scholarly journals The past, present, and future of disease-modifying therapies for Alzheimer’s disease

2017 ◽  
Vol 93 (10) ◽  
pp. 757-771 ◽  
Author(s):  
Kazushi SUZUKI ◽  
Atsushi IWATA ◽  
Takeshi IWATSUBO
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
The Past ◽  
Disease Modifying Therapies ◽  
Disease Modifying

scholarly journals Astrocytic transporters in Alzheimer's disease

2017 ◽  
Vol 474 (3) ◽  
pp. 333-355 ◽  
Author(s):  
Chris Ugbode ◽  
Yuhan Hu ◽  
Benjamin Whalley ◽  
Chris Peers ◽  
Marcus Rattray ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Neurological Diseases ◽  
Current Evidence ◽  
Specific Targeting ◽  
Disease Modifying Therapies ◽  
The Central Nervous System ◽  
Disease Modifying ◽  
And Function

Astrocytes play a fundamental role in maintaining the health and function of the central nervous system. Increasing evidence indicates that astrocytes undergo both cellular and molecular changes at an early stage in neurological diseases, including Alzheimer's disease (AD). These changes may reflect a change from a neuroprotective to a neurotoxic phenotype. Given the lack of current disease-modifying therapies for AD, astrocytes have become an interesting and viable target for therapeutic intervention. The astrocyte transport system covers a diverse array of proteins involved in metabolic support, neurotransmission and synaptic architecture. Therefore, specific targeting of individual transporter families has the potential to suppress neurodegeneration, a characteristic hallmark of AD. A small number of the 400 transporter superfamilies are expressed in astrocytes, with evidence highlighting a fraction of these are implicated in AD. Here, we review the current evidence for six astrocytic transporter subfamilies involved in AD, as reported in both animal and human studies. This review confirms that astrocytes are indeed a viable target, highlights the complexities of studying astrocytes and provides future directives to exploit the potential of astrocytes in tackling AD.

scholarly journals Fleshing out the amyloid cascade hypothesis: the molecular biology of Alzheimer's disease

2000 ◽  
Vol 2 (2) ◽  
pp. 101-110 ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Biology ◽  
Basic Science ◽  
Amyloid Protein ◽  
Amyloid Cascade Hypothesis ◽  
Protein Tau ◽  
Disease Modifying Therapies ◽  
Disease Modifying ◽  
Amyloid Cascade

Alzheimer's disease (AD) is a disorder of two pathologies- plaques and tangles. The former have as a key constituent amyloid protein and the latter the microtubule-associaied protein tau. Genetics has demonstrated that changes in either protein are sufficient to cause dementia. The amyloid cascade hypothesis proposes that plaque-related changes precede tangle-related changes and positions amyloid as central to the degeneration of AD. All the evidence suggests this is correct, including evidence that presenil ins alter the processing of the amyloid precursor protein and evidence that disrupting the normal properties of tau underlies the related froniotemporal dementias. The amyloid cascade hypothesis has provided the basis for nearly a decade of intensive basic science - the skeleton of that hypothesis can now be fleshed out, and confidence is growing that this will result in useful disease-modifying therapies in the future.

Does protein aggregation drive postmitotic tissue degeneration?

2021 ◽  
Vol 13 (577) ◽  
pp. eaax0914 ◽  
Author(s):  
Jeffery W. Kelly
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Protein Aggregation ◽  
Protein Aggregate ◽  
Tissue Degeneration ◽  
Disease Modifying Therapies ◽  
Disease Modifying ◽  
Amyloid Diseases ◽  
Aggregate Structures

Pharmacological evidence, from clinical trials where patients with systemic amyloid diseases are treated with disease-modifying therapies, supports the notion that protein aggregation drives tissue degeneration in these disorders. The protein aggregate structures driving tissue pathology and the commonalities in etiology between these diseases and Alzheimer’s disease are under investigation.

