Synaptic contact number and size in stratum radiatum CA1 of APP/PS1ΔE9 transgenic mice

Neurobiology of Aging

Volumn 30, Issue 11, 2009, Pages 1756-1776

  West, Mark J ^a   Bach, Georg ^a   Søderman, Andreas ^a   Jensen, Jens Ledet ^a  

^a AARHUS UNIVERSITY   (Denmark)

Author keywords

Alzheimer's; Amyloid; APP; Disector; Hippocampus; Stereology; Synapses; Transgenic

Indexed keywords

AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA PROTEIN[1-42];

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN ATROPHY; BRAIN REGION; CONTROLLED STUDY; ELECTRON MICROSCOPY; FEMALE; HIPPOCAMPUS; HIPPOCAMPUS PYRAMIDAL CELL LAYER; IMMUNOHISTOCHEMISTRY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PYRAMIDAL NERVE CELL; RIGHT HEMISPHERE; STEREOLOGY; SYNAPSE; TRANSGENIC MOUSE; WILD TYPE;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; ATROPHY; CA1 REGION, HIPPOCAMPAL; CELL COUNT; CEREBRAL CORTEX; DISEASE MODELS, ANIMAL; FEMALE; HUMANS; MICE; MICE, TRANSGENIC; NEURONS; PLAQUE, AMYLOID; PRESENILIN-1; STEREOTAXIC TECHNIQUES; SYNAPSES;

EID: 70049087978     PISSN: 01974580     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.neurobiolaging.2008.01.009     Document Type: Article

References (115)

1. Almeida C.G., Tampellini D., Takahashi R.H., Greengard P., Lin M.T., Snyder E.M., and Gouras G.K. Beta-amyloid accumulation in APP mutant neurons reduces PSD-95 and GluR1 in synapses. Neurobiol. Dis. 20 2 (2005) 187-198
2. Ashley J., Packard M., Ataman B., and Budnik V. Fasciclin II signals new synapse formation through amyloid precursor protein and the scaffolding protein dX11/Mint. J. Neurosci. 25 25 (2005) 5943-5955
3. Barndorff-Nielsen O. Exponentially decreasing distributions for the logarithm of particle size. Proc. Roy. Soc. Lond. A 353 (1977) 401-419
4. Bell K.F.S., and Cuello A.C. Altered synaptic function in Alzheimers disease. Eur. J. Pharmacol. 545 (2006) 11-21
5. Blæsild, P., Sørensen, M.K., 1992. Letter to Anonymous.
6. Blanchard V., Moussaoui S., Czech C., Touchet N., Bonici B., Planche M., Canton T., Jedidi I., Gohin M., Wirths O., Bayer T.A., Langui D., Duyckaerts C., Tremp G., and Pradier L. Time sequence of maturation of dystrophic neurites associated with Abeta deposits in APP/PS1 transgenic mice. Exp. Neurol. 184 1 (2003) 247-263
7. Boncristiano S., Calhoun M.E., Howard V., Bondolfi L., Kaeser S.A., Wiederhold K.H., Staufenbiel M., and Jucker M. Neocortical synaptic bouton number is maintained despite robust amyloid deposition in APP23 transgenic mice. Neurobiol. Aging 26 5 (2005) 607-613
8. Borchelt D.R., Thinakaran G., Eckman C.B., Lee M.K., Davenport F., Ratovitsky T., Prada C.M., Kim G., Seekins S., Yager D., Slunt H.H., Wang R., Seeger M., Levey A.I., Gandy S.E., Copeland N.G., Jenkins N.A., Price D.L., Younkin S.G., and Sisodia S.S. Familial Alzheimer's disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo. Neuron 17 5 (1996) 1005-1013
9. Casas C., Sergeant N., Itier J.M., Blanchard V., Wirths O., van der K.N., Vingtdeux V., van de S.E., Ret G., Canton T., Drobecq H., Clark A., Bonici B., Delacourte A., Benavides J., Schmitz C., Tremp G., Bayer T.A., Benoit P., and Pradier L. Massive CA1/2 neuronal loss with intraneuronal and N-terminal truncated Abeta42 accumulation in a novel Alzheimer transgenic model. Am. J. Pathol. 165 4 (2004) 1289-1300
10. Cirrito J.R., Yamada K.A., Finn M.B., Sloviter R.S., Bales K.R., May P.C., Schoepp D.D., Paul S.M., Mennerick S., and Holtzman D.M. Synaptic activity regulates interstitial fluid amyloid-beta levels in vivo. Neuron 48 6 (2005) 913-922
