Dementia with Lewy Bodies(DLB)was initially identified and confirmed primarily by pathology,but is soon to be incorporated into the Diagnostic and Statistical Manual criteria as a clinical disease entity.Despite these...Dementia with Lewy Bodies(DLB)was initially identified and confirmed primarily by pathology,but is soon to be incorporated into the Diagnostic and Statistical Manual criteria as a clinical disease entity.Despite these advances over more than 20 years,current data suggest that the sensitivity of accurate clinical diagnosis of DLB is still very low,although there is mounting evidence that supportive features may increase diagnostic accuracy.Although DLB remains easy to identify pathologically with different cellular pathologies differentiating it from other dementia syndromes,pathological identification using only Lewy body pathology has been shown to be inaccurate due to overlap with patients without dementia symptoms.A number of studies now suggest that a combination of cellular pathologies,which include α-synuclein and β-amyloid deposition as well as dopamine denervation,assist with differentiating this dementia syndrome from others.The clinical and pathological overlap with the tauopathy of Alzheimer’s disease still remains to be clarified.To determine more robust and independent clinicopathological correlates from Alzheimer’s disease,longitudinal prospective studies,using specific clinical batteries on dementia patients reaching the proposed criteria for DLB,with post-mortem assessment of the multiple pathologies associated with dementia,are required.Identifying genetic causes for DLB is another approach to investigate the pathogenesis of DLB.However this approach has been hindered to date by difficulties with identifying DLB clinically.The use of novel techniques is likely to advance knowledge on the pathogenesis of DLB and assist with redefining clinical and pathologic diagnostic criteria.To achieve the goal of more accurate clinical diagnosis of DLB,breakthroughs are necessary on the pathogenesis of DLB.展开更多
Both fresh-frozen and formalin-fixed,paraffinembedded（FFPE）human brain tissues are invaluable resources for molecular genetic studies of central nervous system diseases,especially neurodegenerative disorders.To iden...Both fresh-frozen and formalin-fixed,paraffinembedded（FFPE）human brain tissues are invaluable resources for molecular genetic studies of central nervous system diseases,especially neurodegenerative disorders.To identify the optimal method for DNA extraction from human brain tissue,we compared methods on differently-processed tissues.Fragments of LRRK2 and MAPT（257 bp and 483 bp/245 bp）were amplified for evaluation.We found that for FFPE samples,the success rate of DNA extraction was greater when using a commercial kit than a laboratory-based method（successful DNA extraction from 76%versus 33%of samples）.PCR amplicon size and storage period were key factors influencing the success rate of DNA extraction from FFPE samples.In the fresh-frozen samples,the DNA extraction success rate was 100%using either a commercial kit（QIAamp DNA Micro）or a laboratorybased method（sample boiling in 0.1 mol/L NaOH,followed by proteinase K digestion,and then DNA extraction using Chelex-100）regardless of PCR amplicon length or tissue storage time.Although the present results demonstrate that PCR-amplifiable genomic DNA can be extracted from both fresh-frozen and FFPE samples,fresh brain tissue is recommended for DNA extraction in future neuropathological studies.展开更多
基金志谢 此研究获得澳大利亚老年性痴呆基金会（Alzheimer’s Australian Association）和澳大利亚.中国科学院国际交流基金（Australian-Chinese Academy of Science International Exchange Grant）的支持.剑桥行为量表和剑桥认知量表的中文翻译获得许可,欲应用此量表进行临床观察的医生请与通信作者联系或登陆http：//www.ftdrg.org/research/test-downloads/.Heidi Cartwright教授为此讲座准备了病理图片,脑组织病理取材自澳大利亚威尔士王子医学研究所的人脑组织库.该研究所的梁华征和Clement Loy博士,英国Sussex大学的Brendan Weekes医师以及天坛医院的张玉梅医师参与了量表的翻译工作
基金YH is supported by a Goldstar Award of University of New South Wales.GMH has a NHMRC Senior Principal Research Fellowship(630434).
文摘Dementia with Lewy Bodies(DLB)was initially identified and confirmed primarily by pathology,but is soon to be incorporated into the Diagnostic and Statistical Manual criteria as a clinical disease entity.Despite these advances over more than 20 years,current data suggest that the sensitivity of accurate clinical diagnosis of DLB is still very low,although there is mounting evidence that supportive features may increase diagnostic accuracy.Although DLB remains easy to identify pathologically with different cellular pathologies differentiating it from other dementia syndromes,pathological identification using only Lewy body pathology has been shown to be inaccurate due to overlap with patients without dementia symptoms.A number of studies now suggest that a combination of cellular pathologies,which include α-synuclein and β-amyloid deposition as well as dopamine denervation,assist with differentiating this dementia syndrome from others.The clinical and pathological overlap with the tauopathy of Alzheimer’s disease still remains to be clarified.To determine more robust and independent clinicopathological correlates from Alzheimer’s disease,longitudinal prospective studies,using specific clinical batteries on dementia patients reaching the proposed criteria for DLB,with post-mortem assessment of the multiple pathologies associated with dementia,are required.Identifying genetic causes for DLB is another approach to investigate the pathogenesis of DLB.However this approach has been hindered to date by difficulties with identifying DLB clinically.The use of novel techniques is likely to advance knowledge on the pathogenesis of DLB and assist with redefining clinical and pathologic diagnostic criteria.To achieve the goal of more accurate clinical diagnosis of DLB,breakthroughs are necessary on the pathogenesis of DLB.
基金supported by a Personnel Training Award from the Department of Health, Hebei Province, a Goldstar Award from the University of New South Wales, and an NHMRC Senior Principal Research Fellowship (630434)
文摘Both fresh-frozen and formalin-fixed,paraffinembedded（FFPE）human brain tissues are invaluable resources for molecular genetic studies of central nervous system diseases,especially neurodegenerative disorders.To identify the optimal method for DNA extraction from human brain tissue,we compared methods on differently-processed tissues.Fragments of LRRK2 and MAPT（257 bp and 483 bp/245 bp）were amplified for evaluation.We found that for FFPE samples,the success rate of DNA extraction was greater when using a commercial kit than a laboratory-based method（successful DNA extraction from 76%versus 33%of samples）.PCR amplicon size and storage period were key factors influencing the success rate of DNA extraction from FFPE samples.In the fresh-frozen samples,the DNA extraction success rate was 100%using either a commercial kit（QIAamp DNA Micro）or a laboratorybased method（sample boiling in 0.1 mol/L NaOH,followed by proteinase K digestion,and then DNA extraction using Chelex-100）regardless of PCR amplicon length or tissue storage time.Although the present results demonstrate that PCR-amplifiable genomic DNA can be extracted from both fresh-frozen and FFPE samples,fresh brain tissue is recommended for DNA extraction in future neuropathological studies.
