Evidence That Synaptically Released β-Amyloid Accumulates as Extracellular Deposits in the Hippocampus of Transgenic Mice
Open accessAbstract
A neuropathological hallmark of Alzheimer's disease is the deposition of amyloid-beta (Abeta) peptides in senile plaques in the hippocampus and cerebral cortex. Abeta is derived from larger integral membrane proteins termed amyloid precursor proteins (APP). We demonstrated previously that APP, synthesized by neurons in the entorhinal cortex, is transported via the perforant pathway to presynaptic terminals in the dentate gyrus. We reported that, although full-length APP and membrane-tethered, C-terminal APP derivatives (APP-CTFs) accumulate at terminal fields, the production of Abeta peptides at these sites was indeterminate. To test the hypothesis that APP-CTFs, generated from axonally transported APP, are further metabolized to Abeta peptides that are subsequently released and deposited proximal to nerve terminals, we created unilateral knife lesions of the perforant pathway of transgenic mice that exhibit hippocampal amyloid deposits. We observed pronounced reductions in amyloid burden in the ipsilateral dentate gyrus, findings that lead us to conclude that axonally transported APP gives rise to Abeta peptides that are released from presynaptic sites in the dentate gyrus and deposited in extracellular plaques. Moreover, our findings are consistent with the view that Abeta deposits are dynamic structures and that the perforant path lesion alters the equilibrium between Abeta production-deposition toward clearance as a consequence of blocked axonal transport of APP from the entorhinal cortex to terminal fields in the hippocampus.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Amyloid beta aggregation usually starts in presynaptic axon terminals, where amyloid precursor protein is transported by vesicles and becomes enriched.
“The Aβ aggregation usually starts in the presynaptic axon terminals, where APP is transported by vesicles and becomes enriched [33, 42, 53].”
From Abnormal accumulation of extracellular vesicles in hippocampal dystrophic axons and regulation by the primary cilia in Alzheimer's disease (2023) · cites this paper as [42]
The Abstract (page unavailable) says APP is transported to presynaptic terminals, where APP and its derivatives accumulate. It concludes that Aβ is released from those sites and deposited in extracellular plaques. It does not establish that Aβ aggregation usually begins inside presynaptic terminals or specify that APP is transported by vesicles; the Discussion (page unavailable) says the origin of the deposited Aβ peptides remains unclear. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMost neuronal amyloid beta is secreted at presynaptic terminals, thus favouring plaque deposition in the grey matter.
“The lower abundance of plaques in the white matter could further be explained by the evidence that most neuronal Aβ is secreted at presynaptic terminals, thus favouring plaque deposition in the grey matter [50,51].”
From Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s disease (2024) · cites this paper as [50]
The Abstract reports that Aβ released from presynaptic sites in the dentate gyrus is deposited in extracellular plaques. The Discussion calls synaptic release a principal contributor to deposition but acknowledges limits to that conclusion. The paper does not establish that most neuronal Aβ is secreted at presynaptic terminals or compare plaque deposition in grey and white matter; page numbers are unavailable in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measuredAmyloid plaque loading is known to be high in the hippocampus.
“Similar to the cortex, amyloid plaque loading is known to be high in hippocampus (Lazarov et al., 2002; Vyas et al., 2020).”
From Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging (2022) · cites this paper as Lazarov et al., 2002
Plaques appear to form from Aβ released at the neuron terminal.
“In addition, plaques appear to form from A 𝛃 released at the neuron terminal (Lazarov et al., 2002; Sheng et al., 2002), considered to be a major site of A 𝛃 generation and secretion.”
From Intraneuronal β-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation (2006) · cites this paper as Lazarov et al., 2002
Amyloid pathology might be gradually transmitted through connected brain structures.
“Some studies have indicated that amyloid pathology might be gradually transmitted through connected brain structures [10, 69, 84, 96], by mechanisms that are still under investigation.”
From Senescence-related impairment of autophagy induces toxic intraneuronal amyloid-β accumulation in a mouse model of amyloid pathology (2023) · cites this paper as [69]
Lesioning the perforant pathway reduces plaque pathology at terminal synaptic fields in the hippocampus.
