Curated Papers > Recent high-impact research on "Alzheimer's Disease" (IF≥30, last 5 years)

Is Alzheimer disease a disease?

Literature Information

DOI	10.1038/s41582-024-00940-4
PMID	38424454
Journal	Nature reviews. Neurology
Impact Factor	33.1
JCR Quartile	Q1
Publication Year	2024
Times Cited	53
Keywords	Alzheimer disease, neurodegenerative disease, amyloid-β, neurofibrillary tangles, multifaceted treatment
Literature Type	Journal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural
ISSN	1759-4758
Pages	245-251
Issue	20(4)
Authors	Amos D Korczyn, Lea T Grinberg

TL;DR

This research highlights the complexity of Alzheimer's disease (AD), emphasizing that its multifactorial nature—shaped by various genetic, environmental, and clinical factors—suggests it functions more as a syndrome than a singular illness. The study argues for a comprehensive treatment approach rather than reliance on a single solution, underscoring the need for improved recognition and classification of conditions associated with amyloid-β plaques and tau tangles to advance therapeutic strategies.

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Alzheimer disease · neurodegenerative disease · amyloid-β · neurofibrillary tangles · multifaceted treatment

Abstract

Dementia, a prevalent condition among older individuals, has profound societal implications. Extensive research has resulted in no cure for what is perceived as the most common dementing illness: Alzheimer disease (AD). AD is defined by specific brain abnormalities - amyloid-β plaques and tau protein neurofibrillary tangles - that are proposed to actively influence the neurodegenerative process. However, conclusive evidence of amyloid-β toxicity is lacking, the mechanisms leading to the accumulation of plaques and tangles are unknown, and removing amyloid-β has not halted neurodegeneration. So, the question remains, are we making progress towards a solution? The complexity of AD is underscored by numerous genetic and environmental risk factors, and diverse clinical presentations, suggesting that AD is more akin to a syndrome than to a traditional disease, with its pathological manifestation representing a convergence of pathogenic pathways. Therefore, a solution requires a multifaceted approach over a single 'silver bullet'. Improved recognition and classification of conditions that converge in plaques and tangle accumulation and their treatment requires the use of multiple strategies simultaneously.

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Primary Questions Addressed

1. What are the key differences between Alzheimer's disease and other forms of dementia?
2. How do genetic and environmental factors contribute to the development of Alzheimer's disease?
3. In what ways could the classification of Alzheimer's disease as a syndrome change treatment approaches?
4. What are the current research directions aimed at understanding the mechanisms behind amyloid-β accumulation?
5. How can a multifaceted approach improve the management and treatment outcomes for Alzheimer's disease patients?

Key Findings

Research Background and Purpose

Dementia, particularly Alzheimer disease (AD), is a major health concern among the elderly, characterized by specific brain abnormalities such as amyloid-β plaques and tau neurofibrillary tangles. Despite extensive research, there is currently no cure for AD, and the exact mechanisms behind plaque and tangle accumulation remain unclear. The purpose of this research is to explore the complexity of AD, emphasizing the need for a multifaceted approach to treatment rather than a single solution.

Main Methods/Materials/Experimental Design

The study employs a comprehensive review of existing literature and research findings to analyze the various genetic and environmental risk factors associated with AD. The research design focuses on understanding the multifactorial nature of AD and the convergence of different pathogenic pathways.

Key Results and Findings

• Complexity of AD: The research highlights that AD should be viewed as a syndrome due to its diverse clinical presentations and the interplay of multiple risk factors.
• Amyloid-β Toxicity: There is a lack of conclusive evidence supporting the toxicity of amyloid-β, raising questions about its role in neurodegeneration.
• Pathogenic Pathways: The study emphasizes the need to better understand the mechanisms leading to the accumulation of plaques and tangles, suggesting that multiple strategies are necessary for effective treatment.

Main Conclusions/Significance/Innovation

The findings underscore the importance of recognizing AD as a complex condition requiring a multifaceted treatment approach. The study advocates for improved classification of conditions related to amyloid-β and tau pathology, highlighting the necessity of simultaneous strategies to address the diverse manifestations of AD. This perspective may lead to more effective therapeutic interventions in the future.

Research Limitations and Future Directions

• Limitations: The study is primarily a literature review, which may limit the applicability of findings to clinical practice without empirical data to support proposed strategies.
• Future Directions: Further research is needed to explore the underlying mechanisms of amyloid-β and tau accumulation, as well as to develop and test integrated treatment strategies that address the multifactorial nature of AD. Future studies should focus on longitudinal analyses to track the progression of AD and the efficacy of proposed interventions.

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Literatures Citing This Work

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... (43 more literatures)

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