REPORT FROM THE FIRST CLINICAL TRIALS ON ALZHEIMER’S DISEASE (CTAD) ASIA-CHINA 2018 : BRINGING TOGETHER GLOBAL LEADERS

2019 ◽  
pp. 1-4
Author(s):  
J.K. Chhetri ◽  
P. Chan ◽  
B. Vellas ◽  
J. Touchon ◽  
S. Gauthier
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Chinese Population ◽  
The West ◽  
Disease Modifying Therapies ◽  
Increased Risk ◽  
Disease Modifying ◽  
Past Experiences

Population of older adults in Asia, and particularly in China is increasing rapidly. Older population are at increased risk of Alzheimer’s disease (AD) and other dementias. Soon, the Chinese population with AD will represent almost half of the world’s AD population. There is a desperate need of disease modifying therapies to delay or slow the progression of AD, to tackle this emerging healthcare emergency. In this context, the first CTAD Asia-China conference was held in China to bring together Western and Asian leaders in AD. This meeting focused largely on how to develop successful trials in China, utilizing past experiences from the West.

scholarly journals BIOMARKER AND CLINICAL TRIAL DESIGN SUPPORT FOR DISEASE-MODIFYING THERAPIES: REPORT OF A SURVEY OF THE EU/US: ALZHEIMER’S DISEASE TASK FORCE

2018 ◽  
pp. 1-7
Author(s):  
J. Cummings ◽  
N. Fox ◽  
B. Vellas ◽  
P. Aisen ◽  
G. Shan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trial ◽  
Trial Design ◽  
Task Force ◽  
Clinical Trial Design ◽  
Disease Modification ◽  
Disease Modifying Therapies ◽  
Disease Modifying ◽  
The Eu

BACKGROUND: Disease-modifying therapies are urgently needed for the treatment of Alzheimer’s disease (AD). The European Union/United States (EU/US) Task Force represents a broad range of stakeholders including biopharma industry personnel, academicians, and regulatory authorities. OBJECTIVES: The EU/US Task Force represents a community of knowledgeable individuals who can inform views of evidence supporting disease modification and the development of disease-modifying therapies (DMTs). We queried their attitudes toward clinical trial design and biomarkers in support of DMTs. DESIGN/SETTING/PARTICIANTS: A survey of members of the EU/US Alzheimer’s Disease Task Force was conducted. Ninety-three members (87%) responded. The details were analyzed to understand what clinical trial design and biomarker data support disease modification. MEASUREMENTS/RESULTS/CONCLUSIONS: Task Force members favored the parallel group design compared to delayed start or staggered withdrawal clinical trial designs to support disease modification. Amyloid biomarkers were regarded as providing mild support for disease modification while tau biomarkers were regarded as providing moderate support. Combinations of biomarkers, particularly combinations of tau and neurodegeneration, were regarded as providing moderate to marked support for disease modification and combinations of all three classes of biomarkers were regarded by a majority as providing marked support for disease modification. Task Force members considered that evidence derived from clinical trials and biomarkers supports clinical meaningfulness of an intervention, and when combined with a single clinical trial outcome, nearly all regarded the clinical trial design or biomarker evidence as supportive of disease modification. A minority considered biomarker evidence by itself as indicative of disease modification in prevention trials. Levels of evidence (A,B,C) were constructed based on these observations. CONCLUSION: The survey indicates the view of knowledgeable stakeholders regarding evidence derived from clinical trial design and biomarkers in support of disease modification. Results of this survey can assist in designing clinical trials of DMTs.

Challenges in demonstrating the value of disease-modifying therapies for Alzheimer’s disease

2020 ◽  
Vol 20 (6) ◽  
pp. 563-570 ◽  
Author(s):  
Anders Gustavsson ◽  
Peter Pemberton-Ross ◽  
Melissa Gomez Montero ◽  
Mahmoud Hashim ◽  
Robin Thompson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Modifying Therapies ◽  
Disease Modifying
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