“Lesioning of the perforant pathway originating in the early AD prone entorhinal cortex leads to reduced plaque pathology at terminal synaptic fields in the hippocampus [96, 171].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [96]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063 · see citing works
Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse
Schenk, D., Barbour, R., Dunn, W., Gordon, G., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., et al. (1999) · Nature · doi:10.1038/22124 · Cited by 3,160 · see citing works
Self-citationScheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M., Suzuki, N., Bird, T. D., Hardy, J., Hutton, M., Kukull, W., et al. (1996) · Nature Medicine · doi:10.1038/nm0896-864 · Cited by 2,599 · see citing works
Profound Loss of Layer II Entorhinal Cortex Neurons Occurs in Very Mild Alzheimer’s Disease
Gómez-Isla, T., Price, J. L., McKeel Jr., D. W., Morris, J. C., Growdon, J. H., & Hyman, B. T. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-14-04491.1996 · Cited by 1,796 · cited 1× · see citing works
“Neuropathological studies have revealed that neurons in the EC and the hippocampus are particularly vulnerable in AD, with abundant amyloid deposition and neurofibrillary pathology in both regions (Van Hoesen et al., 1991; Braak and Braak, 1996; Gomez-Isla et al., 1996).”
BackgroundBorchelt, D. R., Thinakaran, G., Eckman, C. B., Lee, M. K., Davenport, F., Ratovitsky, T., Prada, C.-M., Kim, G., Seekins, S., Yager, D., et al. (1996) · Neuron · doi:10.1016/s0896-6273(00)80230-5 · Cited by 1,478 · see citing works
Self-citationIncreased amyloid-β42(43) in brains of mice expressing mutant presenilin 1
Duff, K., Eckman, C., Zehr, C., Yu, X., Prada, C.-M., Pérez‐Tur, J., Hutton, M., Buée, L., Harigaya, Y., Yager, D., et al. (1996) · Nature · doi:10.1038/383710a0 · Cited by 1,453 · see citing works
Shibata, M., Yamada, S., Kumar, S. R., Calero, M., Bading, J., Frangione, B., Holtzman, D. M., Miller, C. A., Strickland, D. K., Ghiso, J., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10498 · Cited by 1,413 · see citing works
DeMattos, R. B., Bales, K. R., Cummins, D. J., Dodart, J.-C., Paul, S. M., & Holtzman, D. M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151261398 · Cited by 1,298 · see citing works
Citron, M., Westaway, D., Xia, W., Carlson, G., Diehl, T., Levesque, G., Johnson-wood, K., Lee, M., Seubert, P., Davis, A., et al. (1997) · Nature Medicine · doi:10.1038/nm0197-67 · Cited by 1,271 · see citing works
Self-citationBorchelt, D. R., Ratovitski, T., van Lare, J., Lee, M. K., Gonzales, V., Jenkins, N. A., Copeland, N. G., Price, D. L., & Sisodia, S. S. (1997) · Neuron · doi:10.1016/s0896-6273(00)80974-5 · Cited by 1,023 · see citing works
Self-citationHoltzman, D. M., Bales, K. R., Tenkova, T., Fagan, A. M., Parsadanian, M., Sartorius, L. J., Mackey, B., Olney, J., McKeel, D., Wozniak, D., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.050004797 · Cited by 937 · see citing works
Cells of origin of entorhinal cortical afferents to the hippocampus and fascia dentata of the rat
Steward, O., & Scoville, S. A. (1976) · The Journal of Comparative Neurology · doi:10.1002/cne.901690306 · Cited by 837 · see citing works
Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport.