11. Coleman P., Federoff H., and Kurlan R. A focus on the synapse for neuroprotection in Alzheimer disease and other dementias. Neurology 63 7 (2004) 1155-1162
12. Coleman P.D., and Yao P.J. Synaptic slaughter in Alzheimer's disease. Neurobiol. Aging 24 8 (2003) 1023-1027
13. Cruz-Orive L.M. A general variance predictor for Cavalieri slices. J. Microsc. 222 Pt 3 (2006) 158-165
14. DeGroot D.M.G. Comparison of methods for estimation of the thickness of ultrathin tissue sections. J. Microsc. 151 (1988) 23-42
15. Dickey C.A., Loring J.F., Montgomery J., Gordon M.N., Eastman P.S., and Morgan D. Selectively reduced expression of synaptic plasticity-related genes in amyloid precursor protein + presenilin-1 transgenic mice. J. Neurosci. 23 12 (2003) 5219-5226
16. Dickson D.W. Building a more perfect beast: APP transgenic mice with neuronal loss. Am. J. Pathol. 164 4 (2004) 1143-1146
17. Dong H., Martin M.V., Chambers S., and Csernansky J.G. Spatial relationship between synapse loss and beta-amyloid deposition in Tg2576 mice. J. Comp. Neurol. 500 2 (2007) 311-321
18. Ertekin-Taner N., Ronald J., Feuk L., Prince J., Tucker M., Younkin L., Hella M., Jain S., Hackett A., Scanlin L., Kelly J., Kihiko-Ehman M., Neltner M., Hersh L., Kindy M., Markesbery W., Hutton M., de A.M., Petersen R.C., Graff-Radford N., Estus S., Brookes A.J., and Younkin S.G. Elevated amyloid beta protein (Abeta42) and late onset Alzheimer's disease are associated with single nucleotide polymorphisms in the urokinase-type plasminogen activator gene. Hum. Mol. Genet. 14 3 (2005) 447-460
19. Ferreiro E., Resende R., Costa R., Oliveira C.R., and Pereira C.M. An endoplasmic-reticulum-specific apoptotic pathway is involved in prion and amyloid-beta peptides neurotoxicity. Neurobiol. Dis. 23 3 (2006) 669-678
20. Fiala J.C., and Harris K.M. Cylindrical diameters method for calibrating section thickness in serial electron microscopy. J. Microsc. 202 Pt 3 (2001) 468-472
21. Fiala J.C., and Harris K.M. Extending unbiased stereology of brain ultrastructure to three-dimensional volumes. J. Am. Med. Inform. Assoc. 8 1 (2001) 1-16
22. Forero D.A., Casadesus G., Perry G., and Arboleda H. Synaptic dysfunction and oxidative stress in Alzheimer's disease: emerging mechanisms. J. Cell. Mol. Med. 10 3 (2006) 796-805
23. Ganeshina O., Berry R.W., Petralia R.S., Nicholson D.A., and Geinisman Y. Differences in the expression of AMPA and NMDA receptors between axospinous perforated and nonperforated synapses are related to the configuration and size of postsynaptic densities. J. Comp. Neurol. 468 1 (2004) 86-95
24. Ganeshina O., Berry R.W., Petralia R.S., Nicholson D.A., and Geinisman Y. Synapses with a segmented, completely partitioned postsynaptic density express more AMPA receptors than other axospinous synaptic junctions. Neuroscience 125 3 (2004) 615-623
25. Geinisman Y., Ganeshina O., Yoshida R., Berry R.W., Disteroft J.F., and Gallager M. Aging, spatial learning, and total synapse number in the rat CA1 stratum radiatum. Neurobiol. Aging 25 (2007) 407-416
26. Geinisman Y., Gundersen H.J., van der Z.E., and West M.J. Unbiased stereological estimation of the total number of synapses in a brain region. J. Neurocytol. 25 12 (1996) 805-819
27. Glabe C.G. Common mechanisms of amyloid oligomer pathogenesis in degenerative disease. Neurobiol. Aging 27 4 (2006) 570-575
