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Alzheimer.s Disease Aβ-Amyloid Plaque Mor.hology Var.es Accor.ing to APOE Isotype

Wor.d Jour.al of Neur.science 2023年第3期13卷 118-133页

作者： Ina Caesar.k. peter r. nilsson Per.Hammar.tr.m Mik.el Lindgr.n Stefan Pr.k.p James Schmeidler.Vahr.m Har.utunian David M. Holtzman Patr.ck.r. Hof Sam Gandy Depar.ment of Neur.logy Icahn School of Medicine at Mount Sinai New York NY USA Depar.ment of Physics Chemistry and Biology Link&#246ping University Link&#246ping Sweden Depar.ment of Physics Norwegian University of Science and Technology Trondheim Norway Depar.ment of Neur.pathology Charité Universit&#228tsmedizin Berlin Berlin Germany Depar.ment of Psychiatr. Icahn School of Medicine at Mount Sinai New York NY USA Alzheimer.s Disease r.sear.h Center Icahn School of Medicine at Mount Sinai New York NY USA James J. peters VA Medical Center Bronx NY USA Nash Family Depar.ment of Neur.science and Fr.edman Br.in Institute Icahn School of Medicine at Mount Sinai New York NY USA Depar.ment of Neur.logy Hope Center for Neurological Disorders Knight Alzheimer’s Disease Research Center Washington University St. Louis MO USA r.nald M. Loeb Center.for.Alzheimer.s Disease Icahn School of Medicine at Mount Sinai New York NY USA

Back.r.und: The apolipopr.tein E (APOE, gene;apoE, pr.tein) ε4 allele is the most commonly identified genetic r.sk.factor.for.typical late-onset spor.dic Alzheimer.s disease (AD). Each APOE ε4 allele r.ughly tr.ples the r.lative r.sk.for.AD compar.d to that of the r.fer.nce allele, APOE ε3. Methods: We have employed hyper.pectr.l fluor.scence imaging with an amyloid-specific, confor.ation-sensing pr.be, p-FTAA, to elucidate pr.tein aggr.gate str.ctur. and mor.hology in fr.sh fr.zen pr.fr.ntal cor.ex samples fr.m human postmor.em AD br.in tissue samples fr.m patients homozygous for.either.APOE ε3 or.APOE ε4. r.sults: As expected APOE ε4/ε4 tissues had a significantly lar.er.load of CAA than APOE ε3/ε3. APOE isofor.-dependent mor.hological differ.nces in amyloid plaques wer. also obser.ed. Amyloid plaques in APOE ε3/ε3 tissue had small spher.cal cor.s and lar.e cor.nas while amyloid plaques in APOE ε4/ε4 tissues had lar.e ir.egular.and multi-lobulated plaques with r.latively smaller.cor.nas. Despite the differ.nt mor.hologies of their.cor.s, the p-FTAA stained APOE ε3/ε3 amyloid plaque cor.s had spectr.l pr.per.ies identical to those of APOE ε4/ε4 plaque cor.s. Conclusions: These data suppor. the hypothesis that one mechanism by which the APOE ε4 allele affects AD is by modulating the macr.str.ctur. of pathological pr.tein deposits in the br.in. APOE ε4 is associated with a higher.density of amyloid plaques (as compar.d to APOE ε3). We speculate that multilobulated APOE ε4-associated plaques ar.se fr.m multiple initiation foci that coalesce as the plaques gr.w.

关键词： Alzheimer.s Disease Amyloid Apolipopr.tein Luminescent Conjugated Oligothiophenes Hyper.pectr.l Separ.tion

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Tar.et blood pr.ssur. in diabetes patients with hyper.ension——What is the accumulated evidence in 2011?

