Objective： To constuct peroxisome proliferator-activated receptor γ coactivator-1 alpha (Pgc-1alpha) knockout mouse model in Alzheimer′s disease (AD)-related pathologic regions. Methods： Pgc-1alphafl/fl homozygous mice were obtained by crossing Pgc-1alphafl/+ heterozygous offspring. Pgc-1alphafl/fl homozygous mice were hybridized with Cre tool mice (Calb1-Cre), which specifically expressed Cre recombinase in AD lesion brain regions (cortex and hippocampus), and the genetic DNA of progeny transgenic mice was extracted and identified by PCR. The expression of PGC-1α protein in brain and kidney of transgenic mice and wild-type mice was detected by Western blotting. Results： Dual PCR analysis revealed that mice exhibiting simultaneous amplification of 400 bp and 444 bp bands were characterized by Pgc-1alpha deletion specific to AD-related brain regions (Pgc-1alphafl/fl::Calb1-Cre, Pgc-1alpha-/-). The results of Western blotting showed that the expression of PGC-1α protein in the brain region of conditioned knockout mice was significantly decreased compared with that of wild-type mice (P<0.05). Conclusion： Conditional Pgc-1alpha knockout mice in AD-related pathological brain regions were successfully constructed.

Objective： To explore the role of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) in improving Alzheimer′s disease (AD), as well as its potential mechanisms with a particulars focus on optic atrophy 1 (OPA1) regulation. Methods： In vitro, AD models were constructed by transfecting APPswe plasmids into N2A cells. qRT-PCR was used to evaluate the impact of mutAPP overexpression on the varies of PGC-1α and OPA1 transcription. APPswe and PGC-1α plasmids were cotransfected into N2A cells, regulation effect of PGC-1α on the levels of OPA1 transcription were evaluated by qRT-PCR during AD. In vivo, by infusing AAV-PGC1α into the lateral parietal association (LPtA) cortex of APP/PS1 brain, we successfully overexpressed  PGC-1α in the LPtA of APP/PS1 mouse. The regulatory effect of PGC1α on the expression of OPA1 and on the morphological changes of mitochondrial inner membrane during AD were examined by immunohistochemistry and transmission electron microscopy respectively. Results： Paralleling AD-like Aβ deposits, a significant reduction in the levels of PGC-1α and OPA1 was observed in APP/PS1 mice and APPswe transfected cells (all P<0.01). Furthermore, overexpression PGC-1a in LPtA rescued the mitochondrial damage, especially on damaged mitochondrial inner membrane in AD. Notably, upregulated expression of OPA1 were available in the LPtA cortex of APP/PS1 mice (all P<0.01) . Conclusion： PGC-1α contributes to the regulation of the mitochondrial fusion, thereby affecting Aβ aggregate in AD. Elevating of the PGC-1α level, either pharmacologically or through other means, could present a new therapeutic strategy for AD.
［Key words］Alzheimer′s disease; APP/PS1 mice; peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α); optic atrophy 1(OPA1); mitochondria; fusion protein

Objective： To investigate the correlation between serum lipoprotein（a）［Lp（a）］and Alzheimer′s disease（AD）.Methods： A retrospective casecontrol study was conducted on 103 AD patients>60 years old who were admitted to the Department of Neurology of Nanjing First Hospital from January 2015 to December 2018， and another 103 age and gendermatched healthy elderly subjects during the same period were selected as controls. Univariate and multivariate binary Logistic regression analysis and ROC curve were used to explore the correlation between serum Lp（a）level and the risk of AD. Furthermore， the effect of serum Lp（a） level on the risk of AD in different age groups was further investigated. Results： After the quinquepartite method of serum Lp（a） level， the first group（Q1）was used as a reference. With the increase of serum Lp（a） level， the risk of AD gradually decreased. The relative risks of groups Q2 to Q5 were 0.600， 0.471， 0.406 and 0.332（P for trend=0.011）， respectively. After adjusting for hypertension， diabetes， cardiovascular disease， serum creatinine， triglyceride， total cholesterol， highdensity lipoprotein cholesterol（HDLC）， glycosylated hemoglobin（HbA1c）， and lipoprotein associated phospholipase A2（LpPLA2）， Q1 was also used as a reference for estimating the relative risk of AD. The relative risks from Q2 to Q5 were 0.475， 0.343， 0.302 and 0.367（P for trend=0.020）， respectively. ROC curve analysis showed that the increase of serum Lp（a）level could reduce the risk of AD to a certain extent（AUC=0.601）， and it was not a good predictor. Taking lgLp（a） as the continuous variable， the increase of serum Lp（a） level was not correlated with the risk of AD in patients<75 years old（OR=1.082， P=0.769）， while the increase of serum Lp（a）level in patients≥75 years old was significantly correlated with the risk reduction of AD（OR=0.718， P=0.006）. Conclusion： There is a significant correlation between the increase of serum Lp（a）level in patients≥75 years old and the decrease of the risk of AD.

