The credit for first time describing a dementing condition, which later became known as Alzheimer’s disease, goes to German physiatrist and neuropathologist Dr. Alois Alzheimer.Alzheimer disease (AD) an aggressive form of dementia, manifesting in memory, language and behavioral deficits [1,2]. According to the World Health Organization (WHO) estimates, the over all projected prevalence in global population will quadruple in the next decades, reaching 114 million patients by 2050 [3]. Apart from having a great social impact, this would clearly lead to increased economic burden to healthcare systems worldwide [4,5]. It is currently estimated that 46.8 million people worldwide have dementia with an estimated global cost of dementia care at US$818 billion in 2010 [6]. By 2030 it is estimated that there will be 74.7 million people with dementia, and the cost of caring for these individuals could rise to some US$2 trillion. There are no effective options available at present for prevention and treatment of Alzheimer disease despite all scientific reports. Alzheimer’s disease progresses gradually and can last for decades. There are three main stages of the disease, each with its own challenges and symptoms. By identifying the current stage of the disease, physicians can predict what symptoms can be expected in the future and possible courses of treatment. Each case of AD presents with a unique set of symptoms, varying in severity. Inheritance of certain genes is a risk factor for AD, with both familial and sporadic cases occurring. In sporadic AD, which is the more common form, there is a link with the apolipoprotein 4 (APOE4) allele, with the risk being greater in homozygotic situations [7,8]. Environmental factors, vascular factors and psychical factors contribute to the development of Alzheimer’s disease. Currently, no drugs are available to halt the progression of neurodegeneration in Alzheimer disease; the nature of Alzheimer’s disease treatment is symptomatic [9]. For instance, cholinesterase inhibitors (CIs) that promote cholinergic neurotransmission are used in mild to moderate cases of Alzheimer’s disease. Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is used in moderate to severe cases to prevent excitotoxicity, and antipsychotics and antidepressants are used in the treatment of neuropsychiatric symptoms [10,11]. Right now, there’s no proven way to prevent Alzheimer’s disease. Research into prevention strategies is on going and is getting developed day by day. The strongest evidence so far suggests that you may be able to lower your risk of Alzheimer’s disease by decreasing your risk of heart disease. Many of the same factors that tend to increase your risk of heart disease can also increase your risk of Alzheimer’s disease and vascular dementia. Important factors that may be involved include high blood pressure, high blood cholesterol, excess weight and diabetes. Alzheimer’s disease is complex, and it is unlikely that any one drug or other intervention can successfully lead to its proper treatment. Current approaches focus on helping people maintain mental function, manage behavioral symptoms, and slow or delay the symptoms of disease. Researchers hope to develop therapies targeting specific genetic, molecular, and cellular mechanisms so that the actual underlying cause of the disease can be stopped or prevented.

      The future of treatment of Alzheimer’s disease lies in the targeting of neuritic plaques (NPs) and neurofibrillary tangles (NFTs), which have the potential to delay neurodegeneration [12]. This review article will provide brief knowledge to Alzheimer’s disease and its diagnosis and causes. This article selectively reviews some of the highlights and emerging trends in Alzheimer disease treatments.

Clinical Features

      Rice is extremely vulnerable to low temperature, especially at the seedling stage. Therefore, it is practical to enhance the tolerant level of rice at this stage. TIFY1b, a transcription factor, is one of the cold tolerant involving genes discovered in rice (Huang et al., 2017). CRISPR/Cas9 was employed to edit this gene and its homology gene in Nipponbare rice. The results showed that the highest mutagenesis frequency was more than 85% in T0 transgenic lines. The mutation principally occurred in insertion and deletion of one nucleotide. CRISPR/Cas9 changed the DNA sequences at targeted sites and also affected the function of those genes through protein analysis. With CRISPR/Cas9 technique, the study successfully generated a variety of TIFY1 mutant lines in rice.