28. Graff-Radford N.R., Crook J.E., Lucas J., Boeve B.F., Knopman D.S., Ivnik R.J., Smith G.E., Younkin L.H., Petersen R.C., and Younkin S.G. Association of low plasma Abeta42/Abeta40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease. Arch. Neurol. 64 3 (2007) 354-362
29. Grutzendler J., Helmin K., Tsai J., and Gan W.B. Various dendritic abnormalities are associated with fibrillar amyloid deposits in Alzheimer's disease. Ann. NY Acad. Sci. 1097 (2007) 30-39
30. Gundersen H.J. Stereology of arbitrary particles. A review of unbiased number and size estimators and the presentation of some new ones. J. Microsc. 143 (1986) 3-45
31. Gundersen H.J., Jensen E.B., Kieu K., and Nielsen J. The efficiency of systematic sampling in stereology-reconsidered. J. Microsc. 193 Pt 3 (1999) 199-211
32. Haass C., and Selkoe D.J. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat. Rev. Mol. Cell. Biol. 8 2 (2007) 101-112
33. Hardy J.A., and Higgins G.A. Alzheimer's disease: the amyloid cascade hypothesis. Science 256 5054 (1992) 184-185
34. Harris K.M., Perry E., Bourne J., Feinberg M., Ostroff L., and Hurlburt J. Uniform serial sectioning for transmission electron microscopy. J. Neurosci. 26 47 (2006) 12101-12103
35. Hayat M.A. Principles and Techniques of Electron Microscopy, Biological Applications (1970), Van Nostrand Reinhold, New York
36. Herard A.S., Besret L., Dubois A., Dauguet J., Delzescaux T., Hantraye P., Bonvento G., and Moya K.L. siRNA targeted against amyloid precursor protein impairs synaptic activity in vivo. Neurobiol. Aging 27 12 (2006) 1740-1750
37. Hsia A.Y., Masliah E., McConlogue L., Yu G.Q., Tatsuno G., Hu K., Kholodenko D., Malenka R.C., Nicoll R.A., and Mucke L. Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. Proc. Natl. Acad. Sci. U.S.A. 96 6 (1999) 3228-3233
38. Hsieh H., Boehm J., Sato C., Iwatsubo T., Tomita T., Sisodia S., and Malinow R. AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss. Neuron 52 5 (2006) 831-843
39. Iacono, D., O'Brian, R., Resnik, S.M., Zonderman, A.B., Pletnikova, O., Rudow, G., West, M.J., Crain, B., Troncoso, J., submitted for publication. Neuronal hypertrophy in asymptomatic Alzheimer's disease.
40. Iwatsubo T., Odaka A., Suzuki N., Mizusawa H., Nukina N., and Ihara Y. Visualization of Abeta42(43) and Abeta40 in senile plaques with end-specific Abeta monoclonals: evidence that an initially deposited species is Abeta 42(43). Neuron 13 (1994) 45-53
41. Jacobsen J.S., Wu C.C., Redwine J.M., Comery T.A., Arias R., Bowlby M., Martone R., Morrison J.H., Pangalos M.N., Reinhart P.H., and Bloom F.E. Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer's disease. Proc. Natl. Acad. Sci. U.S.A. 103 13 (2006) 5161-5166
42. Jankowsky J.L., Fadale D.J., Anderson J., Xu G.M., Gonzales V., Jenkins N.A., Copeland N.G., Lee M.K., Younkin L.H., Wagner S.L., Younkin S.G., and Borchelt D.R. Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum. Mol. Genet. 13 2 (2004) 159-170
43. Jankowsky J.L., Slunt H.H., Ratovitski T., Jenkins N.A., Copeland N.G., and Borchelt D.R. Co-expression of multiple transgenes in mouse CNS: a comparison of strategies. Biomol. Eng. 17 6 (2001) 157-165
44. Kamenetz F., Tomita T., Hsieh H., Seabrook G., Borchelt D., Iwatsubo T., Sisodia S., and Malinow R. APP processing and synaptic function. Neuron 37 6 (2003) 925-937
45. Kayed R., Head E., Thompson J.L., McIntire T.M., Milton S.C., Cotman C.W., and Glabe C.G. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 300 5618 (2003) 486-489
46. Kelly B.L., and Ferreira A. Beta-amyloid disrupted synaptic vesicle endocytosis in cultured hippocampal neurons. Neuroscience 147 (2007) 60-70
