Recommendation for and comparison of three types of dementia： Alzheimer’s disease, subcortical ischemic vascular dementia, and mixed dementia

With the progress in global demography of aging, dementia has become a great world health-care issue that require urgent attention and settlement. Demen-tia can arise from a variety of factors, such as neuronal degeneration for Alzheimer’s disease （AD）, vascular risk factors and multiple infarcts for vascular dementia （VaD）, and both degeneration and vascular factors for mixed de-mentia （MD）. Pathophysiology of AD includes the amy-loid and tau protein hypothesis, and infammation-related mechanisms are also widespread mentioned. Subcortical ischemic vascular dementia （SIVD）, a subtype of VaD, is commonly caused by complete or incomplete lacunar infarction of VaD pathology. MD involves both degenera-tion and vascular factors, and the interaction between the two results in the complication of the pathological mech-anism and clinical phenotype. The clinical manifestationsof AD are often divided into four stages according to the progress of the disease, while the phenotypes of SIVD usually has two categories. As for MD, the phenotypes are complex and diverse. Several clinical studies showedthat its symptoms and signs are more similar to SIVD than AD. This article aims to analyze and compare the differ-ent aspects of the three kinds of dementia.

Perspectives on a collaborative Canada-China research program on diagnostic biomarkers for pre-dementia stages of Alzheimer’s disease

As biomarkers are important in the early diagnosis ofAlzheimer’s disease （AD）, the frst collab-orative work of recruiting early-onset familial AD （EO-FAD） families in Canada and China was initiated in 2012. The registration networks have collected hundreds of pedigrees, for which genetic screening, neuropsycholog-ical tests and amyloid and tau imaging was used to study diagnostic biomarkers for preclinical and mild cognitive impairment （MCI） stages of AD. Besides identifying ped-igrees with novel mutations in presenilins （PSENs）/amy-loid precursor protein （APP）, the program has benefted training of Chinese research fellows, AD clinical trials forprevention,the ethical concernsfor clinical fndings, and other collaborative projects with Chinese investiga-tors. Further research of the collaborative program may facilitate the testing and clinical use of novel treatments for EOFAD and late onset AD and contribute to dementia prevention strategies in Canada and China.

Hypertension and Alzheimer’s disease

Alzheimer’s disease （AD） accounts for 60% to 80% of dementia cases and is the most common cause of dementia. In the past decade, studies have shown a close association between blood pressure and AD. It is found that elevated blood pressure at midlife would in-crease the risk of dementia, including AD. However, there is nodefnitive conclusion about the relationship between elderly blood pressure and cognitive function. Abnormal pulse pressure may also increase the risk of dementia. The impact of antihypertensive drugs is inconclusive, and the mechanism of their protection of cognitive function is not clear.

Disrupted functional connectivity of default mode network and executive control network in patients with vascular cognitive impairment, no dementia

Objective： To investigate functional connectivity within default mode network （DMN） and ex-ecutive control network （ECN） in vascular cognitive im-pairment, no dementia （VCIND）. Methods： Twenty-eight VCIND patients and sixteen healthy controls were recruit-ed. A seed-based connectivity analysis was performed us-ing data from resting-state functional magnetic resonance imaging （fMRI）. Based on previous fndings, posteriorcingulate cortex （PCC） and dorsolateral prefrontal cortex （DLPFC） were chosen as regions of interest to study these networks.One-sample t-test and two-sample t-test were used for statistical analysis. Results： Compared with thecontrols, the VCIND group exhibited increased functional activity in such DMN regions as the left inferior temporal gyrus, parahippocampal gyrus, and medial frontal gyrus. The VCIND group had decreased functional connectivity of DMN at right superior frontal gyrus, left mid-cingu-late area, the medial part of left superior frontal gyrus, and bilateral medial frontal gyrus. The VCIND group also showed decreased functional connectivity of ECN pri-marilyat left inferior parietal gyrus, right angular gyrus, right middle occipital gyrus, and right middle frontal cor-tex. Conclusions： Increased functional connectivity with-in DMN and decreased functional connectivity within ECN suggested dysfunction of these two networks, which mightbe associated with the cognitive defcitsin patients with VCIND. These fndingsmay help usunderstandthe pathogenesis and clinical characteristics of VCIND.