Rice blast disease resistance

      Blast is considered one of the highly severe diseases affecting the sustainable production of rice, especially causing dramatic yield losses. Many experimentations have been conducted to produce and develop high yield and resistant rice cultivars to the disease using a variety of molecular biological techniques (Yan et al., 2017).The CRISPR/Cas9 method initially obtained some encouraging achievements. In particular, the rice blast resistance was improved in the Kuiku131 rice variety after editing the target gene OsERF922 involving in the resistant ability (Liu et al., 2012). The knockout OsERF922 gene results in T0 generation showed that the highest frequency of mutant individuals was induced by C-ERF922S1S2S3 with ninety percents of recovery, following by C-ERF922S1S2 and C-ERF922 with 70 and 42% (Wang et al., 2016). Interestingly, the blast resistance of T2 generation was considerably improved by the mutation at the two stages consisting of seedling and tillering. The finding suggested that CRISPR/Cas9 is an effective technique for improving rice blast resistance.

Herbicide resistance

      The main advantage of the development of the herbicide resistance biotechnology in rice has significantly benefited the management and application of agrochemicals, which have been initiated due to the complex regulatory process and public health (Li and Jennings, 2017a, b). Since human and environmental health are heavily impacted by the use of agrochemicals (Li, 2018), herbicide resistance biotechnology of rice is one of the most effective ways to manage its application.

      Rice has been developed the herbicide resistance to retain the growth under treatments of a range of herbicides. The Acetolactate Synthase 1 (ALS1) is one of the core enzymes involving herbicide resistance of rice. Sun et al., (2016) carried out mutations using multiple discrete points in the gene ALS of rice under applying CRISPR/Cas9 technique. They used two gRNAs for guiding the system to change both amino acid residues including W584 to L and S627 to I. The obtained results showed that CRISPR/ Cas9-mediated homology-directed repair was successful. This indicated that the method could create doublestranded breaks at the targeted sites where CRISPR/Cas9 aimed to edit. Additionally, herbicide resistance tests were in line with the mentioned results in which the mutant plants were resistant to bispyribac sodium (100 µM) after 10 days of the foliar application while the non-edited plants died after treatment of the herbicide at the same concentration.

      Another experiment was conducted on the rice Bentazon Sensitive Lethal gene (BEL) that relates to bentazon and sulfonylurea herbicide resistance (Xu et al., 2014). The authors targeted the second exon of the BEL gene region of Nipponbare rice cultivar. The sequencing results indicated the effectiveness of sgRNA: Cas in rice with fifteen deletion and replacement mutations detected. The phenotypic screening supported the results of genetic mutants. Once again, the CRISPR/Cas9 was conclusively proved to be potential in editing rice genes.

Others

      The CRISPR/Cas9 technique has also been proved to capablyedit other genes in rice. Ten target genes including OsPDS (albino), OsPMS3 (photo-period sensitive male sterile), OsMYB5 (MYB family transcription factor), OsEPSPS (lethal), OsYSA (albino young seedling), OsMSH1 (pleotrophic phenotype), OsROC5 (abaxial leaf rolling), OsDERF1 (drought tolerance), OsSPP (early seedling leaf chlorosis), and OsMYB1 (MYB family transcription factor) were selected for a gene-editing experiment in the study of Zhang et al., (2014). The results showed that the mutation rates ranged from 21.1 to 66.7% in T0 plants. Five target sites with more than 50% of mutants consisted of OsMYB1, OsYSA (sgRNA1), OsROC5, OsYSA (sgRNA2), and OsDERF1. Additionally, the mutants were successfully inherited to the T1 generation according to the Mendelian law. Briefly, CRISPR/Cas9 system was demonstrated to have potential in editing rice genome.

      Five years of invention, CRISPR/Cas has been experimentally tested in plenty of genes of many living cells, and most of the trials obtained encouraging results. Among important crops, rice is regarded the most crucial crop because of its high percentage of consumption worldwide. To adapt to climate change, the essential genes relating to abiotic and biotic stress resistance such as cold tolerance, blast disease resistance and herbicide resistance have been targeted for editing using CRISPR/Cas system to generate novel strong, high-yield and quality rice varieties for sustainable production. As a result, transgenic rice with desirable traits can be expected to produce in the near future by application of CRISPR/Cas technology.