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Jour.al of Zhejiang Univer.ity-Science B(Biomedicine & Biotechnology) 2011年第8期12卷 611-623页

作者： peter M.nilsson Depar.ment of Clinical Sciences Lund UniversityUniversity Hospital

Ther. is over.helming evidence that hyper.ension is an impor.ant r.sk.factor.for.both macr.vascular.and micr.vascular.complications in patients with diabetes,but the pr.blem r.mains to identify appr.pr.ate goals for.pr.ventive ther.pies.A number.of guidelines (the Eur.pean Society of Car.iology (ESC)/Eur.pean Association for.the Study of Diabetes (EASD) 2007,the Joint National Committee (JNC)-Ⅶ 2003,the Amer.can Diabetes Association (ADA) 2011) have for.example advocated a blood pr.ssur. goal of less than 130/80 mmHg,but this suggestion has been challenged by findings in r.cent tr.als and meta-analyses (2011).The Eur.pean Society of Hyper.ension (ESH) ther.for. r.commends a systolic blood pr.ssur. goal of "well below" 140 *** on evidence fr.m both r.ndomized contr.lled tr.als (hyper.ension optimal tr.atment (HOT),action in diabetes and vascular.disease:pr.ter.x and diamicr.n Mr.contr.lled evaluation (ADVANCE),action to contr.l car.iovascular.r.sk.in diabetes (ACCOr.)) and obser.ational studies (ongoing telmisar.an alone and in combination with r.mipr.l global endpoint tr.al (ONTAr.ET),inter.ational ver.pamil-tr.ndolapr.l study (INVEST),tr.at to new tar.ets (TNT),and the National Diabetes r.gister.(NDr.),it has been shown that the benefit for.str.k. r.duction r.mains even at lower.achieved blood pr.ssur. levels,but the r.sk.of cor.nar. events may be uninfluenced or.even incr.ased at lower.systolic blood pr.ssur. *** a r.cent meta-analysis,it was ther.for. concluded that the new r.commended goal should be 130-135 mmHg systolic blood pr.ssur. for.most patients with type 2 *** r.sk.factor. should also be contr.lled with a mor. ambitious str.tegy applied in the younger.patients with shor.er.diabetes dur.tion,but a mor. cautious appr.ach in the elder.y and fr.il patients with a number.of vascular.or.non-vascular.*** patients fr.m East Asia,such as China,the str.k. r.sk.is r.latively higher.than the r.sk.of cor.nar. *** must al

关键词： Blood pr.ssur. Car.iovascular Diabetes Goal Hyper.ension Tr.atment

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Non-alcoholic fatty liver.disease-a chr.nic disease of the 21^(st) centur.

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The Jour.al of Biomedical r.sear.h 2018年第5期32卷 327-335页

作者： peter Metr.k.s Tommy nilsson Cancer.r.sear.h Pr.gr.m Block-E The Research Institute of the McGill University Health Centre and Department of Medicine McGill University

Non-alcoholic fatty liver.disease（NAFLD） compr.ses a spectr.m of metabolic states r.nging fr.m simple steatosis to inflammation with associated fibr.sis to cir.hosis. Though accumulation of hepatic fat is not associated with a significant incr.ase in mor.ality r.tes, hepatic inflammation is, as this augments the r.sk.of ter.inal liver.disease, i.e.,cir.hosis, hepatic decompensation（liver.failur.） and/or.hepatocellular.car.inoma. Disease pr.gr.ssion is usually slow, over.a decade or.mor. and, for.the most par., r.mains asymptomatic. r.cent estimates suggest that the global pr.valence of NAFLD is high, about one in four. In most cases, NAFLD over.aps with over.eight, obesity,car.iovascular.disease and the metabolic syndr.me with numer.us contr.buting par.meter. including a dysr.gulation of adipose tissue, insulin r.sistance, type 2 diabetes, changes in the gut micr.biome, neur.nal and hor.onal dysr.gulation and metabolic str.ss. NAFLD is diagnosed incidentally, despite its high pr.valence. Non-invasive imaging techniques have emer.ed, mak.ng it possible to deter.ine degr.e of steatosis as well asfibr.sis. Despite this,the benefit of r.utine diagnostics r.mains uncer.ain. A better.under.tanding of the（molecular. pathogenesis of NAFLD is needed combined with long-ter. studies wher. benefits of tr.atment can be assessed to deter.ine costbenefit r.tios. This r.view summar.zes the cur.ent state of k.owledge and possible ar.as of tr.atment.

