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History and progress of hypotheses and clinical trials for Alzheimer’s disease
Open accessAbstract
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive memory loss along with neuropsychiatric symptoms and a decline in activities of daily life. Its main pathological features are cerebral atrophy, amyloid plaques, and neurofibrillary tangles in the brains of patients. There are various descriptive hypotheses regarding the causes of AD, including the cholinergic hypothesis, amyloid hypothesis, tau propagation hypothesis, mitochondrial cascade hypothesis, calcium homeostasis hypothesis, neurovascular hypothesis, inflammatory hypothesis, metal ion hypothesis, and lymphatic system hypothesis. However, the ultimate etiology of AD remains obscure. In this review, we discuss the main hypotheses of AD and related clinical trials. Wealthy puzzles and lessons have made it possible to develop explanatory theories and identify potential strategies for therapeutic interventions for AD. The combination of hypometabolism and autophagy deficiency is likely to be a causative factor for AD. We further propose that fluoxetine, a selective serotonin reuptake inhibitor, has the potential to treat AD.
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“AD can be categorized into two main types: familial (accounting for 1-5% of AD cases) and sporadic forms (over 95% of cases).76”
From Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies. (2024) · cites this paper as [76]
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“The most prevalent hypotheses are the Aβ cascade hypothesis, the inflammation hypothesis, the cholinergic hypothesis, the tau hypothesis, and the oxidative hypothesis [18,19,20].”
From The Multifaceted Role of Neuroprotective Plants in Alzheimer’s Disease Treatment (2022) · cites this paper as [20]
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Metadata
- Authors
- Liu, P.-P., Xie, Y., Meng, X.-Y., & Kang, J.-S.
- Affiliations
- First Affiliated Hospital of Zhengzhou University (CN)
- Corresponding author
- Kang, Jian-Sheng
- Venue
- Signal Transduction and Targeted Therapy
- Published
- 2019-08-23
- Volume
- 4
- Issue
- 1
- Pages
- 29-29
- ISSN
- 2059-3635 (ISSN-L)
- PMC
- PMC6799833
- OpenAlex
- W2969562288
- Cited by
- 723
- References
- 473
- Citations by year
- 2026: 54 · 2025: 94 · 2024: 146 · 2023: 124 · 2022: 130 · 2021: 106 · 2020: 66 · 2019: 3
- FWCI
- 9.02
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-09-23)
- Open access
- gold
- doi.org
- Locations
- Signal Transduction and Targeted Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Natural Science Foundation of China (31171369)
- the Chinese Academy of Sciences
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid hypothesis, cholinergic hypothesis, neuroinflammation, calcium homeostasis, brain hypometabolism, autophagy dysfunction, fluoxetine, selective serotonin reuptake inhibitors, clinical trials, therapeutic interventions
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