47. Kim J., Onstead L., Randle S., Price R., Smithson L., Zwizinski C., Dickson D.W., Golde T., and McGowan E. Abeta40 inhibits amyloid deposition in vivo. J. Neurosci. 27 3 (2007) 627-633
48. Lacor P.N., Buniel M.C., Furlow P.W., Clemente A.S., Velasco P.T., Wood M., Viola K.L., and Klein W.L. Abeta oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer's disease. J. Neurosci. 27 4 (2007) 796-807
49. Lesne S., Koh M.T., Kotilinek L., Kayed R., Glabe C.G., Yang A., Gallagher M., and Ashe K.H. A specific amyloid-beta protein assembly in the brain impairs memory. Nature 440 7082 (2006) 352-357
50. Machova E., Jakubik J., Michal P., Oksman M., Iivonen H., Tanila H., and Dolezal V. Impairment of muscarinic transmission in transgenic APPswe/PS1dE9 mice. Neurobiol. Aging (2006)
51. Marchesi V.T. An alternative interpretation of the amyloid Abeta hypothesis with regard to the pathogenesis of Alzheimer's disease. Proc. Natl. Acad. Sci. U.S.A. 102 26 (2005) 9093-9098
52. Masliah E., Crews L., and Hansen L. Synaptic remodeling during aging and in Alzheimer's disease. J. Alzheimers Dis. 9 3 Suppl. (2006) 91-99
53. Masliah E., Sisk A., Mallory M., Mucke L., Schenk D., and Games D. Comparison of neurodegenerative pathology in transgenic mice overexpressing V717F beta-amyloid precursor protein and Alzheimer's disease. J. Neurosci. 16 18 (1996) 5795-5811
54. Masliah E., Westland C.E., Rockenstein E.M., Abraham C.R., Mallory M., Veinberg I., Sheldon E., and Mucke L. Amyloid precursor proteins protect neurons of transgenic mice against acute and chronic excitotoxic injuries in vivo. Neuroscience 78 1 (1997) 135-146
55. Mattfeldt T. Editorial introduction to papers. J. Microsc. 222 (2006) 143-145
56. Mattfeldt T. Prediction of the variance of stereological volume estimates from systematic sections using computer-intensive methods. J. Microsc. 222 Pt 3 (2006) 166-176
57. Mattson M.P. Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives. Physiol. Rev. 77 4 (1997) 1081-1132
58. McGowan E., Eriksen J., and Hutton M. A decade of modeling Alzheimer's disease in transgenic mice. Trends Genet. 22 5 (2006) 281-289
59. Micheva K.D., and Smith S.J. Array tomography: a new tool for imaging the molecular architecture and ultrastructure of neural circuits. Neuron 55 1 (2007) 25-36
60. Moolman D.L., Vitolo O.V., Vonsattel J.P., and Shelanski M.L. Dendrite and dendritic spine alterations in Alzheimer models. J. Neurocytol. 33 3 (2004) 377-387
61. Mucke L., Masliah E., Johnson W.B., Ruppe M.D., Alford M., Rockenstein E.M., Forss-Petter S., Pietropaolo M., Mallory M., and Abraham C.R. Synaptotrophic effects of human amyloid beta protein precursors in the cortex of transgenic mice. Brain Res. 666 2 (1994) 151-167
62. Mucke L., Masliah E., Yu G.Q., Mallory M., Rockenstein E.M., Tatsuno G., Hu K., Kholodenko D., Johnson-Wood K., and McConlogue L. High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J. Neurosci. 20 11 (2000) 4050-4058
63. Naruse S., Thinakaran G., Luo J.J., Kusiak J.W., Tomita T., Iwatsubo T., Qian X., Ginty D.D., Price D.L., Borchelt D.R., Wong P.C., and Sisodia S.S. Effects of PS1 deficiency on membrane protein trafficking in neurons. Neuron 21 5 (1998) 1213-1221
64. Nicholson D.A., Yoshida R., Berry R.W., Gallagher M., and Geinisman Y. Reduction in size of perforated postsynaptic densities in hippocampal axospinous synapses and age-related spatial learning impairments. J. Neurosci. 24 35 (2004) 7648-7653
