1 / 23

Speaker:Han , Ge Date:13 May 2014

Introduction to The Alzheimer’s Disease Related Genes. Speaker:Han , Ge Date:13 May 2014. Table of Content. §1 Introduction §2 The Alzheimer’s Disease related genes §3 Three FDA approved agents for Imaging of A β Plaques §4 Summary. Discovery and Classification.

lou
Download Presentation

Speaker:Han , Ge Date:13 May 2014

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Introduction to The Alzheimer’s Disease Related Genes Speaker:Han, Ge Date:13 May 2014

  2. Table of Content §1 Introduction §2 The Alzheimer’s Disease related genes §3 Three FDA approved agents for Imaging of Aβ Plaques §4 Summary

  3. Discovery and Classification Discoverywho: Dr.Allos Alzheimer(German psychiatrist) when:1906 • Classification • Familial Alzheimer’s disease (FAD) • Sporadical Alzheimer’s disease (SAD) AugusteDeter (the first person diagnosed with AD) Dr.Alois Alzheimer (1864~1915) http://en.wikipedia.org/wiki/Alzheimer%27s_disease

  4. Growth in the number of AD Actual and estimated number of new Alzheimer disease cases in the US through the year 2050 AD is estimated to have cost the world $604 billion in 2010 alone. These costs are staggering, particularly in light of predictions that the worldwide number of AD cases, currently estimated at 36 million, will triple by 2050. Mount, C.Downton, C. Nat. Med. 2006, 12, 780

  5. The hallmarks of AD Alzheimer's disease brain comparison Amyloid plaques and neurofibrillary tangles http://en.wikipedia.org/wiki/Alzheimer%27s_disease

  6. The Alzheimer’s Disease related genes

  7. AD related genes Alzheimer’s Disease is a genetically complex disease. Familial Alzheimer’s disease related genes :APP、Presenilin1 and Presenilin 2... Sporadical Alzheimer’s disease related gene :APOE4… zh.wikipedia.org/zh-cn/

  8. APP enzymolysis pathways N-terminal Two pathways exist for the processing of APP, one being nonamyloidogenic whilst the other pathway is amyloidogenic. Henry W. Querfurth, Frank M. LaFerla, N. Engl .J .Med. 2010; 362:329-344

  9. Formation of amyloid fibril Schematic representation of amyloid fibril David J. Hayne, SinChun Lim and Paul S. Donnelly.Chem .Soc .Rev.2014;

  10. 3D structure of Aβ42 fibrils Structural studies using fibrils formed from Aβ 42 peptides have given insight into the 3D structure of Aβ 42 fibrils . David J. Hayne, SinChun Lim and Paul S. Donnelly.Chem. Soc. Rev.2014;

  11. Presenilin(PS) HL-VI PS-1:70%~80% of FAD is related to the mutations in PS-1.(age of onset:40~50) PS-2:Some of FAD is related to the mutations in PS-2.(age of onset:50~60) extracellular intracellular The exact three-dimensional structure and function of PS remain unkonwn. Presenilintransmembrane structure diagram PS-1 PS-2 顾拥军，孙凤艳，J.Life Science,1997;5,9

  12. APOE The apoE proteolysis hypothesis suggests that, in response to stress or injuries, neuronal apoE expression is triggered to facilitate neuronal repair. However, neuronal apoE undergoes proteolytic cleavage, with apoE4 being more susceptible to the cleavage than apoE3, resulting in the formation of neurotoxic fragments. The apoE4 fragments enter the cytosol and cause mitochondrial impairment and cytoskeletal disruption. ApoE4 in AD Pathogenesis Yadong Huang ,Lennart Mucke.J.Cell.2012，1204-1223

  13. Analysis pipeline map to the chromosome The information of AD ralated genes contain: genesymbol、geneID、ensembl ID proteinID、ensembl ID2Chromosomeinfo

