Neurobiology of Aging
Volume 31, Issue 4 , Pages 549-566 , April 2010

Neuronal gene expression in non-demented individuals with intermediate Alzheimer's Disease neuropathology

  • Winnie S. Liang

      Affiliations

    • Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
    • Arizona Alzheimer's Disease Consortium, Phoenix, AZ 85006, USA
    • ,
  • Travis Dunckley

      Affiliations

    • Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
    • Arizona Alzheimer's Disease Consortium, Phoenix, AZ 85006, USA
    • ,
  • Thomas G. Beach

      Affiliations

    • Arizona Alzheimer's Disease Consortium, Phoenix, AZ 85006, USA
    • Sun Health Research Institute, Sun City, AZ 85351, USA
    • ,
  • Andrew Grover

      Affiliations

    • Arizona Alzheimer's Disease Consortium, Phoenix, AZ 85006, USA
    • Sun Health Research Institute, Sun City, AZ 85351, USA
    • ,
  • Diego Mastroeni

      Affiliations

    • Arizona Alzheimer's Disease Consortium, Phoenix, AZ 85006, USA
    • Sun Health Research Institute, Sun City, AZ 85351, USA
    • ,
  • Keri Ramsey

      Affiliations

    • Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
    • ,
  • Richard J. Caselli

      Affiliations

    • Arizona Alzheimer's Disease Consortium, Phoenix, AZ 85006, USA
    • Department of Neurology, Mayo Clinic, Scottsdale, AZ 85259, USA
    • ,
  • Walter A. Kukull

      Affiliations

    • National Alzheimer's Coordinating Center, Seattle, WA 98105, USA
    • ,
  • Daniel McKeel

      Affiliations

    • Washington University Alzheimer's Disease Research Center, St. Louis, MO 63108, USA
    • ,
  • John C. Morris

      Affiliations

    • Washington University Alzheimer's Disease Research Center, St. Louis, MO 63108, USA
    • ,
  • Christine M. Hulette

      Affiliations

    • Duke University Alzheimer's Disease Research Center, Durham, NC 27705, USA
    • ,
  • Donald Schmechel

      Affiliations

    • Duke University Alzheimer's Disease Research Center, Durham, NC 27705, USA
    • ,
  • Eric M. Reiman

      Affiliations

    • Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
    • Arizona Alzheimer's Disease Consortium, Phoenix, AZ 85006, USA
    • Banner Alzheimer's Institute, Phoenix, AZ 85006, USA
    • ,
  • Joseph Rogers

      Affiliations

    • Arizona Alzheimer's Disease Consortium, Phoenix, AZ 85006, USA
    • Sun Health Research Institute, Sun City, AZ 85351, USA
    • ,
  • Dietrich A. Stephan

      Affiliations

    • Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
    • Arizona Alzheimer's Disease Consortium, Phoenix, AZ 85006, USA
    • Navigenics, Redwood Shores, CA 94065, USA
    • Corresponding Author InformationCorresponding author at: Neurogenomics Division, The Translational Genomics Research Institute, 445 North Fifth Street, Phoenix, AZ 85004, USA. Tel.: +1 602 343 8727; fax: +1 602 343 8844.

Received 3 December 2007 ,Revised 2 May 2008 ,Accepted 6 May 2008.

