Stocktaking: Holiday Charging, Summary of Recent Important Research Progress on Alzheimer's Disease

The Alzheimer's dangerous gene APOE4 destroys the blood-brain barrierhttps://news.medsci.cn/article/show_article.do?id=c3b319325994lipoprotein E (APOE4) e4 variant is the main susceptibility to Alzheimer's disease, which can lead to accelerated decomposition of BBB and degeneration of cells around the cerebral capillaries, while cells around the cerebral capillaries can maintain the integrity of BBBHowever, it is not clear whether the cerebrovascular effect of APOE4 causes cognitive dysfunctionRecently, researchers have found that, unlike individuals without APOE4 (?3/?3), there is damage to the BBB of the individual hippocampus and the inner temporal lobe, which carries aThis phenomenon is evident in carriers of APOE4 whose cognitive function is not impaired, and becomes more severe in carriers with cognitive impairment, and is not associated with amyloid-beta or tau lesionsIn APOE4 carriers, high baseline levels of BBB endomecell damage biomarkers in cerebrospinal fluid, soluble PDGFR beta, can predict future cognitive decline, even after controlling amyloid-beta and tau states, which is associated with increased activity in the cerebrospinal fluid bBB-degraded cyclic protein A-matrix metalloproteinase-9 pathway 19Therefore, the results show that bBB damage is involved in APOE4-related cognitive decline and is independent of Alzheimer's pathology, which may be a potential therapeutic target for APOE4 carriersAPOE2 reduces the risk of Alzheimer's diseasehttps://news.medsci.cn/article/show_article.do?id=30771926e850existing studies have shown that every additional copy of the lipoprotein E4 (APOE4) allele is associated with an increased risk of Alzheimer's disease, while the APOE2 alleles are associated with a lower risk of Alzheimer's diseaseBut so far, it is not clear whether APOE2 pure-combination genetics have a particularly low riskAs a result, researchers recently studied the likelihood of Alzheimer's disease and other aspects in more than 5,000 cases and controls of Alzheimer's disease with clinical and neuropathological characteristicsThe results showed that the APOE2/2 genotype had a lower risk of developing Alzheimer's disease than APOE2/3 and 3/3The APOE2/2 genotype is particularly less likely to develop Alzheimer's disease than APOE4/4In the neuropathologically confirmed groups, the effects of the dose slots of aPOE2 and APOE4 gene were significantly greater than those of more than 24,000 cases of neuropathic unconfirmed cases and control groupsOverall, the results suggest that finding and targeting APOE and its variants to influence Alzheimer's disease may have a significant impact on understanding, treating and preventing Alzheimer's disease3, tau protein sistoses mainly through LRP1
https://news.medsci.cn/article/show_article.do?id=27dc19136285the spread of protein aggregates is a common feature of many neurodegenerative diseases during the progression of diseaseMicrotubule-related protein tau plays a central role in the pathogenesis of several forms of dementia, known as tauopathies: including Alzheimer's disease, prehypertension dementia and chronic traumatic encephalopathyAlthough Tau's propagation has been widely studied, we still don't know much about its basic cellular mechanismsRecent lypoprotein receptor-related protein 1 (LRP1) controls the internal swallowing of tau and its subsequent propagation, according to recent resultsThe knock-out of LRP1 significantly reduced the intake of tau in H4 glioma cells and induced pluripotent stem cells (iPSC) derived neuronsThe interaction between Tau and LRP1 is mediated by lysine residues in the tau microtube binding repeat ingressIn addition, in the model of tau propagation in mice in the body, the downward adjustment of LRP1 was found to effectively reduce tau propagation between neuronsTherefore, the results show that LRP1 is a key regulator in the brain for tau transmission and is therefore a potential target for the treatment of diseases involving tau transmission and aggregationAnalysis of the risk of using hormones to treat Alzheimer's disease in women after menopause
https://news.medsci.cn/article/show_article.do?id=d7171642389cstudy was designed to compare the risk of using hormones in finnish postmenopausal women with Alzheimer's disease or without Alzheimer's diseaseThe researchers collected data from Finland's national population and drug register for the period 1999-2013 The 84,739 women with menopausal alzheimer's disease were also matched by 84,739 healthy menopausal women, and data on hormone therapy use came from Finland's National Drug Reimbursement Registry The results showed that of 83,688 (98.8%) women, the age of diagnosis of Alzheimer's disease was 60 years of age or older, and 47,239 (55.7%) were over 80 years of age at the time of diagnosis The use of systemic hormone therapy increases the risk of Alzheimer's disease by 9-17% The increased risk of estrogen-progesterone therapy users was not associated with different progesterone (acetylene acetate, methylprogesterone acetate or other progesterone), but in women who were younger than 60 at the beginning of hormone therapy, these increased risks were associated with 10 years of exposure to hormone therapy In addition, the age at which systemic hormone therapy begins is not a decisive factor in the increased risk of Alzheimer's disease It is shown that long-term use of systemic hormone therapy may increase the overall risk of Alzheimer's disease, regardless of the type of progesterone or the age at the beginning of systemic hormone therapy Alzheimer's-related protein is the basis of cognitive impairment in type 1 diabetes
https://news.medsci.cn/article/show_article.do?id=0ea516148117 diabetes (DM) is one of the most devastating diseases affecting the aging of the population Recent evidence suggests that DM is a risk factor for many brain diseases because of its direct impact on cognition New findings suggest that microtubule-related protein tau is pathologically modified in Patients with DM However, it is not clear whether pathological tau modification plays a central role in dM-related cognitive defects To solve this problem, the researchers used functional acquisition and loss of function to regulate tau levels in mouse models of type 1 diabetes (T1DM) and type 2 diabetes (T2DM) The study shows that tau differentially contributes to DM-induced cognitive and synaptic defects On the one hand, over-expressing wild human tau further aggravates t1DM-induced cognitive and synaptic damage, as under T1DM conditions, human tau-treated mice exhibit strong defects in learning and memory On the other hand, the decrease and increase of tau levels did not affect the cognition of T2DM mice In summary, these results provide new highlights for the different molecular mechanisms of cognition and synaptic damage associated with T1DM and T2DM Source: MedSci Original