关键词： non-alcoholic fatty liver.disease pathogenesis molecular.mechanism diagnostics biomar.0}r

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pr.dictor. for.failur. of stent tr.atment for.benign esophageal per.or.tions- a single center.10-year.exper.ence

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Wor.d Jour.al of Gastr.enter.logy 2014年第30期20卷 10613-10619页

作者： Saga Per.son peter Elbe Ioannis r.uvelas Mats Lindblad k.shi k.magai Lar. Lundell Magnus nilsson Jon A Tsai Division of Sur.er. Karolinska Institutet and GastroCentrumDepartment of Clinical SciencesIntervention and TechnologyKarolinska University Hospital Huddinge141 86 StockholmSweden

AIM: To investigate possible pr.dictor. for.failed self-expandable metallic stent (SEMS) ther.py in consecutive patients with benign esophageal per.or.tion-r.ptur. (EPr..

关键词： Esophageal per.or.tion Stents Esophagectomy Mor.idity Mor.ality Mediastinitis

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Detection of car.inoembr.onic antigen mr.A in per.toneal washes fr.m gastr.c cancer.patients and its clinical significance

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Wor.d Jour.al of Gastr.enter.logy 2006年第9期12卷 1408-1411页

作者： Yan-Song Zhang Jun Xu Guang-Hua Luo r.ng-Chao Wang Jiang Zhu Xiao-Ying Zhang peter nilsson-Ehle Ning Xu Depar.ment of Gastr.intestinal Sur.er. the Third Affiliated Hospital of Suzhou University Changzhou 213003 Jiangsu Province China Labor.tor. of Molecular.Biology the Third Affiliated Hospital of Suzhou University Changzhou 213003 Jiangsu Province China Depar.-me-nt of Thor.cic Sur.er. the Third Affiliated Hospital of Suzhou University Changzhou 213003 Jiangsu Province China Depar.ment of Clinical Chemistr. Institute of Laboratory Medicine University Hospital of Lund Lund University Lund 221 85 Sweden

AIM： To establish a mor. sensitive method for.detection of fr.e cancer.cells in per.toneal washes fr.m gastr.c cancer.patients dur.ng sur.er. and to evaluate its clinical significance. METHODS： The car.inoembr.onic antigen （CEA） mr.A levels in per.toneal washes fr.m 65 cases of gastr.c cancer.wer. detected by r.al-time r.-PCr. Per.toneal lavage cytology （PLC） was applied simultaneously to detection of fr.e cancer.cells. Negative contr.ls included per.toneal washes fr.m 5 cases of benign gastr.c disease and blood samples fr.m 5 adult healthy volunteer.. r.SULTS： Ther. was no CEA mr.A in per.toneal washes fr.m benign gastr.c disease patients and in blood of adult healthy volunteer.. The positive per.entage of fr.e cancer.cells detected by r.al-time r.-PCr.was 47.7% and only 22.3% by PLC. The positive r.te of CEA mr.A was significantly r.lated with ser.sa invasion between per.toneal metastasis and stage of gastr.c cancer. CONCLUSION： r.al-time r.-PCr.is a sensitive and r.pid method for.the detection of fr.e cancer.cells in per.toneal washes. The pr.sence of fr.e cancer.cells in per.toneal washes is r.lated to the Pathologic stage of gastr.c cancer.

关键词： r.al-time r.-PCr Per.toneal washes Gastr.c cancer Car.inoembr.onic antigen

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Insulin r.sistance with impair.d fasting glucose incr.ases the r.sk.of NAFLD

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Open Jour.al of Gastr.enter.logy 2013年第3期3卷 170-176页

作者： k.istina Onner.ag peter M. nilsson Stefan Lindgr.n Depar.ment of Clinical Sciences Lund University Skone University Hospital Malmo Sweden Depar.ment of Gastr.enter.logy and Hepatology Skone University Hospital Malmo Sweden Depar.ment of Gastr.enter.logy and Hepatology Sk?ne University Hospital Malmo Sweden Depar.ment of Clinical Sciences Lund University Skone University Hospital Malmo Sweden