References 

  1. Angelie E, Bonmartin A, Boudraa A, Gonnaud PM, Mallet JJ, Sappey-Marinier D. Regional differences and metabolic changes in normal aging of the human brain: proton MR spectroscopic imaging study. Am. J. Neuroradiol. 2001;22(1):119–127
  2. Barrachina M, Castano E, Ferrer I. TaqMan PCR assay in the control of RNA normalization in human post-mortem brain tissue. Neurochem. Int. 2006;49(3):276–284
  3. Belizaire R, Komanduri C, Wooten K, Chen M, Thaller C, Janz R. Characterization of synaptogyrin 3 as a new synaptic vesicle protein. J. Comp. Neurol. 2004;470(3):266–281
  4. Benson DL, Colman DR, Huntley GW. Molecules, maps and synapse specificity. Nat. Rev. Neurosci. 2001;2(12):899–909
  5. Blesa R, Mohr E, Miletich RS, Hildebrand K, Sampson M, Chase TN. Cerebral metabolic changes in Alzheimer's disease: neurobehavioral patterns. Dementia. 1996;7(5):239–245
  6. Bobinski M, de Leon MJ, Convit A, De Santi S, Wegiel J, Tarshish CY, et al. MRI of entorhinal cortex in mild Alzheimer's disease. Lancet. 1999;353(9146):38–40
  7. Bouras C, Hof PR, Giannakopoulos P, Michel JP, Morrison JH. Regional distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of elderly patients: a quantitative evaluation of a one-year autopsy population from a geriatric hospital. Cereb. Cortex. 1994;4(2):138–150
  8. Boutajangout A, Boom A, Leroy K, Brion JP. Expression of tau mRNA and soluble tau isoforms in affected and non-affected brain areas in Alzheimer's disease. FEBS Lett. 2004;576(1–2):183–189
  9. Braak H, Braak E. The human entorhinal cortex: normal morphology and lamina-specific pathology in various diseases. Neurosci. Res. 1992;15(1–2):6–31
  10. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. (Berl.). 1991;82(4):239–259
  11. Brown NM, Torres AS, Doan PE, O’Halloran TV. Oxygen and the copper chaperone CCS regulate posttranslational activation of Cu, Zn superoxide dismutase. Proc. Natl. Acad. Sci. U.S.A. 2004;101(15):5518–5523
  12. Conrad C, Zhu J, Conrad C, Schoenfeld D, Fang Z, Ingelsson M, et al. Single molecule profiling of tau gene expression in Alzheimer's disease. J. Neurochem. 2007;103(3):1228–1236
  13. Convit A, Wolf OT, de Leon MJ, Patalinjug M, Kandil E, Caraos C, et al. Volumetric analysis of the pre-frontal regions: findings in aging and schizophrenia. Psychiatry Res. 2001;107(2):61–73
  14. Culotta VC, Klomp LW, Strain J, Casareno RL, Krems B, Gitlin JD. The copper chaperone for superoxide dismutase. J. Biol. Chem. 1997;272(38):23469–23472
  15. Davidson Y, Gibbons L, Pritchard A, Hardicre J, Wren J, Tian J, et al. Genetic associations between cathepsin D exon 2 C→T polymorphism and Alzheimer's disease, and pathological correlations with genotype. J. Neurol. Neurosurg. Psychiatry. 2006;77(4):515–517
  16. de Leon MJ, George AE, Stylopoulos LA, Smith G, Miller DC. Early marker for Alzheimer's disease: the atrophic hippocampus. Lancet. 1989;2(8664):672–673
  17. Du AT, Schuff N, Zhu XP, Jagust WJ, Miller BL, Reed BR, et al. Atrophy rates of entorhinal cortex in AD and normal aging. Neurology. 2003;60(3):481–486
  18. Ferreira A, Kao HT, Feng J, Rapoport M, Greengard P. Synapsin III: developmental expression, subcellular localization, and role in axon formation. J. Neurosci. 2000;20(10):3736–3744
  19. Fox NC, Warrington EK, Stevens JM, Rossor MN. Atrophy of the hippocampal formation in early familial Alzheimer's disease. A longitudinal MRI study of at-risk members of a family with an amyloid precursor protein 717Val-Gly mutation. Ann. N.Y. Acad. Sci. 1996;777:226–232
  20. Frisoni GB, Laakso MP, Beltramello A, Geroldi C, Bianchetti A, Soininen H, et al. Hippocampal and entorhinal cortex atrophy in frontotemporal dementia and Alzheimer's disease. Neurology. 1999;52(1):91–100