65. Nyengaard J.R., and Gundersen H.J. Direct and efficient stereological estimation of total cell quantities using electron microscopy. J. Microsc. 222 Pt 3 (2006) 182-187
66. Oddo S., Caccamo A., Smith I.F., Green K.N., and LaFerla F.M. A dynamic relationship between intracellular and extracellular pools of Abeta. Am. J. Pathol. 168 1 (2006) 184-194
67. Oh E.S., Savonenko A.V., King J.F., Tucker S.M.F., Rudow G.L., Xu G., Borchelt D., and Troncoso J. Amyloid precurser protein increases cortical neuron size in transgenic mice. Neurobiol. Aging. 30 (2009) 1238-1244
68. Palop J.J., Chin J., Bien-Ly N., Massaro C., Yeung B.Z., Yu G.Q., and Mucke L. Vulnerability of dentate granule cells to disruption of arc expression in human amyloid precursor protein transgenic mice. J. Neurosci. 25 42 (2005) 9686-9693
69. Palop J.J., Chin J., and Mucke L. A network dysfunction perspective on neurodegenerative diseases. Nature 443 7113 (2006) 768-773
70. Perez S.E., Lazarov O., Koprich J.B., Chen E.Y., Rodriguez-Menendez V., Lipton J.W., Sisodia S.S., and Mufson E.J. Nigrostriatal dysfunction in familial Alzheimer's disease-linked APPswe/PS1DeltaE9 transgenic mice. J. Neurosci. 25 44 (2005) 10220-10229
71. Priller C., Dewachter I., Vassallo N., Paluch S., Pace C., Kretzschmar H.A., Van L.F., and Herms J. Mutant presenilin 1 alters synaptic transmission in cultured hippocampal neurons. J. Biol. Chem. 282 2 (2007) 1119-1127
72. Redwine J.M., Kosofsky B., Jacobs R.E., Games D., Reilly J.F., Morrison J.H., Young W.G., and Bloom F.E. Dentate gyrus volume is reduced before onset of plaque formation in PDAPP mice: a magnetic resonance microscopy and stereologic analysis. Proc. Natl. Acad. Sci. U.S.A. 100 3 (2003) 1381-1386
73. Roch J.M., Masliah E., Roch-Levecq A.C., Sundsmo M.P., Otero D.A., Veinbergs I., and Saitoh T. Increase of synaptic density and memory retention by a peptide representing the trophic domain of the amyloid beta/A4 protein precursor. Proc. Natl. Acad. Sci. U.S.A. 91 16 (1994) 7450-7454
74. Roher A.E., Lowenson J.D., Clarke S., Wolkow C., Wang R., Cotter R.J., Reardon I.M., Zurcher-Neely H.A., Heinrikson R.L., and Ball M.J. Structural alterations in the peptide backbone of beta-amyloid core protein may account for its deposition and stability in Alzheimer's disease. J. Biol. Chem. 268 5 (1993) 3072-3083
75. Roselli F., Tirard M., Lu J., Hutzler P., Lamberti P., Livrea P., Morabito M., and Almeida O.F. Soluble beta-amyloid1-40 induces NMDA-dependent degradation of postsynaptic density-95 at glutamatergic synapses. J. Neurosci. 25 48 (2005) 11061-11070
76. Rutten B.P., Van der Kolk N.M., Schafer S., van Zandvoort M.A., Bayer T.A., Steinbusch H.W., and Schmitz C. Age-related loss of synaptophysin immunoreactive presynaptic boutons within the hippocampus of APP751SL, PS1M146L, and APP751SL/PS1M146L transgenic mice. Am. J. Pathol. 167 1 (2005) 161-173
77. Saido T.C., and Iwata N. Metabolism of amyloid beta peptide and pathogenesis of Alzheimer's disease. Towards presymptomatic diagnosis, prevention and therapy. Neurosci. Res. 54 4 (2006) 235-253
78. Salehi A., Delcroix J.D., Belichenko P.V., Zhan K., Wu C., Valletta J.S., Takimoto-Kimura R., Kleschevnikov A.M., Sambamurti K., Chung P.P., Xia W., Villar A., Campbell W.A., Kulnane L.S., Nixon R.A., Lamb B.T., Epstein C.J., Stokin G.B., Goldstein L.S., and Mobley W.C. Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration. Neuron 51 1 (2006) 29-42
