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      Towards Personalized Intervention for Alzheimer’s Disease

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          Abstract

          Alzheimer’s disease (AD) remains to be a grand challenge for the international community despite over a century of exploration. A key factor likely accounting for such a situation is the vast heterogeneity in the disease etiology, which involves very complex and divergent pathways. Therefore, intervention strategies shall be tailored for subgroups of AD patients. Both demographic and in-depth information is needed for patient stratification. The demographic information includes primarily APOE genotype, age, gender, education, environmental exposure, life style, and medical history, whereas in-depth information stems from genome sequencing, brain imaging, peripheral biomarkers, and even functional assays on neurons derived from patient-specific induced pluripotent cells (iPSCs). Comprehensive information collection, better understanding of the disease mechanisms, and diversified strategies of drug development would help with more effective intervention in the foreseeable future.

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          Most cited references65

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          ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models.

          Alzheimer's disease (AD) is associated with impaired clearance of β-amyloid (Aβ) from the brain, a process normally facilitated by apolipoprotein E (apoE). ApoE expression is transcriptionally induced through the action of the nuclear receptors peroxisome proliferator-activated receptor gamma and liver X receptors in coordination with retinoid X receptors (RXRs). Oral administration of the RXR agonist bexarotene to a mouse model of AD resulted in enhanced clearance of soluble Aβ within hours in an apoE-dependent manner. Aβ plaque area was reduced more than 50% within just 72 hours. Furthermore, bexarotene stimulated the rapid reversal of cognitive, social, and olfactory deficits and improved neural circuit function. Thus, RXR activation stimulates physiological Aβ clearance mechanisms, resulting in the rapid reversal of a broad range of Aβ-induced deficits.
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            Association of mediterranean diet with mild cognitive impairment and Alzheimer's disease: a systematic review and meta-analysis.

            To conduct a systematic review of all studies to determine whether there is an association between the Mediterranean diet (MeDi) and cognitive impairment. We conducted a comprehensive search of the major databases and hand-searched proceedings of major neurology, psychiatry, and dementia conferences through November 2012. Prospective cohort studies examining the MeDi with longitudinal follow-up of at least 1 year and reporting cognitive outcomes (mild cognitive impairment [MCI] or Alzheimer's disease [AD]) were included. The effect size was estimated as hazard-ratio (HR) with 95% confidence intervals (CIs) using the random-effects model. Heterogeneity was assessed using Cochran's Q-test and I2-statistic. Out of the 664 studies screened, five studies met eligibility criteria. Higher adherence to the MeDi was associated with reduced risk of MCI and AD. The subjects in the highest MeDi tertile had 33% less risk (adjusted HR = 0.67; 95% CI, 0.55-0.81; p < 0.0001) of cognitive impairment (MCI or AD) as compared to the lowest MeDi score tertile. Among cognitively normal individuals, higher adherence to the MeDi was associated with a reduced risk of MCI (HR = 0.73; 95% CI, 0.56-0.96; p = 0.02) and AD (HR = 0.64; 95% CI, 0.46-0.89; p = 0.007). There was no significant heterogeneity in the analyses. While the overall number of studies is small, pooled results suggest that a higher adherence to the MeDi is associated with a reduced risk of developing MCI and AD, and a reduced risk of progressing from MCI to AD. Further prospective-cohort studies with longer follow-up and randomized controlled trials are warranted to consolidate the evidence. Systematic review registration number: PROSPERO 2013: CRD42013003868.
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              Wireless magnetothermal deep brain stimulation.

              Wireless deep brain stimulation of well-defined neuronal populations could facilitate the study of intact brain circuits and the treatment of neurological disorders. Here, we demonstrate minimally invasive and remote neural excitation through the activation of the heat-sensitive capsaicin receptor TRPV1 by magnetic nanoparticles. When exposed to alternating magnetic fields, the nanoparticles dissipate heat generated by hysteresis, triggering widespread and reversible firing of TRPV1(+) neurons. Wireless magnetothermal stimulation in the ventral tegmental area of mice evoked excitation in subpopulations of neurons in the targeted brain region and in structures receiving excitatory projections. The nanoparticles persisted in the brain for over a month, allowing for chronic stimulation without the need for implants and connectors.
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                Author and article information

                Contributors
                Journal
                Genomics Proteomics Bioinformatics
                Genomics Proteomics Bioinformatics
                Genomics, Proteomics & Bioinformatics
                Elsevier
                1672-0229
                2210-3244
                28 September 2016
                October 2016
                28 September 2016
                : 14
                : 5
                : 289-297
                Affiliations
                [1 ]CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
                [2 ]Cunji Medical School, University of Chinese Academy of Sciences, Beijing 100049, China
                [3 ]Center of Alzheimer’s Disease, Beijing Institute for Brain Disorders, Beijing 100053, China
                Author notes
                [* ]Corresponding author. leihx@ 123456big.ac.cn
                [a]

                ORCID: 0000-0002-3645-8115.

                [b]

                ORCID: 0000-0002-5675-1036.

                [c]

                ORCID: 0000-0002-9808-1173.

                [d]

                ORCID: 0000-0002-4622-1904.

                [e]

                ORCID: 0000-0003-0848-8349.

                [f]

                ORCID: 0000-0001-7071-666X.

                [g]

                ORCID: 0000-0001-9277-2507.

                [h]

                ORCID: 0000-0003-0496-0386.

                Article
                S1672-0229(16)30138-3
                10.1016/j.gpb.2016.01.006
                5093853
                27693548
                a7ef3340-13cd-41ba-9553-125998e65ead
                © 2016 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 18 December 2015
                : 14 January 2016
                : 31 January 2016
                Categories
                Review

                alzheimer’s disease,demographic information,genome,peripheral biomarkers,ipsc technology

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