  21. Furukawa Y, Torres AS, O’Halloran TV. Oxygen-induced maturation of SOD1: a key role for disulfide formation by the copper chaperone CCS. Embo J. 2004;23(14):2872–2881
  22. Ginsberg SD, Che S, Counts SE, Mufson EJ. Shift in the ratio of three-repeat tau and four-repeat tau mRNAs in individual cholinergic basal forebrain neurons in mild cognitive impairment and Alzheimer's disease. J. Neurochem. 2006;96(5):1401–1408
  23. Ginsberg SD, Hemby SE, Lee VM, Eberwine JH, Trojanowski JQ. Expression profile of transcripts in Alzheimer's disease tangle-bearing CA1 neurons. Ann. Neurol. 2000;48(1):77–87
  24. Goedert M, Spillantini MG, Jakes R, Rutherford D, Crowther RA. Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease. Neuron. 1989;3(4):519–526
  25. Hackett JT, Cochran SL, Greenfield LJ, Brosius DC, Ueda T. Synapsin I injected presynaptically into goldfish mauthner axons reduces quantal synaptic transmission. J. Neurophysiol. 1990;63(4):701–706
  26. Harrison PJ, Wighton-Benn WH, Heffernan JM, Sanders MW, Pearson RC. Amyloid precursor protein mRNAs in Alzheimer's disease. Neurodegeneration. 1996;5(4):409–415
  27. Hemby SE, Trojanowski JQ, Ginsberg SD. Neuron-specific age-related decreases in dopamine receptor subtype mRNAs. J. Comp. Neurol. 2003;456(2):176–183
  28. Hilfiker S, Schweizer FE, Kao HT, Czernik AJ, Greengard P, Augustine GJ. Two sites of action for synapsin domain E in regulating neurotransmitter release. Nat. Neurosci. 1998;1(1):29–35
  29. Hyman BT, Van Hoesen GW, Damasio AR, Barnes CL. Alzheimer's disease: cell-specific pathology isolates the hippocampal formation. Science. 1984;225(4667):1168–1170
  30. Ivancevic V, Alavi A, Souder E, Mozley PD, Gur RE, Benard F, et al. Regional cerebral glucose metabolism in healthy volunteers determined by fluordeoxyglucose positron emission tomography: appearance and variance in the transaxial, coronal, and sagittal planes. Clin. Nucl. Med. 2000;25(8):596–602
  31. Jack CR, Petersen RC, Xu Y, O’Brien PC, Smith GE, Ivnik RJ, et al. Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease. Neurology. 1998;51(4):993–999
  32. Janz R, Sudhof TC, Hammer RE, Unni V, Siegelbaum SA, Bolshakov VY. Essential roles in synaptic plasticity for synaptogyrin I and synaptophysin I. Neuron. 1999;24(3):687–700
  33. Johnston JA, Norgren S, Ravid R, Wasco W, Winblad B, Lannfelt L, et al. Quantification of APP and APLP2 mRNA in APOE genotyped Alzheimer's disease brains. Brain Res. Mol. Brain Res. 1996;43(1–2):85–95
  34. Jovanovic JN, Czernik AJ, Fienberg AA, Greengard P, Sihra TS. Synapsins as mediators of BDNF-enhanced neurotransmitter release. Nat. Neurosci. 2000;3(4):323–329
  35. Jovanovic JN, Sihra TS, Nairn AC, Hemmings HC, Greengard P, Czernik AJ. Opposing changes in phosphorylation of specific sites in synapsin I during Ca2+-dependent glutamate release in isolated nerve terminals. J. Neurosci. 2001;21(20):7944–7953
  36. Kitano-Takahashi M, Morita H, Kondo S, Tomizawa K, Kato R, Tanio M, et al. Expression, purification and crystallization of a human tau-tubulin kinase 2 that phosphorylates tau protein. Acta Crystallogr. Sect. F: Struct. Biol. Cryst. Commun. 2007;63(Pt 7):602–604
  37. Kuwano R, Miyashita A, Arai H, Asada T, Imagawa M, Shoji M, et al. Dynamin-binding protein gene on chromosome 10q is associated with late-onset Alzheimer's disease. Hum. Mol. Genet. 2006;15(13):2170–2182
  38. LaFerla FM. Calcium dyshomeostasis and intracellular signalling in Alzheimer's disease. Nat. Rev. Neurosci. 2002;3(11):862–872
  39. Li L, Chin LS, Shupliakov O, Brodin L, Sihra TS, Hvalby O, et al. Impairment of synaptic vesicle clustering and of synaptic transmission, and increased seizure propensity, in synapsin I-deficient mice. Proc. Natl. Acad. Sci. U.S.A. 1995;92(20):9235–9239
  40. Liang WS, Dunckley T, Beach TG, Grover A, Mastroeni D, Ramsey K, et al. Altered neuronal gene expression in brain regions differentially affected by Alzheimer's Disease: a reference data set. Physiol. Genomics. 2008;
