antibodies is uncertain. 

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Antibody tests for identification of current and past infection with SARS-CoV-2

Tau cleavage plays a crucial role in the onset and progression of Alzheimer's Disease (AD), a widespread neurodegenerative disease whose incidence is expected to increase in the next years. While genetic and familial forms of AD (fAD) occurring early in life represent less than 1%, the sporadic and late-onset ones (sAD) are the most common, with ageing being an important risk factor. Intracerebroventricular (ICV) infusion of streptozotocin (STZ)-a compound used in the systemic induction of diabetes due to its ability to damage the pancreatic β cells and to induce insulin resistance-mimics in rodents several behavioral, molecular and histopathological hallmarks of sAD, including memory/learning disturbance, amyloid-β (Aβ) accumulation, tau hyperphosphorylation, oxidative stress and brain glucose hypometabolism. We have demonstrated that pathological truncation of tau at its N-terminal domain occurs into hippocampi from two well-established transgenic lines of fAD animal models, such as Tg2576 and 3xTg mice, and that it's in vivo neutralization via intravenous (i.v.) administration of the cleavage-specific anti-tau 12A12 monoclonal antibody (mAb) is strongly neuroprotective. Here, we report the therapeutic efficacy of 12A12mAb in STZ-infused mice after 14 days (short-term immunization, STIR) and 21 days (long-term immunization regimen, LTIR) of i.v. delivery. A virtually complete recovery was detected after three weeks of 12A12mAb immunization in both novel object recognition test (NORT) and object place recognition task (OPRT). Consistently, three weeks of this immunization regimen relieved in hippocampi from ICV-STZ mice the AD-like up-regulation of amyloid precursor protein (APP), the tau hyperphosphorylation and neuroinflammation, likely due to modulation of the PI3K/AKT/GSK3-β axis and the AMP-activated protein kinase (AMPK) activities. Cerebral oxidative stress, mitochondrial impairment, synaptic and histological alterations occurring in STZ-infused mice were also strongly attenuated by 12A12mAb delivery. These results further strengthen the causal role of N-terminal tau cleavage in AD pathogenesis and indicate that its specific neutralization by non-invasive administration of 12A12mAb can be a therapeutic option for both fAD and sAD patients, as well as for those showing type 2 diabetes as a comorbidity.

Tau Cleavage Contributes to Cognitive Dysfunction in Strepto-Zotocin-Induced Sporadic Alzheimer's Disease (sAD) Mouse Model.

Alzheimer’s disease (AD) is a significant health concern with enormous social and economic impact globally. The gradual deterioration of cognitive functions and irreversible neuronal losses are primary features of the disease. Even after decades of research, most therapeutic options are merely symptomatic, and drugs in clinical practice present numerous side effects. Lack of effective diagnostic techniques prevents the early prognosis of disease, resulting in a gradual deterioration in the quality of life. Furthermore, the mechanism of cognitive impairment and AD pathophysiology is poorly understood. Microfluidics exploits different microscale properties of fluids to mimic environments on microfluidic chip-like devices. These miniature multichambered devices can be used to grow cells and 3D tissues in vitro, analyze cell-to-cell communication, decipher the roles of neural cells such as microglia, and gain insights into AD pathophysiology. This review focuses on the applications and impact of microfluidics on AD research. We discuss the technical challenges and possible solutions provided by this new cutting-edge technique to understand disease-associated pathways and mechanisms.

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Microfluidic Platforms to Unravel Mysteries of Alzheimer's Disease: How Far Have We Come?

Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, which has reached 28 million cases worldwide in 1 year. The serological detection of antibodies against the virus will play a pivotal role in complementing molecular tests to improve diagnostic accuracy, contact tracing, vaccine efficacy testing, and seroprevalence surveillance. Here, we aimed first to evaluate a lateral flow assay's ability to identify specific IgM and IgG antibodies against SARS-CoV-2 and second, to report the seroprevalence estimates of these antibodies among health care workers and healthy volunteer blood donors in Panama. We recruited study participants between April 30th and July 7th, 2020. For the test validation and performance evaluation, we analyzed serum samples from participants with clinical symptoms and confirmed positive RT-PCR for SARS-CoV-2, and a set of pre-pandemic serum samples. We used two by two table analysis to determine the test positive and negative percentage agreement as well as the Kappa agreement value with a 95% confidence interval. Then, we used the lateral flow assay to determine seroprevalence among serum samples from COVID-19 patients, potentially exposed health care workers, and healthy volunteer donors. Our results show this assay reached a positive percent agreement of 97.2% (95% CI 84.2-100.0%) for detecting both IgM and IgG. The assay showed a Kappa of 0.898 (95%CI 0.811-0.985) and 0.918 (95% CI 0.839-0.997) for IgM and IgG, respectively. The evaluation of serum samples from hospitalized COVID-19 patients indicates a correlation between test sensitivity and the number of days since symptom onset; the highest positive percent agreement [87% (95% CI 67.0-96.3%)] was observed at ≥15 days post-symptom onset (PSO). We found an overall antibody seroprevalence of 11.6% (95% CI 8.5-15.8%) among both health care workers and healthy blood donors. Our findings suggest this lateral flow assay could contribute significantly to implementing seroprevalence testing in locations with active community transmission of SARS-CoV-2.

Performance of a Point of Care Test for Detecting IgM and IgG Antibodies Against SARS-CoV-2 and Seroprevalence in Blood Donors and Health Care Workers in Panama

Alzheimer's disease (AD) is a growing neurodegenerative disease without effective treatments or therapies. Despite the use of different approaches and an extensive variety of genetic amyloid based models, therapeutic strategies remain elusive. AD is characterized by three main pathological hallmarks that include amyloid-β plaques, neurofibrillary tangles, and neuroinflammatory processes; however, many other pathological mechanisms have been described in the literature. Nonetheless, the study of the disease and the screening of potential therapies is heavily weighted toward the study of amyloid-β transgenic models. Non-transgenic models may aid in the study of complex pathological states and provide a suitable complementary alternative to evaluating therapeutic biomedical and intervention strategies. In this review, we evaluate the literature on non-transgenic alternatives, focusing on the use of these models for testing therapeutic strategies, and assess their contribution to understanding AD. This review aims to underscore the need for a shift in preclinical research on intervention strategies for AD from amyloid-based to alternative, complementary non-amyloid approaches.

Critical Review of the Alzheimer's Disease Non-Transgenic Models: Can They Contribute to Disease Treatment?

Apolipoprotein ɛ4 allele (APOEɛ4) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD), but inconsistencies have arisen in studies with Hispanics. The objective of this study was to explore APOEɛ4 expression and cognitive function in a sample of Panamanian older adults, including healthy controls, mild cognitive impairment, and AD. Participants with at least one copy of APOEɛ4 had a significantly lower performance in global cognition, verbal memory, executive functions, visuospatial abilities, regardless of diagnosis. The present study contributes to the understanding of the association of APOEɛ4 and impairment in specific cognitive domains in elderly Hispanics.

Julio A Flores-Cuadra

Papers

Performance of a Point of Care Test for Detecting IgM and IgG Antibodies Against SARS-CoV-2 and Seroprevalence in Blood Donors and Health Care Workers in Panama

Critical Review of the Alzheimer's Disease Non-Transgenic Models: Can They Contribute to Disease Treatment?

Apolipoprotein ɛ4 Affects Multiple Domains of Neuropsychological Functioning in a Sample of Elderly Hispanics.