Retinal vascular biomarkers for early detection and monitoring of Alzheimer's disease

The earliest detectable change in Alzheimer''s disease (AD) is the buildup of amyloid plaque in the brain. Early detection of AD, prior to irreversible neurological damage, is important for the efficacy of current interventions as well as for the development of new treatments. Although PiB-PET imaging and CSF amyloid are the gold standards for early AD diagnosis, there are practical limitations for population screening. AD-related pathology occurs primarily in the brain, but some of the hallmarks of the disease have also been shown to occur in other tissues, including the retina, which is more accessible for imaging. Retinal vascular changes and degeneration have previously been reported in AD using optical coherence tomography and laser Doppler techniques. This report presents results from analysis of retinal photographs from AD and healthy control participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing. This is the first study to investigate retinal blood vessel changes with respect to amyloid plaque burden in the brain. We demonstrate relationships between retinal vascular parameters, neocortical brain amyloid plaque burden and AD. A number of RVPs were found to be different in AD. Two of these RVPs, venular branching asymmetry factor and arteriolar length-to-diameter ratio, were also higher in healthy individuals with high plaque burden (P=0.01 and P=0.02 respectively, after false discovery rate adjustment). Retinal photographic analysis shows potential as an adjunct for early detection of AD or monitoring of AD-progression or response to treatments.     

Use of the DISST Model to Estimate the HOMA and Matsuda Indexes Using Only a Basal Insulin Assay

Background:It is hypothesized that early detection of reduced insulin sensitivity (SI) could prompt intervention that may reduce the considerable financial strain type 2 diabetes mellitus (T2DM) places on global health care. Reduction of the cost of already inexpensive SI metrics such as the Matsuda and HOMA indexes would enable more widespread, economically feasible use of these metrics for screening. The goal of this research was to determine a means of reducing the number of insulin samples and therefore the cost required to provide an accurate Matsuda Index value.Method:The Dynamic Insulin Sensitivity and Secretion Test (DISST) model was used with the glucose and basal insulin measurements from an Oral Glucose Tolerance Test (OGTT) to predict patient insulin responses. The insulin response to the OGTT was determined via population based regression analysis that incorporated the 60-minute glucose and basal insulin values.Results:The proposed method derived accurate and precise Matsuda Indices as compared to the fully sampled Matsuda (R = .95) using only the basal assay insulin-level data and 4 glucose measurements. Using a model employing the basal insulin also allows for determination of the 1-day HOMA value.Conclusion:The DISST model was successfully modified to allow for the accurate prediction an individual’s insulin response to the OGTT. In turn, this enabled highly accurate and precise estimation of a Matsuda Index using only the glucose and basal insulin assays. As insulin assays account for the majority of the cost of the Matsuda Index, this model offers a significant reduction in assay cost.     

Arterial internal elastic lamina holes: relationship to function?

Internal elastic lamina (IEL) hole (fenestration) characteristics and myoendothelial gap junction (MEGJ) density were examined in selected resistance and conduit arteries of normal and diseased rat and mouse models, using conventional, ultrastructural and confocal microscopy methods. Selected vessels were those commonly used in functional studies: thoracic aorta, proximal and distal mesenteric, caudal, saphenous, middle‐cerebral and caudal cerebellar artery. Rat and mouse strains and treatment groups examined were Dahl, Sprague Dawley, Wistar Kyoto, Wistar, spontaneously hypertensive (SHR), deoxycorticosterone (DOC) treated rat; and apolipoprotein E knockout, C57/BL6 and BALB/c mice. Vessel size (as IEL circumference), IEL hole and MEGJ density were quantified. In mesenteric arteries, the width of IEL holes and the percent of IEL occupied by holes were also determined. IEL hole density varied significantly within and between mesenteric artery beds, even among normotensive rat strains. Among the hypertensive rats (SHR and DOC), hole density in some vessels was higher in the normotensives than in the hypertensives within each strain, whereas in Dahl rats, hole density was similar between hypertensives and normotensives. Hole density was not correlated with the formation of intimal lesions in superior mesenteric artery. There was no positive general correlation between IEL hole and MEGJ density in resistance and conduit vessels. However, there was a positive correlation between the size of some resistance arteries and MEGJ density, although such a relationship did not hold for conduit vessels or during development, and there was no such relationship between vessel size and IEL hole density. Whilst IEL holes are obviously required for MEGJ communication, their presence is not an indication of contact‐mediated communication, but rather may be related to the presence of sites for the low resistance passage of diffusion‐mediated release of vasoactive endothelial and smooth muscle substances.