79. Scheff S.W., and Price D.A. Synaptic pathology in Alzheimer's disease: a review of ultrastructural studies. Neurobiol. Aging 24 8 (2003) 1029-1046
80. Scheff S.W., Price D.A., Schmitt F.A., DeKosky S.T., and Mufson E.J. Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment. Neurology 68 18 (2007) 1501-1508
81. Scheff S.W., Price D.A., Schmitt F.A., and Mufson E.J. Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment. Neurobiol. Aging 27 10 (2006) 1372-1384
82. Schmitz C., Rutten B.P., Pielen A., Schafer S., Wirths O., Tremp G., Czech C., Blanchard V., Multhaup G., Rezaie P., Korr H., Steinbusch H.W., Pradier L., and Bayer T.A. Hippocampal neuron loss exceeds amyloid plaque load in a transgenic mouse model of Alzheimer's disease. Am. J. Pathol. 164 4 (2004) 1495-1502
83. Selkoe D.J. Alzheimer's disease is a synaptic failure. Science 298 5594 (2002) 789-791
84. Shen J., and Kelleher III R.J. The presenilin hypothesis of Alzheimer's disease: evidence for a loss-of-function pathogenic mechanism. Proc. Natl. Acad. Sci. U.S.A. 104 2 (2007) 403-409
85. Shoji M., and Kanai M. Cerebrospinal fluid Abeta40 and Abeta42: natural course and clinical usefulness. J. Alzheimers Dis. 3 3 (2001) 313-321
86. Sizova D., Charbaut E., Delalande F., Poirier F., High A.A., Parker F., Van D.A., Duchesne M., and Diu-Hercend A. Proteomic analysis of brain tissue from an Alzheimer's disease mouse model by two-dimensional difference gel electrophoresis. Neurobiol. Aging 28 3 (2007) 357-370
87. Slomianka L., and West M.J. Estimators of the precision of stereological estimates: an example based on the CA1 pyramidal cell layer of rats. Neuroscience 136 3 (2005) 757-767
88. Smith I.F., Green K.N., and LaFerla F.M. Calcium dysregulation in Alzheimer's disease: recent advances gained from genetically modified animals. Cell Calcium 38 3/4 (2005) 427-437
89. Snyder E.M., Nong Y., Almeida C.G., Paul S., Moran T., Choi E.Y., Nairn A.C., Salter M.W., Lombroso P.J., Gouras G.K., and Greengard P. Regulation of NMD A receptor trafficking by amyloid-beta. Nat. Neurosci. 8 8 (2005) 1051-1058
90. Spires T.L., and Hyman B.T. Transgenic models of Alzheimer's disease: learning from animals. NeuroRx 2 3 (2005) 423-437
91. Spires T.L., Meyer-Luehmann M., Stern E.A., McLean P.J., Skoch J., Nguyen P.T., Bacskai B.J., and Hyman B.T. Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy. J. Neurosci. 25 31 (2005) 7278-7287
92. Stein T.D., and Johnson J.A. Lack of neurodegeneration in transgenic mice overexpressing mutant amyloid precursor protein is associated with increased levels of transthyretin and the activation of cell survival pathways. J. Neurosci. 22 17 (2002) 7380-7388
93. Stokin G.B., Lillo C., Falzone T.L., Brusch R.G., Rockenstein E., Mount S.L., Raman R., Davies P., Masliah E., Williams D.S., and Goldstein L.S. Axonopathy and transport deficits early in the pathogenesis of Alzheimer's disease. Science 307 5713 (2005) 1282-1288
94. Sultana R., Boyd-Kimball D., Cai J., Pierce W.M., Klein J.B., Merchant M., and Butterfield D.A. Proteomics analysis of the Alzheimer's disease hippocampal proteome. J. Alzheimer's Dis. 11 (2007) 153-164
95. Takeuchi A., Irizarry M.C., Duff K., Saido T.C., Hsiao A.K., Hasegawa M., Mann D.M., Hyman B.T., and Iwatsubo T. Age-related amyloid beta deposition in transgenic mice overexpressing both Alzheimer mutant presenilin 1 and amyloid beta precursor protein Swedish mutant is not associated with global neuronal loss. Am. J. Pathol. 157 1 (2000) 331-339
