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Objective:To analyze the modifiable risk factors for early-onset Alzheimer's disease (EOAD), and provide evidence for primary prevention of EOAD.Methods:Forty patients with EOAD, admitted to our hospital from January 2015 to April 2020, were selected as EOAD group, and 120 healthy controls accepted physical examination and matched with EOAD patients in age, gender and education level were selected. Demographic characteristics and clinical data of patients from the EOAD group and subjects from the control group were compared retrospectively, and multivariate Logistic regression was used to analyze the independent risk factors for onset of EOAD.Results:As compared with the control group, the EOAD group had significantly higher proportion of patients with hypertension, non-traumatic tooth loosening or loss, history of traumatic brain injury, hearing impairment, chronic stress and/or anxiety, and sleep disorder ( P<0.05). The results of multivariate Logistic regression analysis showed that hypertension ( OR=4.559, 95%CI=1.523-13.643, P=0.007), non-traumatic loss or loosing of tooth ( OR=5.345, 95%CI=1.989-14.346, P=0.001), hearing impairment ( OR=9.336, 95%CI=2.033-27.850, P=0.000), chronic stress and/or anxiety ( OR=7.375, 95%CI=2.612-20.822, P=0.000), and sleep disorder ( OR=4.875, 95%CI=1.520-15.625, P=0.002) were independent risk factors for onset of EOAD. Conclusion:Hypertension, non-traumatic loss or loosing of tooth, hearing impairment, chronic stress and/or anxiety, and sleep disorders are risk factors for onset of EOAD; the screening and intervention of these risk factors can be used as a primary prevention strategy for EOAD.
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Objective To observe the effects of histone deacetylases inhibitor (HDACi) on cognitive performance and cerebral tau phosphorylation in transgenic mice coexpressed five familial Alzheimer' s disease mutations (5XFAD).Method The total 12 5XFAD-CC and 12 wild type (WT) mice were administrated with suberoylanilide hydroxamic acid ( SAHA,n =7) and vehicle ( n =5 ),respectively.The cognitive performance was assessed by Y-maze and Morris water maze.The protein levels of acetylated α-tubulin,total tau and phosphorylated tau and phosphorylated glycogen synthase kinase-3β (GSK3β) were determined by Western blotting.Results SAHA ameliorated learning and memory deficits in 5XFAD-CC mice (39.10％ ±2.25％,t =2.688,P =0.0312 for total numbers of entrance in novel arm; 26.81％ ±0.78％,t =3.271,P =0.017 for time spending in novel arm; F =5.936,P =0.045 for hidden platform;31.70％ ±4.21％,t =2.317,P =0.049 for probe trial).Administration of SAHA significantly increased acetylated α-tubulin in hippocampus of WT and 5XFAD-CC mice (26.42％ and 29.64％,respectively).Additionally,SAHA attenuated tau-pSer396,tau-pSer404 and tau-pThrThr231 in hippocampus of 5XFAD-CC mice (24.22％,48.98％ and 26.95％,respectively). Moreover,hippocampal phosphorylated GSK3β was markedly reduced in SAHA-treated 5XFAD-CC mice (31.29％). Conclusion SAHA may improve cognitive performance in 5XFAD-CC mice, which is associated with its significant effects on the phosphorylation of tau and GSK3β.
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Objective To explore whether ginsenoside Rg1 can attenuate ?-amyloid peptide 25-35-induced Tau hyperphosporylation in rat embryo cortical neurons by regulating the activity of GSK-3? and PP2A. Methods Primary cultures of cortical neurons were prepared from the embryonic day 18?2 in Sprague-Dawley rats. The experimental groups were designed as follows:1.Neurons culture (control group); 2. Neurons exposed to 20?mol/L A?_ 25-35 for 12 hours (A?-model group); 3.Neurons exposed to 20?mol/L A?_ 25-35 and 10 mmol/L lithium chloride (LiCl), a specific inhibitor of glycogen synthase kinase-3?(GSK-3?), for 12 hours (LiCl group); 4.Neurons exposed to 20?mol/L A?_ 25-35 for 12 hours in the presence of 24-hour pretreatment with ginsenoside Rg1 (Rg1 pretreatment group) . Western blotting and immunocytochemical staining were used to detect the levels of Tau phosphorylation,total Tau and GSK-3? in cortical neurons. Non-radioimmunoassay was introduced to detect the activity of protein phosphatase 2A (PP2A). Results In A?-model group, the levels of Tau protein phosphorylation in the sites of Ser 396 ,Ser 199/202 ,Thr 231 and total Tau were enhanced. Meanwhile, the expression of GSK-3? was also increased, but the activity of PP2A was unchanged. In LiCl group and Rg1 pretreatment group , the hyperposphorylations of Tau protein and total Tau and the expression of GSK-3? were markedly reduced compared to those of the A?-model group (P