About this Research Topic
Currently, Alzheimer’s disease is the most common form of dementia affecting more than 50 million people globally. Alzheimer’s disease is a chronic neurodegenerative disorder that is characterized by memory impairment, cognitive dysfunction and behavioral disturbances. This disease is caused by severe neuronal loss especially in the hippocampus and associated neocortical regions, but the mechanism underlying neuronal death has been unknown for more than a century. For nearly three decades, amyloid β peptides were believed to be the principal cause of neuronal death, but the biomolecular role of amyloid β has not been elucidated in detail. For example, it still remains unelucidated 1) why pathological levels of Aβ are present in cognitively normal individuals, 2) Why some individuals clinically diagnosed with Alzheimer do not have Aβ pathology, but exhibit non-Aβ pathologies, and 3) Why the spatial appearance, progression and absolute amount of amyloid plaques do not always correlate with declining cognition. Of particular importance is the observation that clinical trials for anti-amyloid therapies in humans have been largely unsuccessful, and as such, it is imperative that new research strategies are explored.
Because of the less significant correlations between the extent of amyloid β deposition and either degree of synapse pathology, neuronal loss or dementia, we are now obliged to conclude that the ‘amyloid β hypothesis’ has become less reliable. Most researchers still place Aβ as central to Alzheimer's disease, although the many possible Aβ-independent disease pathways could also be involved. Since the brain is rich in polyunsaturated fatty acids and harbors a relatively high concentration of oxygen in the lipid bilayer, oxidative stress-induced lipid peroxidation and accumulation of aldehyde products may also be a key factor in neurodegeneration. In this Research Topic, we raise critical questions regarding the role of Aβ in the diagnosis, pathogenesis, and therapeutic strategies for Alzheimer’s disease, as well as consider how oxidative stress, brain ischemia, and alcohol may be implicated.
To this aim, we welcome both Original Research and Review articles focused on the following aspects:
1) New data surrounding the accuracy of current consensus diagnostic criteria for Alzheimer’s disease and the validity of the amyloid hypothesis supporting them.
2) Research into treatment, prediction, diagnosis and etiology in clinically identified Alzheimer subjects irrespective of risk factors.
3) Future investment in longitudinal biomarkers such as neuroinflammation, vascular factors, lipid peroxidation, and synaptic/neurodegeneration markers.
4) Studies of the mechanistic drivers underlying synapse dysfunction and loss.
Because of the less significant correlations between the extent of amyloid β deposition and either degree of synapse pathology, neuronal loss or dementia, we are now obliged to conclude that the ‘amyloid β hypothesis’ has become less reliable. Most researchers still place Aβ as central to Alzheimer's disease, although the many possible Aβ-independent disease pathways could also be involved. Since the brain is rich in polyunsaturated fatty acids and harbors a relatively high concentration of oxygen in the lipid bilayer, oxidative stress-induced lipid peroxidation and accumulation of aldehyde products may also be a key factor in neurodegeneration. In this Research Topic, we raise critical questions regarding the role of Aβ in the diagnosis, pathogenesis, and therapeutic strategies for Alzheimer’s disease, as well as consider how oxidative stress, brain ischemia, and alcohol may be implicated.
To this aim, we welcome both Original Research and Review articles focused on the following aspects:
1) New data surrounding the accuracy of current consensus diagnostic criteria for Alzheimer’s disease and the validity of the amyloid hypothesis supporting them.
2) Research into treatment, prediction, diagnosis and etiology in clinically identified Alzheimer subjects irrespective of risk factors.
3) Future investment in longitudinal biomarkers such as neuroinflammation, vascular factors, lipid peroxidation, and synaptic/neurodegeneration markers.
4) Studies of the mechanistic drivers underlying synapse dysfunction and loss.
Keywords: amyloid hypothesis, Alzheimer's disease, dementia, lipid peroxidation, aldehyde, oxidative stress, alcohol, brain ischemia
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