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It seems that how Alzheimer's disease occurs and how to choose treatment has always been a problem for countless people. It is not only a logical problem of chicken or egg first, but also a philosophical problem of appearance and essence. In addition to the treatment dilemma that makes scientists scratch their heads, clinicians helpless and the general public sad, it also reflects the time trauma that aging brings to everyone. With doubts, the exploration is still going on. Donanemab, a therapeutic drug for amyloid β-protein (Aβ), announced the results of its phase Ⅱ study in patients with early symptoms of Alzheimer's disease. Patients received Donanemab intravenously every four weeks. At 76 weeks, the baseline change of Alzheimer's rating scale (iADRS; Range, 0-144, lower score, indicating that cognitive dysfunction is more serious) score was - 6.86, and that of the placebo group was - 10.6 (the difference was 3.20 [95% CI: 0.12-6.27; p=0.04). Most of the secondary endpoints, such as clinical dementia scale (CDR-SB), 13 item cognitive subscale of Alzheimer's assessment scale (ADAS-Cog13), ADCs iADL and mental state examination (MMSE) scores, did not change significantly (1). Most of the secondary endpoints, such as clinical dementia scale, Alzheimer's assessment scale, 13 item cognitive subscale, ADCs IADL and mental state examination scores, did not change significantly (1). This kind of research is obviously not exciting, the curative effect is not significant, some indicators are good and some are bad, did not let Aβ theory get rid of the shadow of failure. Obviously, the research on Alzheimer's disease cannot be limited to the thinking framework of treat the head when the head aches, treat the foot when the foot hurts. Like many chronic diseases, such as cardiovascular disease and diabetes, maybe aging is the underlying logic, and understanding the essence of aging is the solution.
Aging is a concept with rich connotation. It is not easy to face from biology, ethics to social governance, but it must be faced. From a biological point of view, the characteristics of aging include many aspects, including genomic instability, telomere shortening and loss, epigenetic changes, loss of protein synthesis and metabolic balance, imbalance of nutritional regulation, mitochondrial dysfunction, apoptosis, stem cell failure and changes in intercellular communication. The non-linear accumulation of cell damage in time and space is the essence of aging, which has unity in the seemingly opposite processes of tumor and aging. Building a model to describe aging may be a bigger and unrealistic idea than landing on Mars (2).
1, Mintun MA, et al. N Eng J Med. 2021;384:1691-1704.
2, Lopez-Otin C, et al. Cell. 2013;153:1194-1217.
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