Abstract
Dementia is currently diagnosed based on clinical symptoms and signs, but significant brain damage has already occurred by the time a clinical diagnosis of dementia is made, and it is increasingly recognized that this may be too late for any effective intervention. It would therefore be of great public health and preventive value to define a variety of biomarkers that could permit early detection of persons at a higher risk for developing dementia, and specifically dementia due to Alzheimer’s disease. Nevertheless, for the purpose of large-scale screening, circulating biomarkers are more appropriate because they are less invasive than lumbar puncture, less costly than brain amyloid imaging and can be easily assessed repeatedly in a primary care clinic setting. In this brief review we will review a number of candidate molecules implicated as possible predictors of dementia risk. These candidates include markers of vascular injury, metabolic and inflammatory states, amyloid and tau pathway markers, measures of neural degeneration and repair efforts, and other molecules that might contribute to anatomical and functional changes characteristic of dementia and Alzheimer’s disease.
Highlights
The lifetime risk of dementia is one in five [1], with an estimated prevalence of 24 million people worldwide
Dementia is diagnosed based on clinical characteristics [3,4] but brain imaging and cerebrospinal fluid (CSF) markers are thought to improve diagnostic sensitivity and specificity, especially with regard to the etiology of the dementia [5]
Significant brain damage has already occurred by the time a clinical diagnosis of dementia is made, and it is increasingly recognized that this may be too late for any effective intervention
Summary
The lifetime risk of dementia is one in five [1], with an estimated prevalence of 24 million people worldwide. Other promising biomarkers A variety of other plasma proteins seems promising and merit further study These candidates include: proteins linked to AD pathophysiological processes (such as beta-site amyloid precursor protein-cleaving enzyme 1, transthyretin, butyrylcholinesterase and choline acetyltransferase); markers of neuronal injury (such as neuron-specific enolase), of astroglial injury (glial fibrillary acid protein), of oligodendroglial injury (S-100), of myelin injury (such as myelin basic protein), and of endothelial and matrix function (such as vascular endothelial growth factor and matrix metallopeptidase-9); levels of vitamins, such as vitamin D (lower levels of which have been associated with risk of cardiovascular disease, cognitive decline and with prevalent but not incident dementia) [129] and vitamin E; neurotrophic factors that are involved in neuronal growth, development and synaptic plasticity and whose circulating levels change with lifestyle (diet and physical activity), for example brain-derived neurotrophic factor, beta-nerve growth factor and insulinlike growth factor-1; and protein products of genes identified via genome-wide association studies and candidate gene studies. Another paper used data-mining approaches to the published literature and identified five likely candidates including a novel one, urokinase-type plasminogen activator receptor [133]
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