阿尔茨海默病（Alzheimer′s disease，AD）是由多致病因素引起的缓慢进展的、以认知障碍为特征的常见老年痴呆。脑内神经环路异常是其临床表型的核心基础，但临床尚无有效控制AD发展或逆转症状的治疗方法。因此，疾病的超早期识别和干预已成为AD领域的研究重点。基于目前神经环路领域研究进展，关键靶点的识别，使得导航定位系统支持下的重复经颅磁刺激治疗有望成为AD超早期精准干预的新技术。本文基于AD的神经环路基础和潜在靶向干预方式进行综述。

阿尔茨海默病（Alzheimer′s disease，AD）是最常见的老年性痴呆，西医将其定义为慢性退行性中枢神经系统疾病，已成为严重影响老年人群健康的重大疑难疾病。AD依症状属中医学的“呆病、善忘、健忘”等范畴。后世医家认为，痴呆病症的主要发病病机在于肾精气亏虚，髓海不足，脑不得充养而神智减退，同时，五脏输布无力，酿生痰浊，痰阻清窍，神智蒙昏。本文旨在从AD发病可能存在的机制方面，如毒性蛋白的形成、神经炎症、神经元丢失等，综述补肾、化痰类中药复方、单味药及其化学成分治疗AD的研究现状。

 阿尔茨海默病（Alzheimer′s disease, AD）是以渐进性减退和逐渐恶化的认知功能障碍为主要临床特征的神经退行性疾病，伴有全脑萎缩现象并有β淀粉样蛋白和tau蛋白出现。自噬是一种保守且溶酶体依赖的过程，在此过程中细胞器和多种蛋白被降解、回收并重新利用。自噬功能缺陷可能会导致AD患者脑区毒性蛋白聚集且不能降解。本文对自噬及其与AD相关的机制和调控基因进行阐述。

Objective: To analyse the changes of selfreferential network （SRN）and cerebrospinal fluid pathological markers amyloid β-protein （Aβ）, total tau （t-tau） and phosphorylated tau （p-tau） for patients with amnestic mild cognitive impairment（aMCI）. Methods: A total of 51 aMCI patients were enrolled in the study. According to the cognitive awareness index, they were divided into the aMCI group with impaired cognitive awareness（n=20）and the aMCI group（n=31）with cognitive awareness preserved. All patients underwent resting functional magnetic resonance （rsfMRI）, lumbar puncture, and cognitive assessment. Independent component analysis was used to extract SRN; two-sample t test was used to explore the functional connectivity of SRN and cerebrospinal fluid （Aβ, t-tau and p-tau）changes; Pearson correlation analysis was used to explore the relationship between cognitive awareness index and functional connectivity changes and the levels of cerebrospinal fluid Aβ, t-tau and p-tau. Results: The aMCI group with impaired cognitive awareness showed hyperconnectivity in the bilateral medial orbitofrontal cortex, left anterior cingulate gyrus and right rectus gyrus （AlphaSim correction, P<0.001, voxel number>17）. The difference in brain function connectivity between the two groups was negatively correlated with the cognitive awareness index（r=-0.457, P<0.000）. The level of Aβ in cerebrospinal fluid in the aMCI group with impaired cognitive awareness was significantly lower than that of the aMCI group with cognitive awareness preserved（P<0.01）, p-tau and t-tau in cerebrospinal fluid were significantly increased than those of the aMCI group with cognitive awareness preserved（P<0.001）. The cerebrospinal fluid Aβ level was positively correlated with cognitive awareness index（r=0.331, P=0.025）, and cerebrospinal fluid t-tau and p-tau levels were negatively correlated with cognitive consciousness index （r=-0.534,-0.508, both P<0.001）. Conclusion: SRN is the neuroimaging basis of cognitive awareness; aMCI patients with impaired cognitive awareness have impaired functional connectivity of SRN and more severe deposition of Alzheimer′s disease pathological markers.