Abstract
ABSTRACTThe neurodegenerative disorder Alzheimer's disease is characterised by the formation of β-amyloid plaques and neurofibrillary tangles in the brain parenchyma, which cause synapse and neuronal loss. This leads to clinical symptoms, such as progressive memory deficits. Clinically, these pathological changes can be detected in the cerebrospinal fluid and with brain imaging, although reliable blood tests for plaque and tangle pathologies remain to be developed. Plaques and tangles often co-exist with other brain pathologies, including aggregates of transactive response DNA-binding protein 43 and Lewy bodies, but the extent to which these contribute to the severity of Alzheimer's disease is currently unknown. In this ‘At a glance’ article and poster, we summarise the molecular biomarkers that are being developed to detect Alzheimer's disease and its related pathologies. We also highlight the biomarkers that are currently in clinical use and include a critical appraisal of the challenges associated with applying these biomarkers for diagnostic and prognostic purposes of Alzheimer's disease and related neurodegenerative disorders, also in their prodromal clinical phases.
Highlights
Neurodegenerative dementias constitute a broad category of brain diseases that are characterised by a typically gradual decline in cognitive function, leading to increased mortality
Because clinical phenotypes of dementia can be caused by different pathological changes, sometimes interacting with each other, it is important to develop biomarkers that can diagnose these changes to improve the possibility to monitor and treat the underlying cause. In this ‘At a glance’ poster, we show the different neuropathological changes that might underlie neurodegenerative dementias, especially Alzheimer’s disease (AD), and discuss the currently available molecular fluid- and imaging-based biomarkers for each pathology
P-tau concentration in the cerebrospinal fluid (CSF) correlates weakly with neurofibrillary tangle pathology in the brain of AD patients (Buerger et al, 2006; Seppala et al, 2012). This finding was replicated in a recent tau positron emission tomography (PET) imaging study of AD patients (Chhatwal et al, 2016), the results are less clear than the association of CSF Aβ42 with amyloid PET
Summary
Neurodegenerative dementias constitute a broad category of brain diseases that are characterised by a typically gradual decline in cognitive function, leading to increased mortality. These pathological changes can be detected in the cerebrospinal fluid and with brain imaging, reliable blood tests for plaque and tangle pathologies remain to be developed.
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