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- Title
Paradigm shift from diagnosing patients based on common symptoms to categorizing patients into subtypes with different pathogenic mechanisms to guide treatment for Alzheimer's disease.
- Authors
Keiro Shirotani; Masashi Asai; Nobuhisa Iwata
- Abstract
Alzheimer's disease (AD) is a major cause of dementia in the elderly, and the number of AD patients is rapidly growing as life expectancy increases. However, diseasemodifying drugs are not yet available. According to the amyloid hypothesis, disease onset is triggered by aggregation and accumulation of amyloid-b peptide, followed by the formation of neurofibrillary tangles composed of hyperphosphorylated tau, and synaptic loss/neuronal cell death leading to dementia. Based on this hypothesis, various clinical trials for treatment of AD have been conducted, but most were discontinued due to failure to achieve cognitive improvement or appearance of adverse effects. Here we discuss the reasons for the failure of these trials. We suggest that biomarkers of specific, distinct molecular mechanisms of amyloidogenesis should be developed concomitantly with diseasemodifying drugs (the so-called companion diagnosis) to aid the proper design of clinical trials, as well as to enable personalized treatment of individual AD patients.
- Subjects
ALZHEIMER'S disease diagnosis; ALZHEIMER'S disease treatment; AMYLOID; NEUROFIBRILLARY tangles; SYMPTOMS
- Publication
Journal of Biochemistry, 2017, Vol 161, Issue 6, p463
- ISSN
0021-924X
- Publication type
Article
- DOI
10.1093/jb/mvx015