About this Research Topic
AD lacks effective treatments to modify disease progression. So far, three main therapeutic strategies have been described: 1) targeted brain amyloid deposition and accumulation (either by preventing or removing); 2) reduction of neurofibrillary tangles; or 3) acting on other disease-associated mechanisms. In view of the continued failure on anti-AD drug development targeting Aβ and Tau, other molecular mechanisms have been proposed. Neuroinflammation has been an emerging mechanism allowing drug development, an idea that is increasing in traction. Over the past years, studies have identified new molecular mechanisms and modifiable risk factors, changing AD’s neuropathology. For instance, the neuroinflammation underlying AD has been further elucidated and different strategies have been designed for AD intervention. Furthermore, roles of aging in the progression of AD are emerging as a field of particular interest; for example, age-dependent reduction of autophagy/mitophagy as well as NAD+ depletion, may play a causative role in AD.
Accumulative data suggest that advancing the understanding of AD mechanisms and risk factors may allow the development of targeted interventions to potentially prevent or cure the disease. There is an increasing number of mechanism-driven therapies effective in reducing the disease neuropathology in preclinical models, including AD transgenic models (e.g. the 5XFAD animals harboring amyloid neuropathology) and 3D human neural culture models. Among several examples, Cromolyn has gained attention as a small molecule in testing trials. Cromolyn has been tested for its mechanism of action, modulating neuroinflammation in cell and animal preclinical models and is currently in a Phase-III trial of AD. NAD+ is reduced in the brain of AD patients and a clinical trial is in preparation on an NAD+-boosting strategy to treat AD. These recent results highlight the need to deepen our knowledge and develop preclinical studies that are valuable resources and will require further testing for disease management in humans.
This Research Topic aims to collect experimental evidence supporting the facilitation of preclinical discoveries into clinical development. In particular, this topic will not only cover promising interventions, but also report and shed light on the areas that can further the disease understanding and future potential intervention strategies. We welcome Original Research articles and timely Reviews.
Areas of focus will include:
1. Recent findings on genetics, biofluid or molecule imaging-based biomarkers of AD, including those involving neuro-immunity and metabolism.
2. Evidence and reports on novel drug discoveries and drug targets identified from genetics and biomarker studies
3. Novel research methods to improve disease pathogenesis and progression, including molecular imaging, 3D modelling/printing and brain connectome.
Topic Editor Dr. Evandro Fei Fang has CRADA arrangements with ChromaDex, and is a consultant to Aladdin Healthcare Technologies and the Vancouver Dementia Prevention Centre. All other Topic Editors declare no competing interests with regards to the Research Topic subject.
Keywords: Alzheimer's Disease, translational medicine, aging, neurodegeneration, neuropathology
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