Leslie M. Shaw

Personal ViewTracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers

In 2010, we put forward a hypothetical model of the major biomarkers of Alzheimers disease (AD). The model was received with interest because we described the temporal evolution of AD biomarkers in relation to each other and to the onset and progression of clinical symptoms. Since then, evidence has accumulated that supports the major assumptions of this model. Evidence has also appeared that challenges some of our assumptions, which has allowed us to modify our original model. Refinements to our model include indexing of individuals by time rather than clinical symptom severity; incorporation of interindividual variability in cognitive impairment associated with progression of AD pathophysiology; modifications of the specific temporal ordering of some biomarkers; and recognition that the two major proteinopathies underlying AD biomarker changes, amyloid β (Aβ) and tau, might be initiated independently in sporadic AD, in which we hypothesise that an incident Aβ pathophysiology can accelerate antecedent limbic and brainstem tauopathy.

Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer's disease research

The lack of readily available biomarkers is a significant hindrance toward progressing to effective therapeutic and preventative strategies for Alzheimers disease (AD). Blood‐based biomarkers have potential to overcome access and cost barriers and greatly facilitate advanced neuroimaging and cerebrospinal fluid biomarker approaches. Despite the fact that preanalytical processing is the largest source of variability in laboratory testing, there are no currently available standardized preanalytical guidelines. The current international working group provides the initial starting point for such guidelines for standardized operating procedures (SOPs). It is anticipated that these guidelines will be updated as additional research findings become available. The statement provides (1) a synopsis of selected preanalytical methods utilized in many international AD cohort studies, (2) initial draft guidelines/SOPs for preanalytical methods, and (3) a list of required methodological information and protocols to be made available for publications in the field to foster cross‐validation across cohorts and laboratories.

The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement

The overall goal of the Alzheimers Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimers disease (AD) clinical trials. ADNI‐3, which began on August 1, 2016, is a 5‐year renewal of the current ADNI‐2 study.

Anxiety is related to Alzheimer's disease markers in cerebrospinal fluid of subjects with mild cognitive impairment

in both anterior temporal lobes while FDG PET scan showed posterior hypofixation atypical for AD. The CSF of tau-protein (600 pg/ml), phosphorylated tau (87 pg/ml) were increased, whereas the concentration of beta-amyloid protein (Abeta1-42) was decreased (480 pg/ml) according to our cut-off (Dumurgier et al.) suggesting AD CSF profile. Conclusions: Among different clinical AD phenotype, FTD clinical presentation must not be misdiagnosed. CSF biomarkers are helpful to diagnose these patients, establish an accurate diagnosis and introduce a specific treatment.