  14. Preliminary data processing TGM6、 SNAR-I、 STK11 、 CLMN 、 UTS2D 、 PGAM5P1 、 ITGA1 、 OSTNIL1-RAP 、 LEMD2 、 VSNL1 、 Sec11C 、 PPP1R3B 、 SLC28A1 、 MPP7 、 CAMK4 、 CACNA1G 、 ARHGAP20 、 RELN 、 PCDH11X 、 LIPC 、 RP11-341A22.2 、 PRRC2C 、 PPP1R37 、 RFC3 、 HRK 、 MS4A4A 、 MS4A4E 、 TREM 、BIN1、 SAP30L 、PVRL2 、EDIL3 、 MEGF10 、 CD2AP 、 CDON 、 FAM113B 、 ARID1B 、 ELMO1 、 VLDLR 、 MMP12 、 ANKRD55 、 ANO4 、 GAB2 、 ITGA6 、 FMN2 、 ZNF592 、APOE、 BCHE 、 ZNF224 、 MSRA 、 CRADD 、 ST18 、 GEMC1 、 SLC9A9 、 AFF1 、 BCAS3 、 DISC1、 PIK3R1 、 NKAIN2 、 CCDC50 、 ALPK3 、 DCHS2 、 FLJ45256 、 AC079250.1 、 FLJ33630 、 STK24 、 PAX2 、 CCDC134 、 STK32B 、 RP11-572M11.4 、 KCNV2 、 HECW1 、 VAT1L 、TOMM40、 RP11-291J9.2 、 SP6 、 MRPL10 、 OSBPL7 、 GPC6 、 ADAMTS9 、 EPHA1 、 CSMD1 、 TREM2 、 POLN 、 SLC4A8 、 ATXN7L1 、 SORL1 、 MIR1275 、 MIR1275 、 PPAPDC1A 、 GABRG3 、PICALM、CLU、APOC1 、PDE7B 、 NUAK1 、 PARVB 、 SASH1 、 ZNF320 、 RIMBP2 、 EFNA5 、 MAN2A1 、 DMXL1 、 MOBP 、 FRMD4A 、 LOC390956 、 LOC390958 、 MYO16 、 MTHFD1L 、 DIP2C 、 NCS1 、 CYCS 、 LIMS2 、 CNTNAP2、 AC015804.1 、 LOC100129500 、 C12orf75 、CR1、 FLJ37543 、 GRIN3B 、 BZW2 、 TSPAN13 、 TSPAN13 、 EFR3A 、 RP11-242G20.2 、 TTLL7 、 MLN、 NCR2、 MS4A6A、 LUZP2、 CUGBP2、 HMHA1、 PCNX、 SPON1、 RRAS2、 CEACAM16、 CTNNA2、 AC110611.1、 NFIB、 PLEKHG1、 EXOC4、 RNFT2、 SLC4A1AP、 BCL3、 AC008541.1、 MS4A、 MMP3、 AP003097.1、 PSMA1、SLC2A9、CD33、GLIS3、EPC2 Number:153 The AD related genes (GWASstudies) www.genome.gov/GWAStudies

  15. Gene frequency statistics APOE、TOMM40、APOC1:Genes locate on the chromosome 19. TREM2: Some other studies have found that the mutation of TREM2 could increase the risk of AD.

  16. Gene location on chromosome APOE Chromosome 19 has 14 AD ralated genes. Chromosome 6 , 5 and 11 also have 13,10,9 AD related genes respectively. So if there are genes like APOE locate on them? Chromosome 21 has no AD related genes on it ,but APP is on it. And Why?

  17. Three FDA approved agents for Imaging of Aβ Plaques

  18. The information of the 3 agents (1) (2) Amyvid(Diarylalkene analogs) Vizaml(Planar heteroaromatic analogs) Company : Eli Lilly Year : 2012.10 Company:General Electric Company Year:2013.10 (3) They are just the agents to detect and specific binding to Aβ ,not the drugs to treat or alleviate AD symptoms. Florbetaben(Diarylalkene analogs) Company:Pfizer Year:2014.3 N. S. Mason, C. A. Mathis and W. E. Klunk, J. LabelledCompd. Radiopharm., 2013, 56, 89.

  19. PET PET(Positron emission tomography,正电子发射计算机断层扫描) is a non-invasive molecular imaging technique that relies on the detection of radioactivity emitted from a positron-emitting isotope that is incorporated into a molecular tracer or imaging agent. The emitted positron annihilates releasing two gamma photons travelling in opposite directions. Detection of the emitted photons allows the generation of an image with a spatial resolution of 3–5 mm with high sensitivity. http://en.wikipedia.org/wiki/Positron_emission_tomography

  20. The image of PET Axial slices of  Vizaml scans are shown for 2 representative subjects, cognitively normal control with low tracer retention (top) and AD patient with high tracer retention in cortex relative to cerebellum, reflecting widespread fibrillaramyloid (bottom). Landau SM,BreaultC,JoshiAD,PontecorviM,MathisCA,JagustWJ,Mintun MA,J Nucl Med,2013;54:70-7.

  21. Summary • The full details of the role Aβ plaques, APOE, PS-1, and PS-2 play in congnitive impair in Alzheimer’s Disease remain a mystery. • AD ralated genes are abundant at chromosome 19. Maybethere are genes like APOE locate on chromosome 6,5 and 11. • The development of these agents for imaging of Aβ plaques might provide the means for early non-invasive detection of Aβ plaques in AD and pre-AD subjects.

  22. Acknowledge Prof. Wu Prof. Ye XudongZou Yang Wang ……

  23. Thank you for your attention!

More Related