Koo, E. H., Sisodia, S. S., Archer, D. R., Martin, L. J., Weidemann, A., Beyreuther, K., Fischer, P., Masters, C. L., & Price, D. L. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.4.1561 · Cited by 733 · see citing works
Self-citationEvolution of the neuropathology of Alzheimer's disease
Braak, H., & Braak, E. (1996) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.1996.tb05866.x · Cited by 710 · see citing works
Origin and termination of the hippocampal perforant path in the rat studied by silver impregnation
Hjorth‐Simonsen, A., & Jeune, B. (1972) · The Journal of Comparative Neurology · doi:10.1002/cne.901440206 · Cited by 680 · see citing works
IRIZARRY, M. C., MCNAMARA, M., FEDORCHAK, K., HSIAO, K., & HYMAN, B. T. (1997) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199709000-00002 · Cited by 649 · see citing works
Kamal, A., Almenar-Queralt, A., LeBlanc, J. F., Roberts, E. A., & Goldstein, L. S. B. (2001) · Nature · doi:10.1038/414643a · Cited by 583 · see citing works
MUTANT GENES IN FAMILIAL ALZHEIMER'S DISEASE AND TRANSGENIC MODELS
Price, D. L., & Sisodia, S. S. (1998) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.21.1.479 · Cited by 568 · see citing works
Self-citationDeMattos, R. B., Bales, K. R., Cummins, D. J., Paul, S. M., & Holtzman, D. M. (2002) · Science · doi:10.1126/science.1067568 · Cited by 563 · see citing works
Kamal, A., Stokin, G. B., Yang, Z., Xia, C.-H., & Goldstein, L. S. B. (2000) · Neuron · doi:10.1016/s0896-6273(00)00124-0 · Cited by 544 · see citing works
Irizarry, M. C., Soriano, F., McNamara, M., Page, K. J., Schenk, D., Games, D., & Hyman, B. T. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-18-07053.1997 · Cited by 497 · see citing works
Dieck, S., Sanmartí-Vila, L., Langnaese, K., Richter, K., Kindler, S., Soyke, A., Wex, H., Smalla, K.-H., Kämpf, U., Fränzer, J.-T., et al. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.142.2.499 · Cited by 482 · see citing works
Entorhinal cortex pathology in Alzheimer's disease
van Hoesen, G. W., Hyman, B. T., & Damasio, A. R. (1991) · Hippocampus · doi:10.1002/hipo.450010102 · Cited by 475 · see citing works
Assembling the Presynaptic Active Zone
Zhai, R. G., Vardinon-Friedman, H., Cases-Langhoff, C., Becker, B., Gundelfinger, E. D., Ziv, N. E., & Garner, C. C. (2001) · Neuron · doi:10.1016/s0896-6273(01)00185-4 · Cited by 424 · see citing works
Holtzman, D. M., Bales, K. R., Wu, S., Bhat, P., Parsadanian, M., Fagan, A. M., Chang, L. K., Sun, Y., & Paul, S. M. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6179 · Cited by 349 · see citing works
Dickson, T. C., & Vickers, J. C. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00169-5 · Cited by 294 · see citing works
Sisodia, S., Koo, E., Hoffman, P., Perry, G. L., & Price, D. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-07-03136.1993 · Cited by 284 · see citing works
Self-citationKaether, C., Skehel, P., & Dotti, C. G. (2000) · Molecular Biology of the Cell · doi:10.1091/mbc.11.4.1213 · Cited by 270 · see citing works
Buxbaum, J. D., Thinakaran, G., Koliatsos, V. E., O’Callahan, J., Slunt, H. H., Price, D. L., & Sisodia, S. S. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-23-09629.1998 · Cited by 266 · see citing works
Self-citationNarita, M., Holtzman, D. M., Schwartz, A. L., & Bu, G. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69051904.x · Cited by 259 · see citing works
Tamamaki, N., & Nojyo, Y. (1993) · Hippocampus · doi:10.1002/hipo.450030408 · Cited by 216 · see citing works
Turnover of Amyloid β-Protein in Mouse Brain and Acute Reduction of Its Level by Phorbol Ester
Savage, M. J., Trusko, S. P., Howland, D. S., Pinsker, L. R., Mistretta, S., Reaume, A. G., Greenberg, B. D., Siman, R., & Scott, R. W. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-05-01743.1998 · Cited by 213 · see citing works
Aβ-Induced Inflammatory Processes in Microglia Cells of APP23 Transgenic Mice
Bornemann, K. D., Wiederhold, K., Pauli, C., Ermini, F., Stalder, M., Schnell, L., Sommer, B., Jucker, M., & Staufenbiel, M. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63945-4 · Cited by 204 · see citing works
Development of cholinergic innervation in the hippocampal formation of the rat
Matthews, D. A., Nadler, J. V., Lynch, G. S., & Cotman, C. W. (1974) · Developmental Biology · doi:10.1016/0012-1606(74)90196-1 · Cited by 201 · see citing works
Development of cholinergic innervation in the hippocampal formation of the rat
Nadler, J. V., Matthews, D. A., Cotman, C. W., & LYNCH, G. S. (1974) · Developmental Biology · doi:10.1016/0012-1606(74)90197-3 · Cited by 163 · see citing works
Amyloid precursor protein in aged nonhuman primates.
