Clinical Correlates of the PET-based Braak Staging Framework in Alzheimer's Disease.

In vivo Alzheimer's disease diagnosis and staging is traditionally based on clinical features. However, the agreement between clinical and pathological Alzheimer's disease diagnosis, whose diagnosis assessment includes amyloid and Braak histopathological tau staging, is not completely convergent. The development of positron emission tomography (PET) tracers targeting neurofibrillary tangles offers prospects for advancing the staging of Alzheimer's disease from both biological and clinical perspectives. Recent advances in radiochemistry made it possible to apply the postmortem Braak staging framework to tau-PET images obtained in vivo. Here, our aim is to provide a narrative review of the current literature on the relationship between Alzheimer's disease clinical features and the PET-based Braak staging framework. Overall, the available studies support the stepwise increase in disease severity following the advance of PET-based Braak stages, with later stages being associated with worse cognitive and clinical symptoms. In line with this, there is a trend for unimpaired cognition, mild cognitive impairment, and Alzheimer's disease dementia to be compatible with early, intermediate, and late patterns of tau deposition based on PET-based Braak stages. Moreover, neuropsychiatric symptom severity seems to be linked to the extent of tau-PET signal across Braak areas. In sum, this framework seems to correspond well with the clinical progression of Alzheimer's disease, which is an indication of its potential utility in research and clinical practice, especially for detecting preclinical tau levels in individuals without symptoms. However, further research is needed to improve the generalizability of these findings and to better understand the applications of this staging framework.

Adding the Topographical Information from Tau-PET to the A/T/(N) Framework: Steps Towards Staging AD in Vivo.

Biomarkers have revolutionized the study and clinical diagnosis of Alzheimer's disease (AD). While amyloid-ß accumulation begins decades before the onset of clinical dementia in AD, tau pathology is more closely associated in both space and time to neurodegeneration and to clinical dysfunction. Correspondingly, tau-PET may prove useful in determining the severity of AD. Building on the biological research framework for AD, we review here methods and rationale to stage the severity of AD in vivo using the topographical distribution of tau-PET. We discuss how tau-PET can be used to detect early and subthreshold tau accumulation in medial temporal cortices prior to the onset of cognitive symptoms. Furthermore, tau-PET can be used to monitor the severity of AD as tau-PET spreads to association cortices and finally primary sensory cortices. We discuss the utility of tau-PET to monitor the progression of AD, the flexibility of potential approaches, and applications for clinical trials. In this regard, topographical information from tau-PET is a useful addition to the A/T/(N) framework.

Neuroinflammation Biomarkers in the AT(N) Framework Across the Alzheimer's Disease Continuum.

In the past years, neuroinflammation has been widely investigated in Alzheimer's disease (AD). Evidence from animal, in vivo and post-mortem studies has shown that inflammatory changes are a common feature of the disease, apparently happening in response to amyloid-beta and tau accumulation. Progress in imaging and fluid biomarkers now allows for identifying surrogate markers of neuroinflammation in living individuals, which may offer unprecedented opportunities to better understand AD pathogenesis and progression. In this context, inflammatory mediators and glial proteins (mainly derived from microglial cells and astrocytes) seem to be the most promising biomarkers. Here, we discuss the biological basis of neuroinflammation in AD, revise the proposed neuroinflammation biomarkers, describe what we have learned from anti-inflammatory drug trials, and critically discuss the potential addition of these biomarkers in the AT(N) framework.

Assessment of salinity-related mortality of freshwater bacteria in the saint lawrence estuary.

The growth response of freshwater bacteria from the St. Lawrence River, exposed to brackish waters (salinity of 0 to 20(permil)) from the upper estuary, was assessed by a methodology requiring the combined use of dilution cultures and diffusion chambers. The longitudinal distribution of bacterial abundance in waters within this salinity range was also examined. Growth of the freshwater bacteria was reduced by 15 and 50% after exposure to salinities of 10 and 20(permil), respectively. At lower salinities, no growth reduction was observed, and at a salinity of 2(permil), growth was even stimulated. Longitudinal distribution data showed that bacterial abundance also peaked at this salinity. In contrast with an earlier hypothesis, this study shows that the decline of bacterial abundance in the low-salinity waters of the estuary is not caused by salinity-related mortality of freshwater bacteria, because the mixing time between fresh and marine (>20(permil)) waters is relatively long (days). However, results suggest that mortality of freshwater bacteria can be an important process in estuaries with shorter mixing times (hours). The combined use of diffusion chambers and dilution cultures proved to be a valuable methodology for assessing growth (or mortality) of bacteria exposed to environmental gradients.

Direct coupling of marine invertebrate spawning with phytoplankton blooms.

Spawning of green sea urchins and blue mussels may be triggered by a heat-stable metabolite released by various species of phytoplankton. Mussels require a higher phytoplankton density for a maximum response than urchins, perhaps because mussels are exposed to higher concentrations of phytoplankton as a result of their filtering activity. Phytoplankton as a spawning cue appears to integrate numerous physical and biotic factors indicating favorable conditions for larval growth and survival. Evolution of similar direct coupling of the larval phase with phytoplankton blooms may be common among marine invertebrates.