Currently Available Biomarkers and Strategies for the Validation of Novel Candidates for Neurochemical Dementia Diagnostics in Alzheimer’s Disease and Mild Cognitive Impairment
The number of people afflicted with Alzheimer’s disease (AD) and other types of dementing conditions has grown exponentially in the last decades. This review focuses on the diagnostic role of the classic cerebrospinal fluid (CSF) biomarkers of neurochemical dementia diagnostics (NDD) and critically discusses potential strategies for the development and validation of novel potential candidates. In some countries, NDD is already established as a routine diagnostic tool, used for the evaluation of patients with cognitive impairments. On the other hand, preanalytical and technical issues, partly discussed in this paper, prevent NDD from the general acceptance worldwide. Currently, two groups of biomarkers in the CSF are considered in NDD: amyloid β (Aβ) peptides and Tau proteins, including the hyperphosphorylated forms of the latter (pTau). The analyses of these two groups of biomarkers can reveal pathologic alterations as early as twenty years before the onset of clinical symptoms. In mild cognitive impairment (MCI), NDD can reliably predict which individuals are at risk of converting to AD. The roles of biomarkers of amyloid β deposition in the brain tissue (including the CSF concentration of Aβ42) and biomarkers of neurodegeneration (including the CSF concentrations of Tau/pTau proteins) are reflected in the currently proposed diagnostic criteria for AD and MCI. 1. Introduction: Alzheimer’s Disease versus Alzheimer’s Dementia The number of people with Alzheimer’s disease (AD) and other types of dementing conditions has drastically increased over the last decades. Approximately 14 million people in Europe and the USA are currently afflicted by AD, including more than 40% of the population over the age of 85 years [1, 2]. In the USA, AD is the seventh leading cause of death, and the annual costs associated with this disease in 2010 were $172 billion in the USA and over $600 billion worldwide [3]. Moreover, dementing conditions cause a tremendous burden for the relatives of the afflicted patients; in 2010, nearly 15 million family members and other unpaid caregivers provided an estimated 17 billion hours of care for people with AD and other dementias [2]. The discovery of drugs that could treat this devastating condition would undoubtedly represent a breakthrough in medicine. However, to achieve this goal, it is important to have diagnostic tools that are capable of correctly discriminating patients and preferentially in the earliest preclinical stages. It is also important to precisely define what is being discussed; that is, it is important to realize
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