Martin, L. J., Sisodia, S. S., Koo, E. H., Cork, L. C., Dellovade, T., Weidemann, A., Beyreuther, K. T., Masters, C. L., & Price, D. L. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.4.1461 · Cited by 146 · see citing works
Self-citationHyperaccumulation of FAD-linked presenilin 1 variants in vivo
Lee, M. K., Borchelt, D., Kim, G. J., Thinakaran, G., Slunt, H. H., Ratovitski, T., Martin, L. J., Kittur, A., Gandy, S., Levey, A. I., et al. (1997) · Nature Medicine · doi:10.1038/nm0797-756 · Cited by 145 · see citing works
Self-citationIntraneuronal compartments of the amyloid precursor protein
Ferreira, A., Cáceres, A., & Kosik, K. S. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-07-03112.1993 · Cited by 140 · see citing works
Barelli, H., Lebeau, A., Vizzavona, J., Delaère, P., Chevallier, N., Drouot, C., Marambaud, P., Ancolio, K., Buxbaum, J. D., Khorkova, O., et al. (1997) · Molecular Medicine · doi:10.1007/bf03401708 · Cited by 139 · see citing works
Braak, H., Braak, E., & Strothjohann, M. H. (1994) · Neuroscience Letters · doi:10.1016/0304-3940(94)90589-4 · Cited by 138 · see citing works
Sprouting in the hippocampus is layer-specific
Frotscher, M., Heimrich, B., & Deller, T. (1997) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)01018-1 · Cited by 109 · see citing works
Pigino, G. F., Pelsman, A., Mori, H., & Busciglio, J. A. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-03-00834.2001 · Cited by 108 · see citing works
Deposition of ?/A4 protein along neuronal plasma membranes in diffuse senile plaques
Probst, A., Langui, D., Ipsen, S., Robakis, N. K. R. K., & ULRICH, J. (1991) · Acta Neuropathologica · doi:10.1007/bf00294426 · Cited by 105 · see citing works
Vickers, J. C., Chin, D., Edwards, A.-M., Sampson, V., Harper, C. G., & Morrison, J. H. (1996) · Experimental Neurology · doi:10.1006/exnr.1996.0133 · Cited by 86 · see citing works
Steward, O. (1976) · Science · doi:10.1126/science.982024 · Cited by 84 · see citing works
Morphological features of the entorhinal–hippocampal connection
Turner, D. A., Buhl, E. H., Hailer, N. P., & Nitsch, R. (1998) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00019-7 · Cited by 70 · see citing works
Steward, O., & Vinsant, S. L. (1978) · Brain Research · doi:10.1016/0006-8993(78)90837-5 · Cited by 54 · see citing works
Nadler, J. V., Cotman, C. W., Paoletti, C., et al. (1977) · The Journal of Comparative Neurology · doi:10.1002/cne.901710410 · Cited by 51 · see citing works
Amaratunga, A., & Fine, R. E. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.29.17268 · Cited by 44 · see citing works
Garbuglia, M., Verzini, M., Sorci, G., et al. (1999) · Brazilian Journal of Medical and Biological Research · doi:10.1590/s0100-879x1999001000001 · Cited by 44 · see citing works
Dopamine increases glial cell line-derived neurotrophic factor in human fetal astrocytes
Kinor, N., Geffen, R., Golomb, E., Zinman, T., & Yadid, G. (2001) · Glia · doi:10.1002/1098-1136(200102)33:2 · Cited by 32 · see citing works
Transgenic models of neurodegenerative diseases
Lee, M. K., Borchelt, D., Wong, P. C., Sisodia, S. S., & Price, D. L. (1996) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(96)80099-7 · Cited by 29 · see citing works
Self-citationFishman, C. E., Cummins, D. J., Bales, K. R., DeLong, C. A., Esterman, M. A., Hanson, J. C., White, S. L., Paul, S. M., & Jordan, W. H. (2001) · Journal of Neuroscience Methods · doi:10.1016/s0165-0270(01)00381-8 · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Querfurth, H. W., & LaFerla, F. M. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0909142 · Cited by 4,569 · see citing works
Oakley, H., Cole, S. L., Logan, S., Maus, E., Shao, P., Craft, J., Guillozet-Bongaarts, A., Ohno, M., Disterhoft, J., Van Eldik, L., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1202-06.2006 · Cited by 3,530 · see citing works
“In addition, plaques appear to form from A released at the neuron terminal (Lazarov et al., 2002; Sheng et al., 2002), considered to be a major site of A generation and secretion.”
