Dear Editors,Alzheimer’s disease(AD)and vascular dementia(VaD)are two of the most common forms of dementia,resulting in increased disability and mortality,impaired quality of life,and serious burdens on society and caregivers.However,the presently available drugs can only alleviate symptoms for a short time without delaying the progression of the cognitive disorders.Since 2003,no new drugs have been approved by the US Food and Drug Administration for the treatment of AD.In 2019,phase III clinical trials of crenezumab and aducanumab,two anti-amyloid beta monoclonal antibodies,were terminated.The scant progress in clinical trials urges efforts towards an alternative therapeutic strategy for dementia.
Yi XiePei-Pei LiuYa-Jun LianHong-Bo LiuJian-Sheng Kang
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.
