医学精品课件：脑库建设.pptx

1、脑库建设与神经病理学竺可青2014-3-11DonorResearcherThe Art of Brain Banking1.Brain tissue-different brain areas-paraffin embeddedimmunostainings-frozenQ-PCR,microarrays,proteomics-freshcell cultures2.Cerebrospinal fluid-ventricular CSFbiomarker reserach,proteomics3.DNA-from bloodgenetics coupled to pathology4.Ext

2、ensive neuropathological report 可以提供临床病理报告 Clinical data are available Information about time of death,post-mortem delay,brain weight,pH CSF5.Special requests possible 研究人员可以提出特殊要求脑库用处What can you apply for.and what do you getCNS disorders represented in tissue samples collected in BrainNet Europe c

3、entresNeurodegenerative disorders and dementia(15 banks)Prion disorders(12 banks)Multiple sclerosis(4 banks)Vascular disorders(6 banks)Epilepsy(3 banks)Psychiatric disorders(5 banks)CNS tumours(6 banks)HIV/AIDS(4 banks)Inflammatory infective disorders(3 banks)Motor neuron disease(1 bank)Parkinsons d

4、isease(2 banks)Huntingtons disease(2 banks)Trauma(1 bank)Metabolic disorders(1 bank)Drug addiction(1 bank)Malformations and congenital disorders(5 banks)Muscle/nerves(2 banks)Control brains(12 banks)BrainNet Europe供者填表对无自主能力者，由家属填表Autopsy protocals 取脑程序 control Alzhemiers disease Parkinsons disease

5、FTLDs MS MSA PSP HD Depression Schizophrenia样本取材与诊断的标准化样本取材与诊断的标准化神经病理诊断神经病理诊断准确的病理诊断至关重要准确的病理诊断至关重要Sometimes senile plaques can already be seen in HE sectionsMisfolded proteins disturbed degradation and aggregationMisfolding andaggregationTau mutationTau Picks diseaseTDP Progranuline mut.prionsnorm

6、allyAbeta in ADAbeta in CAAA-synuclein in PDhuntingtinPrimary Neurodegenerative disorders Molecular diagnosis神经系统变性疾病的分子诊断神经系统变性疾病的分子诊断TauopathiesFTLD-Tau(chromosome 17T)3 R tau and/or 4 R tauPSP(4 R tau)CBD(4 R tau)Senile tauopa(4 R tau)Argyrophilic grain disease(4 R tau)Picks disease(3 R tau)TDPFT

7、LDspFTLD-TDPPro-granulinmutationsChrom.9 mutationsC orf27TDP-mutationsInclusionsIn 25%ADFUSFTLDFUSMut.Rare Sporadic FormsBasophilicInclusionDisease4%ALSAbetaADMCIagingCAA prionsCJD sp.CJD hered.GSSFFIPRPrTriplet diseaseProteinsHDhuntingtinDRPL atrophyJunctophilinSCAataxinFAFrataxina-synucleinPDPDDDL

8、BMSAAD-Braak stages for amyloid are quite rough:Stage A:senile plaques in parahippocampal and frontobasal regionsStage B:in between stage A and CStage C:neuritic plaques everywhere,also in the occipital cortex Diffuse plaque Classic plaque“老年性痴呆老年性痴呆”？AD-Braak stages for neurofibrillary tangles(nft)

9、Stage 1:few nft in parahippocampal gyrus PHGStage 2:in between stage 1 and 3Stage 3:many nft in PHG and cornu Ammonis field 1(CA1)Stage 4:stage 3 plus many nft in temporal neocortexStage 5:stage 4 plus many nft in frontal and/or parietal neocortexStage 6:stage 5 plus many nft in occipital neocortex

10、Braak stages for Lewy body pathology in Parkinsons disease诊断的准确性诊断的准确性 Stage 1:Lewy pathology restricted to medulla oblongata Stage 2:extending to locus coeruleus Stage 3:extending to substantia nigra Stage 4:extending to limbic areas Stage 5:extending to neocortex Stage 6:reaching the motor cortex

11、Multiple sclerosis(MS)诊断的进一步细化诊断的进一步细化Staging and characterization of post mortem MS lesions(van der Valk and De Groot,2000)and(B et al.,2006):0=normal appearing white matter(hardly any HLA reactivity,no demyelination)1=reactive(groups of HLA-positive microglial cells,no demyelination)2=active lesio

12、n(demyelination,HLA positive microglial cells throughout the lesion)Sub-score 1-3 reflects degree of activation of HLA positive microglial cells:ramified appearance=1 up to big rounded foamy morphology=33=chronic active lesion(hypocelular gliotic centre,active border with HLA-positive macrophages/mi

13、croglial cells)Subscore 1-3 reflects degree of activation of HLA positive microglial cells:ramified appearance=1 up to big rounded foamy morphology=34=gliotic inactive hypocellular lesion,with some HLA-positive microgliosis5=grey matter lesion(for cortex not for spinal cord):Type I=mixed grey-white

14、matter lesionType II=grey matter lesion Type III=subpial demyelinationType IV=grey matter lesion that stops exactly at the border with white matter 6=shadow plaque样本储存样本储存(冰冻标本和石蜡切片）冰冻标本和石蜡切片）临床资料与档案管理临床资料与档案管理数据库与样本提供数据库与样本提供研究者研究项目申请表研究者研究项目申请表（正规化）（正规化）样本的使用样本的使用欧洲脑库的侧重点欧洲脑库的侧重点Familial ADGlobal atrophy,mostlyfrontal,temporal and parietal and hippocampus脑标本的取得脑标本的取得