Nat commun: recognizing the "time window" of brain cell death helps to treat Alzheimer's disease

February 15, 2020 / bioun / -- Alzheimer's disease is still the main cause of dementia in western society It is estimated that as many as 24 million people in the world suffer from this disease Alzheimer's disease is characterized by a gradual decline in cognitive ability, eventually affecting the basic functions of human activities, such as walking and swallowing At present, the exact cause of Alzheimer's disease is not clear, but the pathological changes of brain (including neuron loss and protein accumulation of β - amyloid plaque) are the diagnostic markers of Alzheimer's disease Mild cognitive impairment (MCI) describes mild but measurable changes in cognitive function, which are usually a precursor to Alzheimer's disease However, despite the importance of MCI, little is known about the changes that occur in the brain from MCI to Alzheimer's disease In a recent study published in the journal Nature communications, researchers led by the Tokyo Medical University and the University of dentistry now find that preventing pathological changes in the brain during the MCI phase can completely eliminate Alzheimer's disease "Neuronal death is very important in the development of Alzheimer's disease, but as we all know, it is very difficult to detect the dying cells in real time due to the inability to dye them with chemical or immunohistochemical methods," said Hikari Tanaka, the first author of the study Therefore, we used a new biomarker, pser46 MARCKS, to detect the degenerative neurites around dying neurons, so that we can quantify the level of necrosis in different disease stages " Surprisingly, the researchers found that neuron death occurred much earlier than previously thought, and the level of neuron necrosis in MCI patients was higher than that in mature Alzheimer's patients The researchers also observed a significant decrease in Yap protein levels in Alzheimer's disease model mice and in MCI human patients Yap can affect the activity of tead protein, the lack of which can lead to neuron necrosis After that, the gene therapy vector expressing Yap analogues was injected directly into the cerebrospinal fluid of Alzheimer's disease mouse model, which could prevent early neuron loss, restore cognitive function and prevent the deposition of β - amyloid plaques Timing of brain cell death uncovers a new target for Alzheimer's treatment