  41. Liang WS, Dunckley T, Beach TG, Grover A, Mastroeni D, Walker DG, et al. Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain. Physiol. Genomics. 2007;28(3):311–322
  42. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25(4):402–408
  43. Llinas R, Gruner JA, Sugimori M, McGuinness TL, Greengard P. Regulation by synapsin I and Ca(2+)-calmodulin-dependent protein kinase II of the transmitter release in squid giant synapse. J. Physiol. 1991;436:257–282
  44. Llinas R, McGuinness TL, Leonard CS, Sugimori M, Greengard P. Intraterminal injection of synapsin I or calcium/calmodulin-dependent protein kinase II alters neurotransmitter release at the squid giant synapse. Proc. Natl. Acad. Sci. U.S.A. 1985;82(9):3035–3039
  45. Loessner A, Alavi A, Lewandrowski KU, Mozley D, Souder E, Gur RE. Regional cerebral function determined by FDG-PET in healthy volunteers: normal patterns and changes with age. J. Nucl. Med. 1995;36(7):1141–1149
  46. Lohmann SM, Ueda T, Greengard P. Ontogeny of synaptic phosphoproteins in brain. Proc. Natl. Acad. Sci. U.S.A. 1978;75(8):4037–4041
  47. Lustbader JW, Cirilli M, Lin C, Xu HW, Takuma K, Wang N, et al. ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease. Science. 2004;304(5669):448–452
  48. Mariani E, Seripa D, Ingegni T, Nocentini G, Mangialasche F, Ercolani S, et al. Interaction of CTSD and A2M polymorphisms in the risk for Alzheimer's disease. J. Neurol. Sci. 2006;247(2):187–191
  49. Markesbery WR. Oxidative stress hypothesis in Alzheimer's disease. Free Radic. Biol. Med. 1997;23(1):134–147
  50. Matsui T, Ingelsson M, Fukumoto H, Ramasamy K, Kowa H, Frosch MP, et al. Expression of APP pathway mRNAs and proteins in Alzheimer's disease. Brain Res. 2007;1161:116–123
  51. Mattson MP, Chan SL. Neuronal and glial calcium signaling in Alzheimer's disease. Cell Calcium. 2003;34(4–5):385–397
  52. Melloni RH, DeGennaro LJ. Temporal onset of synapsin I gene expression coincides with neuronal differentiation during the development of the nervous system. J. Comp. Neurol. 1994;342(3):449–462
  53. Metsaars WP, Hauw JJ, van Welsem ME, Duyckaerts C. A grading system of Alzheimer disease lesions in neocortical areas. Neurobiol. Aging. 2003;24(4):563–572
  54. Mielke R, Herholz K, Grond M, Kessler J, Heiss WD. Clinical deterioration in probable Alzheimer's disease correlates with progressive metabolic impairment of association areas. Dementia. 1994;5(1):36–41
  55. Mielke R, Kessler J, Szelies B, Herholz K, Wienhard K, Heiss WD. Normal and pathological aging—findings of positron-emission-tomography. J. Neural. Transm. 1998;105(8–9):821–837
  56. Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, et al. The consortium to establish a registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology. 1991;41(4):479–486
  57. Moeller JR, Ishikawa T, Dhawan V, Spetsieris P, Mandel F, Alexander GE, et al. The metabolic topography of normal aging. J. Cereb. Blood Flow Metab. 1996;16(3):385–398
  58. Nixon RA. The calpains in aging and aging-related diseases. Ageing Res. Rev. 2003;2(4):407–418
  59. Oyama F, Shimada H, Oyama R, Titani K, Ihara Y. Beta-amyloid protein precursor and tau mRNA levels versus beta-amyloid plaque and neurofibrillary tangles in the aged human brain. J. Neurochem. 1993;60(5):1658–1664
  60. Oyama F, Shimada H, Oyama R, Titani K, Ihara Y. Differential expression of beta amyloid protein precursor (APP) and tau mRNA in the aged human brain: individual variability and correlation between APP-751 and four-repeat tau. J. Neuropathol. Exp. Neurol. 1991;50(5):560–578
  61. Papassotiropoulos A, Bagli M, Kurz A, Kornhuber J, Forstl H, Maier W, et al. A genetic variation of cathepsin D is a major risk factor for Alzheimer's disease. Ann. Neurol. 2000;47(3):399–403
