Biomarkers for Alzheimer’s Disease

Abstract

Alzheimer´s disease (AD) and related forms of dementia are increasingly affecting the aging population throughout the world, at an alarming rate. The World Alzheimer´s Report indicates a prevalence of 46.8 million people affected by AD worldwide. As population ages, this number is projected to triple by 2050 unless effective interventions are developed and implemented. Urgent efforts are required for an early detection of this disease. The ultimate goal is the identification of viable targets for the development of molecular markers and validation of their use for early diagnosis of AD that may improve treatment and the disease outcome in patients. The diagnosis of AD has been difficult to resolve since approaches for early and accurate detection and follow-up of AD patients at the clinical level have been reported only recently. Some proposed AD biomarkers include the detection of pathophysiological processes in the brain in vivo with new imaging techniques and novel PET ligands, and the determination of pathogenic proteins in cerebrospinal fluid showing anomalous levels of hyperphosphorylated tau and low Aβ peptide. These biomarkers have been increasingly accepted by AD diagnostic criteria and are important tools for the design of clinical trials, but difficulties in accessibility to costly and invasive procedures have not been completely addressed in clinical settings. New biomarkers are currently being developed to allow determinations of multiple pathological processes including neuroinflammation, synaptic dysfunction, metabolic impairment, protein aggregation and neurodegeneration. Highly specific and sensitive blood biomarkers, using less-invasive procedures to detect AD, are derived from the discoveries of peripheric tau oligomers and amyloid variants in human plasma and platelets. We have also developed a blood tau biomarker that correlates with a cognitive decline and also with neuroimaging determinations of brain atrophy.

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“…45 Subjects will be registered in generation study 1 (cohort 1: CAD106 or placebo, cohort 2: umibecestat or placebo) or generation study 2 (umibecestat 50 and 15 mg, or placebo). 45 ABvac40 is evaluated in a phase 2 study, as the first active vaccine against the C-terminal end of Aβ 40 . A phase 1 study was conducted with patients with mild to moderate AD aged 50 to 85 years.…”

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“…As blood is more accessible than CSF, potential biomarkers have largely been studied in this biological fluid [54,55]. Apart from the much less invasive procedure of blood collection as…”

“…As blood is more accessible than CSF, potential biomarkers have largely been studied in this biological fluid [54,55]. Apart from the much less invasive procedure of blood collection as compared to the lumbar puncture, it allows repeated sampling and measurements to monitor the AD progression or to evaluate the efficacy of the newly developed drugs during clinical trials.…”