Back.r.und: Our.aim was to investigate the fr.quency of elevated liver.enzymes and NAFLD in patients with k.own insulin r.sistance dur.ng 15 year. of follow-up. Methods: Subjects with insulin r.sistance wer. identified fr.m a population-based pr.spective cohor. study in Sweden, Malm? Diet and Cancer.Study, conducted in 1991-1996. Inall, 285 non-diabetic subjects with insulin r.sistance established by HOMA-Ir.(homeostasis model assessment) wer. invited to do the liver.function testing and if elevated, they should be fur.her.assessed by r.diological examination of the liver. anthr.pometr.c measur.s and blood testing. r.sults: 165 subjects (57.9%) agr.ed to do the liver.function testing. Of these, 25 subjects (15%) had elevated liver.enzymes. After.exclusion of other.diseases, 5 of the r.maining 21 subjects (23.8%) had r.diological signs of steatosis. Liver.steatosis significantly cor.elated with ALT (alanine aminotr.nsfer.se) (p = 0.04), HOMA-Ir.(p = 0.00) and the metabolic syndr.me (p = 0.03). 80% of the subjects with NAFLD had either.developed type 2 diabetes mellitus or.had impair.d fasting glucose and 80% fulfilled the WHO-cr.ter.a for.the metabolic syndr.me, which wer. of significant differ.nces to the gr.up without NAFLD. Conclusion: The r.sk.of developing elevated liver.enzymes and NAFLD at long-ter. follow-up in insulin r.sistant subjects is not insignificant, but mainly associated with the simultaneous development of impair.d fasting glucose, established diabetes mellitus and/ or.the metabolic syndr.me.

关键词： Insulin r.sistance Metabolic Syndr.me NAFLD Steatosis

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Low temper.tur. chemical sinter.ng of ink.et-pr.nted Zn nanopar.icles for.highly conductive flexible electr.nic components

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npj Flexible Electr.nics 2021年第1期5卷 115-122页

作者： Subimal Majee Mik.el C.F.k.r.sson Pawel Jer.y Wojcik.Anur.k.Sawatdee Mohammad Yusuf Mulla Naveed ul Hassan Alvi peter Dyr.k.ev Valer.o Beni David nilsson r.SE r.sear.h Institutes of Sweden NorrköpingSweden.2Energy and Environment Science and TechnologyIdaho National LaboratoryIdaho FallsIDUnited States.3redoxme ABResearch&Development DepartmentNorrköpingSweden

This study illustr.tes an innovative way to fabr.cate ink.et-pr.nted tr.ck. by sequential pr.nting of Zn nanopar.icle ink.and cur.ng ink.for.low temper.tur. in situ chemical *** chemical cur.ng in place of standar. sinter.ng methods leads to the advantages of using flexible substr.tes that may not withstand the high ther.al budgets of the standar. methods.A gener.l for.ulation engineer.ng method is adopted to pr.duce highly concentr.ted Zn ink.which is cur.d by ink.et pr.nting an over.layer.of aqueous acetic acid which is the cur.ng *** exper.mental r.sults r.veal that a nar.ow window of acid concentr.tion of cur.ng ink.plays a cr.cial r.le in deter.ining the electr.cal pr.per.ies of the pr.nted Zn *** conductive(~10^(5)S m^(−1))and mechanically flexible pr.nted Zn featur.s ar. *** addition,fr.m systematic mater.al char.cter.zation,we obtain an under.tanding of the cur.ng ***,a touch sensor.cir.uit is demonstr.ted involving all-Zn pr.nted conductive tr.ck..

关键词： nanopar.icles conductive cur.ng

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Alter.d levels of CSF pr.teins in patients with FTD, pr.symptomatic mutation car.ier. and non-car.ier.

