Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers

Abstract

Biomarkers sensitive to functional impairment, neuronal loss, tau, and amyloid pathology based on MR, PET, and CSF studies are increasingly used to diagnose Alzheimer's disease (AD), but clinical validation is incomplete, hampering reimbursement by payers, widespread clinical implementation, and impacting on health care quality. An expert group convened to develop a strategic research agenda to foster the clinical validation of AD biomarkers. These demonstrated sufficient evidence of analytical validity (phase I of a structured framework adapted from oncology). Research priorities were identified based on incomplete clinical validity (phases II and III), and clinical utility (phases IV and V). Priorities included: definition of the assays; reading procedures and thresholds for normality; performance in detecting early disease; accounting for the effect of covariates; diagnostic algorithms comprising combinations of biomarkers; and developing best practice guidelines for the use of biomarkers in qualified memory clinics in the context of phase IV studies. 5 GlossaryBiomarker. An objective measure of a biological or pathogenic process with the purpose of evaluating disease risk or prognosis, guiding clinical diagnosis or monitoring therapeutic interventions. While the term originally referred to traceable substances produced by or introduced into an organism, it later evolved to any measurable parameter, including those obtained via imaging procedures.Roadmap. Objective-oriented, structured, and efficient action plan. In science and technology also called "strategic research agenda".Alzheimer's disease (AD) dementia. Traditionally and according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria, Alzheimer's disease was defined as a syndrome with progressive cognitive impairment severe enough to impact on daily activities. A diagnosis of Alzheimer's disease could only be made after exclusion of other possible causes. 1 Sixty-five to 80% of cases of patients fulfilling these criteria have Alzheimer's pathology (plaques and tangles), the remainder having a range of other pathologies. In order to increase diagnostic certainty, contemporary criteria for AD dementia incorporate biomarker evidence for different aspects of Alzheimer's pathology, including imaging (magnetic resonance imaging -MRI -measures of atrophy; 18 F-fluorodeoxyglucose-positron emission tomography -FDG-PET -measures of cerebral hypometabolism; amyloid PET measures of fibrillar β-amyloid -A -deposition) and cerebrospinal fluid -CSF (decreased levels of A42, increased levels of tau and phospho-tau). 2,3 Alzheimer's disease process. Recognizing that AD pathology is present many years before symptoms emerge, new criteria classify the disease process on a continuum from asymptomatic to prodromal and finally to dementia stage. 4 Individuals at the asymptomatic stage can only be identified by biomarkers of Alzheimer's pathology. None...

Data-driven approaches for Tau-PET imaging biomarkers in Alzheimer’s disease

“…18 F]AV1451 signal [42][43][44] . As such, even small improvements are important for studies assessing more subtle effects of cortical tau accumulation and studies seeking optimal biomarkers for multimodal classification or disease progression 45 .…”

The emerging roles of protein homeostasis‐governing pathways in Alzheimer's disease

“…As the most prevalent cause of dementia (accounting for nearly 70% of newly diagnosed dementia cases), Alzheimer's disease afflicted approximately 50 million patients globally in 2015 which is expected to rise to 115 million by the middle of 21st century, affecting half of the elderly population over 85 years old (Guo, Cheng, North, & Wei, 2017). Moreover, the number of early‐onset cases (those diagnosed with AD under the age of 65) has reached approximately 200,000 in the United States, indicating an intense urgency for better early identification methods and clinical management of Alzheimer's disease (Frisoni, Boccardi, Barkhof, Blennow, & Cappa, 2017; Guo, Cheng et al., 2017). …”

Brain FDG-PET: clinical use in dementing neurodegenerative conditions

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