96. Tang Y., Nyengaard J.R., De Groot D.M., and Gundersen H.J. Total regional and global number of synapses in the human brain neocortex. Synapse 41 3 (2001) 258-273
97. Tanzi R.E. The synaptic Abeta hypothesis of Alzheimer disease. Nat. Neurosci. 8 8 (2005) 977-979
98. Tanzi R.E., and Bertram L. Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective. Cell 120 4 (2005) 545-555
99. Terry R.D., Masliah E., Salmon D.P., Butters N., DeTeresa R., Hansen L.A., and Katzman R. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Annu. Rev. Physiol. 30 (1991) 572-580
100. Teter B., and Ashford J.W. Neuroplasticity in Alzheimer's disease. J. Neurosci. Res. 70 3 (2002) 402-437
101. Thinakaran G., Borchelt D.R., Lee M.K., Slunt H.H., Spitzer L., Kim G., Ratovitsky T., Davenport F., Nordstedt C., Seeger M., Hardy J., Levey A.I., Gandy S.E., Jenkins N.A., Copeland N.G., Price D.L., and Sisodia S.S. Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron 17 1 (1996) 181-190
102. Thinakaran G., Sisodia S.S., and Presenilins. Alzheimer disease: the calcium conspiracy. Nat. Neurosci. 9 11 (2006) 1354-1355
103. Torroja L., Packard M., Gorczyca M., White K., and Budnik V. The Drosophila beta-amyloid precursor protein homolog promotes synapse differentiation at the neuromuscular junction. J. Neurosci. 19 18 (1999) 7793-7803
104. Tu H., Nelson O., Bezprozvanny A., Wang Z., Lee S.F., Hao Y.H., Serneels L., De S.B., Yu G., and Bezprozvanny I. Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer's disease-linked mutations. Cell 126 5 (2006) 981-993
105. van Groen T., Kiliaan A.J., and Kadish I. Deposition of mouse amyloid beta in human APP/PS1 double and single AD model transgenic mice. Neurobiol. Dis. 23 3 (2006) 653-662
106. Vanhecke D., Studer D., and Ochs M. Stereology meets electron tomography: towards quantitative 3D electron microscopy. J. Struct. Biol. 159 3 (2007) 443-450
107. Verret L., Jankowsky J.L., Xu G.M., Borchelt D.R., and Rampon C. Alzheimer's-type amyloidosis in transgenic mice impairs survival of newborn neurons derived from adult hippocampal neurogenesis. J. Neurosci. 27 (2007) 6771-6780
108. West M.J. New stereological methods for counting neurons. Neurobiol. Aging 14 4 (1993) 275-285
109. West M.J. Stereological methods for estimating the total number of neurons and synapses: issues of precision and bias. Trends Neurosci. 22 2 (1999) 51-61
110. West M.J., Coleman P.D., Flood D.G., and Troncoso J.C. Differences in the pattern of neuronal loss in normal aging and Alzheimer's disease. Lancet 244 (1994) 769-772
111. West M.J., Kawas C.H., Stewart W.F., Rudow G.L., and Troncoso J.C. Hippocampal neurons in pre-clinical Alzheimer's disease. Neurobiol. Aging 25 9 (2004) 1205-1212
112. West M.J., Slomianka L., and Gundersen H.J.G. Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator. Anat. Rec. 231 (1991) 482-497
113. Wirths O., Multhaup G., Czech C., Blanchard V., Moussaoui S., Tremp G., Pradier L., Beyreuther K., and Bayer T.A. Intraneuronal Abeta accumulation precedes plaque formation in beta-amyloid precursor protein and presenilin-1 double-transgenic mice. Neurosci. Lett. 306 1/2 (2001) 116-120
114. Wirths O., Weis J., Kayed R., Saido T.C., and Bayer T.A. Age-dependent axonal degeneration in an Alzheimer mouse model. Neurobiol. Aging 28 (2007) 1689-1699
115. Witgen B.M., Grady M.S., Nyengaard J.R., and Gundersen H.J. A new fractionator principle with varying sampling fractions: exemplified by estimation of synapse number using electron microscopy. J. Microsc. 222 Pt 3 (2006) 251-255