Homocysteine and Alzheimer’s disease： a literature review

Increasing evidence in recent years sug-gests homocysteine （Hcy） is involved in the pathogene-sis of Alzheimer’s disease （AD）, and that modifying this risk factor may be an alternative approach to delaying or preventing onset of this disease. However, intervention studies uggest inconsistent effects of folic acid supple-mentation, with or without vitamin B12, on the prevention of incident AD. Studies with Hcy-lowering therapy show benefcial effects of B vitamins inpatients with mild cog-nitive impairment （MCI）, especially in those with high Hcy levels. Further studies are needed to confrm elevated Hcy levels as a potentially treatable risk factor for AD.

Effcacy and pharmacogenomics of donepezil

With the aging of society, dementia has become a more and more serious social problem. Alzhei-mer’s disease （AD） is a major cause of dementia, and there is no drug to reverse the disease progression. Donepezil is the main drug currently in symptomatic treatment. How-ever,the effcacy of donepezil was moderate, with the patient variably responding to the treatment with donepe-zil. The commonest adverse events in the treatment were nausea,vomiting,and diarrhea; QT prolongation rarely occurred. Many patients gave up treatment because of adverseevents orlack of effcacy. Pharmacogenomicsis developed on the basis of pharmacogenetics, by studying the polymorphisms in genes involved in drug metabolicenzymes, transporter and drug receptor, to guide individ-ualized treatment. In terms of the pharmacogenomics on the effcacyof onepezil, there is no clear conclusion ex-cept CYP2D6 genotype affecting drug clearance.

An Overview of Genome-Wide Association Studies in Alzheimer＇s Disease

Genome-wide association studies（GWASs）have revealed a plethora of putative susceptibility genes for Alzheimer＇s disease（AD）. With the sole exception of the APOE gene, these AD susceptibility genes have not been unequivocally validated in independent studies. No single novel functional risk genetic variant has been identified. In this review, we evaluate recent GWASs of AD, and discuss their significance, limitations, and challenges in the investigation of the genetic spectrum of AD.

Impaired Autophagy in Hilar Mossy Cells of the Dentate Gyrus and Its Implication in Schizophrenia

Schizophrenia （SCZ） is a complex disease that has been regarded as a neurodevelopmental, synaptic or epigenetic disorder. Here we provide evidence that neurodegeneration is implicated in SCZ. The DTNBP1 （dystrobrevin-binding protein 1） gene encodes dysbindin-1 and is a leading susceptibility gene of SCZ. We previously reported that the dysbindin-lC isoform regulates the survival of the hilar glutamatergic mossy cells in the dentate gyms, which controls the adult hippocampal neurogenesis. However, the underlying mechanism of hilar mossy cell loss in the dysbindin-l-deficient sandy （sdy） mice （a mouse model of SCZ） is unknown. In this study, we did not observe the apoptotic signals in the hilar mossy cells of the sdy mice by using the TUNEL assay and immunostaining of cleaved caspase-3 or necdin, a dysbindin-1- and p53-interacting protein required for neuronal survival. However, we found that the steady-state level of LC3- II, a marker of autophagosomes, was decreased in the hippocampal formation in the mice lacking dysbindin-lC. Furthermore, we observed a significant reduction of the cytosolic LC3-II puncta in the mossy cells of sdy mice. In addition, overexpression of dysbindin- 1C, but not 1A, in cultured cells increased LC3-II level and the LC3 puncta in the transfected cells. These results suggest that dysbindin- 1C deficiency causes impaired autophagy, which is likely implicated in the pathogenesis of SCZ.

Web Resources for Stem Cell Research

In this short review, we have presented a brief overview on major web resources relevant to stem cell research. To facilitate more efficient use of these resources, we have provided a preliminary rating based on our own user experience of the overall quality for each resource. We plan to update the information on an annual basis.

GSA:Genome Sequence Archive

With the rapid development of sequencing technologies towards higher throughput and lower cost, sequence data are generated at an unprecedentedly explosive rate. To provide an efficient and easy-to-use platform for managing huge sequence data, here we present Genome Sequence Archive （GSA; http：//bigd.big.ac.cn/gsa or http：//gsa.big.ac.cn）, a data repository for archiving raw sequence data. In compliance with data standards and structures of the International Nucleotide Sequence Database Collaboration （INSDC）, GSA adopts four data objects （BioProject, BioSample, Experiment, and Run） for data organization, accepts raw sequence reads produced by a variety of sequencing platforms, stores both sequence reads and metadata submitted from all over the world, and makes all these data publicly available to worldwide scientific communities. In the era of big data, GSA is not only an important complement to existing INSDC members by alleviating the increasing burdens of handling sequence data deluge, but also takes the significant responsibility for global big data archive and provides free unrestricted access to all publicly available data in support of research activities throughout the world.