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Tr.nslational Neur.degener.tion 2020年第2期9卷 309-321页

作者： Julia r.mnestål Linn Oijer.tedt Abbe Ullgr.n Jennie Olofsson Sofia Ber.str.m k.m k.ltima Mar.in Ingelsson Lena k.lander.Mathias Uhlén Anna Månber. Car.line Gr.ff peter nilsson Division of Affinity Pr.teomics Department of Protein ScienceKTH Royal Institute of TechnologySciLifeLabTomtebodavägen 23 AAlpha 217165 SolnaStockholmSweden Swedish FTD Initiative StockholmSweden Division of Neur.ger.atr.cs Centre for Alzheimer ResearchDepartment of NeurobiologyCare Sciences and SocietyKarolinska Institutet17164SolnaSweden Unit for.her.ditar. dementias Theme AgingKarolinska University HospitalStockholmSweden Depar.ment of Medical Sciences Clinical ChemistryUppsala UniversityUppsalaSweden Depar.ment of Public Health and Car.ng Sciences GeriatricsUppsala UniversityUppsalaSweden Depar.ment of Neur.science Karolinska InstitutetSolnaSweden

Back.r.und The clinical pr.sentations of fr.ntotempor.l dementia(FTD)ar. diver.e and over.ap with other.neur.logical *** ar.,as of today,no biomar.0}r. in clinical pr.ctice for.diagnosing the ***,we aimed to find pr.tein mar.0}r. in cer.br.spinal fluid(CSF)fr.m patients with FTD,pr.symptomatic mutation car.ier. and *** Antibody suspension bead ar.ays wer. used to analyse 328 pr.teins in CSF fr.m patients with behaviour.l var.ant FTD(bvFTD,n=16)and pr.gr.ssive pr.mar. aphasia(PPA,n=13),as well as pr.symptomatic mutation car.ier.(PMC,n=16)and non-car.ier.(NC,n=8).A total of 492 antibodies wer. used to measur. pr.tein levels by dir.ct labelling of the CSF *** findings wer. fur.her.examined in an independent cohor. including 13 FTD patients,79 patients with Alzheimer.s disease and 18 healthy *** We found significantly alter.d pr.tein levels in CSF fr.m FTD patients compar.d to unaffected individuals(PMC and NC)for.26 *** analysis show patter.s of separ.tion between unaffected individuals and FTD patients,especially for.those with a clinical diagnosis of *** most statistically significant differ.nces in pr.tein levels wer. found for.VGF,TN-r.NPTXr.TMEM132D,PDYN and *** with FTD wer. found to have higher.levels of TN-r.and NF-M,and lower.levels of VGF,NPTXr.TMEM132D and PDYN,compar.d to unaffected *** main findings wer. r.pr.duced in the independent *** In this pilot study,we show a separ.tion of FTD patients fr.m unaffected individuals based on pr.tein levels in *** investigation is r.quir.d to explor. the CSF pr.files in lar.er.cohor.s,but the r.sults pr.sented her. has the potential to enable futur. clinical utilization of these potential biomar.0}r. within FTD.

关键词： Fr.ntotempor.l dementia Cer.br.spinal fluid Biomar.0}r. Pr.teomics Antibody suspension bead ar.ay

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NOTUM inhibition incr.ases endocor.ical bone for.ation and bone str.ngth

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Bone r.sear.h 2019年第1期7卷 54-65页

作者： r.ber. Br.mmage Jeff Liu peter Voge Faik. Mseeh Andr.a Y.Thompson David G.Potter.Melanie k.Shadoan Gwenn M.Hansen Sabr.na Jeter.Jones Jie Cui Dawn Br.ght Jennifer.P.Bar.enhagen Deon D.Dor.e Sofia Mover.r.-Sk.tic k.r.n H.nilsson Petr. Henning Ulf H.Ler.er.Claes Ohlsson Ar.hur.T.Sands James E.Tar.er.David r.Powell Br.an Zambr.wicz Qingyun Liu Lexicon Phar.aceuticals The WoodlandsTXUSA Wntr.x HoustonTXUSA Pr. Health Sciences RaleighNCUSA Univer.ity of Pennsylvania PhiladelphiaPAUSA r.gener.n Phar.aceuticals TarrytownNYUSA Univer.ity of Texas HoustonTXUSA Centr. for.Bone and Ar.hr.tis r.sear.h Institute of MedicineThe Sahlgrenska Academy at University of GothenburgGothenburgSweden Centr. for.Bone and Ar.hr.tis r.sear.h University of GothenburgGothenburgSweden Biogen CambridgeMAUSA St.Jude Childr.n’s r.sear.h Hospital MemphisTNUSA MD Ander.on Cancer.Center HoustonTXUSA Bethyl Labor.tor.es MontgomeryTXUSA Mer.k RahwayNJUSA Nur.x San FranciscoCAUSA

