Head-to-head comparison of amplified plasmonic exosome Aβ42 platform and single-molecule array immunoassay in a memory clinic cohort

Background: Various blood biomarkers reflecting brain amyloid‐β (Aβ) load have recently been proposed with promising results. However, to date, no comparative study among blood biomarkers has been reported. Our objective is to examine the diagnostic performance and cost effectiveness of three blood biomarkers on the same cohort. Methods: Using the same cohort (n=68), we compared the performance of the single‐molecule array (Simoa)‐Aβ40 and Aβ42, Aβ42/Aβ40 and the amplified plasmonic exosome (APEX)‐Aβ42 blood biomarkers using amyloid PET as the reference standard. We also determined the extent to which these blood tests can reduce the recruitment cost of clinical trials by identifying Amyloid positive (Aβ+) participants. Results: Compared to Simoa biomarkers, APEX‐Aβ42 showed significantly higher correlations with amyloid PET retention values and excellent diagnostic performance (sensitivity=100%, specificity=93.3%, AUC=0.995). When utilized for clinical trial recruitment, our simulation showed that pre‐screening with blood biomarkers followed by a confirmatory amyloid PET imaging would roughly half the cost (56.8% reduction for APEX‐Aβ42 and 48.6% for Simoa‐Aβ42/Aβ40) as compared to the situation where only PET imaging is used. Moreover, with a 100% sensitivity; APEX‐Aβ42 pre‐screening does not increase the required number of initial participants. Conclusions: With its high diagnostic performance, APEX is an ideal candidate for Aβ+ subject identification, monitoring, primary care screening, and could efficiently enrich clinical trials with Aβ+ participants while halving recruitment costs

New Clathrin-Based Nanoplatforms for Magnetic Resonance Imaging

Background: Magnetic Resonance Imaging (MRI) has high spatial resolution, but low sensitivity for visualization of molecular targets in the central nervous system (CNS). Our goal was to develop a new MRI method with the potential for non-invasive molecular brain imaging. We herein introduce new bio-nanotechnology approaches for designing CNS contrast media based on the ubiquitous clathrin cell protein. Methodology/Principal Findings: The first approach utilizes three-legged clathrin triskelia modified to carry 81 gadolinium chelates. The second approach uses clathrin cages self-assembled from triskelia and designed to carry 432 gadolinium chelates. Clathrin triskelia and cages were characterized by size, structure, protein concentration, and chelate and gadolinium contents. Relaxivity was evaluated at 0.47 T. A series of studies were conducted to ascertain whether fluorescent-tagged clathrin nanoplatforms could cross the blood brain barriers (BBB) unaided following intranasal, intravenous, and intraperitoneal routes of administration. Clathrin nanoparticles can be constituted as triskelia (18.5 nm in size), and as cages assembled from them (55 nm). The mean chelate: clathrin heavy chain molar ratio was 27.0464.8: 1 fo

Magnetic resonance imaging (MRI) contrast agents for tumor diagnosis

10.1260/2040-2295.4.1.23Journal of Healthcare Engineering4123-4

Controlled preparation of a heterometallic lanthanide complex containing different lanthanides in symmetrical binding pockets.

A heterometallic lanthanide complex has been prepared by sequential deprotection and complexation of an orthogonally protected ligand: luminescence and NMR spectroscopy have been used to probe the integrity of the complex

Harnessing CURATE.AI for N-of-1 Optimization Analysis of Combination Therapy in Hypertension Patients: A Retrospective Case Series

10.1002/adtp.202100091Advanced Therapeutics4102100091-210009

The Association between Standard Electrocardiography and Cerebral Small Vessel Disease in a Memory Clinic Study

Background: P-wave terminal force in lead V1 (PTFV1) on electrocardiography has been associated with atrial fibrillation and ischemic stroke. Objective: To investigate whether PTFV1 is associated with cerebral small vessel disease (CSVD) markers and etiological subtypes of cognitive impairment and dementia. Methods: Participants were recruited from ongoing memory clinic study between August 2010 to January 2019. All participants underwent physical and medical evaluation along with an electrocardiography and 3 T brain magnetic resonance imaging. Participants were classified as no cognitive impairment, cognitive impairment no dementia, vascular cognitive impairment no dementia, and dementia subtypes (Alzheimer's disease and vascular dementia). Elevated PTFV1 was defined as > 4,000μV×ms and measured manually on ECG. Results: Of 408 participants, 78 (19.1%) had elevated PTFV1 (37 women [47%]; mean [SD] age, 73.8 [7.2] years). The participants with elevated PTFV1 had higher burden of lacunes, cerebral microbleeds (CMB), and cortical microinfarcts. As for the CMB location, persons with strictly deep CMB and mixed CMB had significantly higher PTFV1 than those with no CMB (p = 0.005, p = 0.007). Regardless of adjustment for cardiovascular risk factors and/or heart diseases, elevated PTFV1 was significantly associated with presence of CMB (odds ratio, 2.26; 95% CI,1.33-3.91). Conclusion: Elevated PTFV1 was associated with CSVD, especially deep CMB. PTFV1 in vascular dementia was also higher compared to Alzheimer's disease. Thus, PTFV1 might be a potential surrogate marker of brain-heart connection and vascular brain damage

Brain amyloid ?, cerebral small vessel disease, and cognition: A memory clinic study

OBJECTIVE: To evaluate the association between brain amyloid β (Aβ) and cerebral small vessel disease (CSVD) markers, as well as their joint effect on cognition, in a memory clinic study. METHODS: A total of 186 individuals visiting a memory clinic, diagnosed with no cognitive impairment, cognitive impairment no dementia (CIND), Alzheimer dementia (AD), or vascular dementia were included. Brain Aβ was measured by [11C] Pittsburgh compound B-PET global standardized uptake value ratio (SUVR). CSVD markers including white matter hyperintensities (WMH), lacunes, and cerebral microbleeds (CMBs) were graded on MRI. Cognition was assessed by neuropsychological testing. RESULTS: An increase in global SUVR is associated with a decrease in Mini-Mental State Examination (MMSE) in CIND and AD, as well as a decrease in global cognition Z score in AD, independent of age, education, hippocampal volume, and markers of CSVD. A significant interaction between global SUVR and WMH was found in relation to MMSE in CIND (P for interaction: 0.009), with an increase of the effect size of Aβ (β = -6.57 [-9.62 to -3.54], p < 0.001) compared to the model without the interaction term (β = -2.91 [-4.54 to -1.29], p = 0.001). CONCLUSION: Higher global SUVR was associated with worse cognition in CIND and AD, but was augmented by an interaction between global SUVR and WMH only in CIND. This suggests that Aβ and CSVD are independent processes with a possible synergistic effect between Aβ and WMH in individuals with CIND. There was no interaction effect between Aβ and lacunes or CMBs. Therefore, in preclinical phases of AD, WMH should be targeted as a potentially modifiable factor to prevent worsening of cognitive dysfunction