  62. Preece P, Virley DJ, Costandi M, Coombes R, Moss SJ, Mudge AW, et al. Amyloid precursor protein mRNA levels in Alzheimer's disease brain. Brain Res. Mol. Brain Res. 2004;122(1):1–9
  63. Rae TD, Torres AS, Pufahl RA, O’Halloran TV. Mechanism of Cu, Zn-superoxide dismutase activation by the human metallochaperone hCCS. J. Biol. Chem. 2001;276(7):5166–5176
  64. Reich M, Ohm K, Angelo M, Tamayo P, Mesirov JP. GeneCluster 2.0: an advanced toolset for bioarray analysis. Bioinformatics. 2004;20(11):1797–1798
  65. Robinson CA, Clark AW, Parhad IM, Fung TS, Bou SS. Gene expression in Alzheimer neocortex as a function of age and pathologic severity. Neurobiol. Aging. 1994;15(6):681–690
  66. Rosahl TW, Spillane D, Missler M, Herz J, Selig DK, Wolff JR, et al. Essential functions of synapsins I and II in synaptic vesicle regulation. Nature. 1995;375(6531):488–493
  67. Rothstein JD, Dykes-Hoberg M, Corson LB, Becker M, Cleveland DW, Price DL, et al. The copper chaperone CCS is abundant in neurons and astrocytes in human and rodent brain. J. Neurochem. 1999;72(1):422–429
  68. Saraswati S, Adolfsen B, Littleton JT. Characterization of the role of the Synaptotagmin family as calcium sensors in facilitation and asynchronous neurotransmitter release. Proc. Natl. Acad. Sci. U.S.A. 2007;104(35):14122–14127
  69. Scheiffele P. Cell-cell signaling during synapse formation in the CNS. Annu. Rev. Neurosci. 2003;26:485–508
  70. Schmidt PJ, Rae TD, Pufahl RA, Hamma T, Strain J, O’Halloran TV, et al. Multiple protein domains contribute to the action of the copper chaperone for superoxide dismutase. J. Biol. Chem. 1999;274(34):23719–23725
  71. Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol. Rev. 2001;81(2):741–766
  72. Selkoe DJ, Schenk D. Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics. Annu. Rev. Pharmacol. Toxicol. 2003;43:545–584
  73. Sinha S, Anderson JP, Barbour R, Basi GS, Caccavello R, Davis D, et al. Purification and cloning of amyloid precursor protein beta-secretase from human brain. Nature. 1999;402(6761):537–540
  74. Small GW, Ercoli LM, Silverman DH, Huang SC, Komo S, Bookheimer SY, et al. Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease. Proc. Natl. Acad. Sci. U.S.A. 2000;97(11):6037–6042
  75. Sollner T, Whiteheart SW, Brunner M, Erdjument-Bromage H, Geromanos S, Tempst P, et al. SNAP receptors implicated in vesicle targeting and fusion. Nature. 1993;362(6418):318–324
  76. Sugita S, Janz R, Sudhof TC. Synaptogyrins regulate Ca2+-dependent exocytosis in PC12 cells. J. Biol. Chem. 1999;274(27):18893–18901
  77. Thal DR, Rub U, Orantes M, Braak H. Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology. 2002;58(12):1791–1800
  78. Vanderklish PW, Bahr BA. The pathogenic activation of calpain: a marker and mediator of cellular toxicity and disease states. Int. J. Exp. Pathol. 2000;81(5):323–339
  79. Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, et al. Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science. 1999;286(5440):735–741
  80. Waites CL, Craig AM, Garner CC. Mechanisms of vertebrate synaptogenesis. Annu. Rev. Neurosci. 2005;28:251–274
  81. Yan R, Bienkowski MJ, Shuck ME, Miao H, Tory MC, Pauley AM, et al. Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity. Nature. 1999;402(6761):533–537
  82. Yan SD, Fu J, Soto C, Chen X, Zhu H, Al-Mohanna F, et al. An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer's disease. Nature. 1997;389(6652):689–695
  83. Zhou W, Scott SA, Shelton SB, Crutcher KA. Cathepsin D-mediated proteolysis of apolipoprotein E: possible role in Alzheimer's disease. Neuroscience. 2006;143(3):689–701

PII: S0197-4580(08)00164-4

doi: 10.1016/j.neurobiolaging.2008.05.013

Neurobiology of Aging
Volume 31, Issue 4 , Pages 549-566 , April 2010

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