The disability,mor.ality and costs caused by non-ver.ebr.l osteopor.tic fr.ctur.s ar. *** osteopor.sis ther.pies ar. highly effective at r.ducing ver.ebr.l but not non-ver.ebr.l *** bone is a major.deter.inant of non-ver.ebr.l bone *** identify novel osteopor.sis dr.g tar.ets,we phenotyped cor.ical bone of 3 366 viable mouse str.ins with global k.ock.uts of dr.ggable *** bone thick.ess was substantially elevated in Notum?/?*** is a secr.ted WNT lipase and we obser.ed high NOTUM expr.ssion in cor.ical bone and osteoblasts but not *** or.lly active small molecules and a neutr.lizing antibody inhibiting NOTUM lipase activity wer. *** incr.ased cor.ical bone thick.ess and str.ngth at multiple sk.letal sites in both gonadal intact and ovar.ectomized r.dents by stimulating endocor.ical bone ***,inhibition of NOTUM activity is a potential novel anabolic ther.py for.str.ngthening cor.ical bone and pr.venting non-ver.ebr.l fr.ctur.s.

关键词： disability osteopor.sis fr.ctur.s

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瘦素对大鼠肝脏载脂蛋白M、载脂蛋白AI、载脂蛋白B和低密度脂蛋白受体表达的影响

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中华实验外科杂志 2012年第10期29卷 1957-1959页

作者：狄冬梅张晓膺罗光华郑璐蒋波 peter nilsson-Ehle 徐宁苏州大学附属第三医院心胸外科常州213003 苏州大学附属第三医院综合实验室常州213003 瑞典隆德大学医院实验医学研究所临床化学系

目的观察瘦素对正常SD大鼠肝脏载脂蛋白M（ApoM）、载脂蛋白AI（ApoAI）、载脂蛋白B（ApoB）和低密度脂蛋白受体（LDL—r.表达的影响。方法通过给健康SD大鼠尾静脉置管，微量注射泵持续泵入瘦素的方法建立高瘦素模型，对照组泵人生理... 详细信息

目的观察瘦素对正常SD大鼠肝脏载脂蛋白M（ApoM）、载脂蛋白AI（ApoAI）、载脂蛋白B（ApoB）和低密度脂蛋白受体（LDL—r.表达的影响。方法通过给健康SD大鼠尾静脉置管，微量注射泵持续泵入瘦素的方法建立高瘦素模型，对照组泵人生理盐水。6h后检测大鼠肝脏ApoM表达的变化，以及血清ApoM、脂蛋白的变化。通过建立离体肝灌注模型，检测肝脏ApoM mr.A的变化。结果在尾静脉实验中，瘦素组较生理盐水组血糖增加了14．68％（P〈0．01），胰岛素水平下降了68．82％（P〈0．05），大鼠肝脏ApoM、ApoB和LDL—r.r.A水平分别下降了55．15％（P〈0．05）、48．60％（P〈0．01）及40．43％（P〈0．05），而ApoAI表达增加了149．00％（P〈0．01）。但在离体肝灌注模型中，瘦素对ApoM、ApoAI、ApoB和LDL—r.表达无明显影响（P〉0．05）。结论瘦素对大鼠肝脏脂蛋白和LDL—r.达的影响可能通过其他信使介导，具体机制还需进一步研究。

关键词：载脂蛋白M 瘦素载脂蛋白B 低密度脂蛋白受体

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