Amyloid β protein (Aβ) is the main component of neuritic plaques in Alzheimer's disease (AD), and its accumulation has been considered as the molecular driver of Alzheimer's pathogenesis and progression. Aβ has been the prime target for the development of AD therapy. However, the repeated failures of Aβ-targeted clinical trials have cast considerable doubt on the amyloid cascade hypothesis and whether the development of Alzheimer's drug has followed the correct course. However, the recent successes of Aβ targeted trials have assuaged those doubts. In this review, we discussed the evolution of the amyloid cascade hypothesis over the last 30 years and summarized its application in Alzheimer's diagnosis and modification. In particular, we extensively discussed the pitfalls, promises and important unanswered questions regarding the current anti-Aβ therapy, as well as strategies for further study and development of more feasible Aβ-targeted approaches in the optimization of AD prevention and treatment. 

/pdf/amyloid-b-based-therapy-for-alzheimers-disease-challenges-28xmf2dn.pdf

Amyloid β-based therapy for Alzheimer’s disease: challenges, successes and future

Alzheimer's disease (AD) is the most common neurodegenerative disease. Pathological proteins of AD mainly contain amyloid-beta (Aβ) and tau. Their deposition will lead to neuron damage by a series of pathways, and then induce memory and cognitive impairment. Thus, it is pivotal to understand the clearance pathways of Aβ and tau in order to delay or even halt AD. Aβ clearance mechanisms include ubiquitin-proteasome system, autophagy-lysosome, proteases, microglial phagocytosis, and transport from the brain to the blood via the blood-brain barrier (BBB), arachnoid villi and blood-CSF barrier, which can be named blood circulatory clearance. Recently, lymphatic clearance has been demonstrated to play a key role in transport of Aβ into cervical lymph nodes. The discovery of meningeal lymphatic vessels is another direct evidence for lymphatic clearance in the brain. Furthermore, periphery clearance also contributes to Aβ clearance. Tau clearance is almost the same as Aβ clearance. In this review, we will mainly introduce the clearance mechanisms of Aβ and tau proteins, and summarize corresponding targeted drug therapies for AD.

Clearance of Amyloid Beta and Tau in Alzheimer’s Disease: from Mechanisms to Therapy

Alzheimer’s disease (AD) is the most common type of dementia, and no disease-modifying treatments are available to halt or slow its progression. Amyloid-beta (Aβ) is suggested to play a pivotal role in the pathogenesis of AD, and clearance of Aβ from the brain becomes a main therapeutic strategy for AD. Recent studies found that Aβ clearance in the periphery contributes substantially to reducing Aβ accumulation in the brain. Therefore, understanding the mechanism of how Aβ is cleared in the periphery is important for the development of effective therapies for AD. In this review, we summarized recent findings on the mechanisms of Aβ efflux from the brain to the periphery and discuss where and how the brain-derived Aβ is cleared in the periphery. Based on these findings, we propose future strategies to enhance peripheral Aβ clearance for the prevention and treatment of AD. This review provides a novel perspective to understand the pathogenesis of AD and develop interventions for this disease from a systemic approach.

/pdf/peripheral-clearance-of-brain-derived-ab-in-alzheimer-s-eoje8ddd95.pdf

Peripheral clearance of brain-derived Aβ in Alzheimer's disease: pathophysiology and therapeutic perspectives

Understanding preanalytical variables and their effects on clinical biomarkers of oncology and immunotherapy.

Cryopreservation-related loss of antigen-specific IFNγ producing CD4+ T-cells can skew immunogenicity data in vaccine trials: Lessons from a malaria vaccine trial substudy.

https://biblio.ugent.be/publication/5864950/file/5864971.pdf

Processing of blood samples influences PBMC viability and outcome of cell-mediated immune responses in antiretroviral therapy-naïve HIV-1-infected patients.

Methods to monitor monocytes-mediated amyloid-beta uptake and phagocytosis in the context of adjuvanted immunotherapies.

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Processing of blood samples influences PBMC viability and outcome of cell-mediated immune responses in antiretroviral therapy-naïve HIV-1-infected patients.

Methods to monitor monocytes-mediated amyloid-beta uptake and phagocytosis in the context of adjuvanted immunotherapies.