BackgroundPathways towards and Away from Alzheimer’s Disease
Mattson, M. P. (2004) · Nature · doi:10.1038/nature02621 · Cited by 3,052 · see citing works
Synaptic Activity Regulates Interstitial Fluid Amyloid-β Levels In Vivo
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., & Holtzman, D. M. (2005) · Neuron · doi:10.1016/j.neuron.2005.10.028 · Cited by 1,265 · see citing works
Trafficking and Proteolytic Processing of APP
Haass, C., Kaether, C., Thinakaran, G., & Sisodia, S. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006270 · Cited by 1,075 · see citing works
Self-citationNeuronal calcium mishandling and the pathogenesis of Alzheimer's disease
Bezprozvanny, I., & Mattson, M. P. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.06.005 · Cited by 938 · see citing works
Environmental Enrichment Reduces Aβ Levels and Amyloid Deposition in Transgenic Mice
Lazarov, O., Robinson, J., Tang, Y.-P., Hairston, I. S., Korade-Mirnics, Z., Lee, V. M.-Y., Hersh, L. B., Sapolsky, R. M., Mirnics, K., & Sisodia, S. S. (2005) · Cell · doi:10.1016/j.cell.2005.01.015 · Cited by 885 · see citing works
Self-citationNeuronal activity regulates the regional vulnerability to amyloid-β deposition
Bero, A. W., Yan, P., Roh, J. H., Cirrito, J. R., Stewart, F. R., Raichle, M. E., Lee, J.-M., & Holtzman, D. M. (2011) · Nature Neuroscience · doi:10.1038/nn.2801 · Cited by 880 · see citing works
Endocytosis Is Required for Synaptic Activity-Dependent Release of Amyloid-β In Vivo
Cirrito, J. R., Kang, J.-E., Lee, J., Stewart, F. R., Verges, D. K., Silverio, L. M., Bu, G., Mennerick, S., & Holtzman, D. M. (2008) · Neuron · doi:10.1016/j.neuron.2008.02.003 · Cited by 635 · see citing works
Alzheimer's disease as homeostatic responses to age-related myelin breakdown
Bartzokis, G. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.08.007 · Cited by 546 · see citing works
The Alzheimer's disease Beta-secretase enzyme, BACE1
Cole, S. L., & Vassar, R. (2007) · Molecular Neurodegeneration · doi:10.1186/1750-1326-2-22 · Cited by 550 · see citing works
Linking Aβ and Tau in Late-Onset Alzheimer's Disease: A Dual Pathway Hypothesis
Small, S. A., & Duff, K. (2008) · Neuron · doi:10.1016/j.neuron.2008.11.007 · Cited by 546 · see citing works
The Role of NMDA Receptors in Alzheimer’s Disease
Liu, J., Chang, L., Song, Y., Li, H., & Wu, Y. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00043 · Cited by 535 · see citing works
Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease
Depp, C., Sun, T., Sasmita, A. O., Spieth, L., Berghoff, S. A., Nazarenko, T., Overhoff, K., Steixner-Kumar, A. A., Subramanian, S., Arinrad, S., et al. (2023) · Nature · doi:10.1038/s41586-023-06120-6 · Cited by 476 · see citing works
Gowrishankar, S., Yuan, P., Wu, Y., Schrag, M., Paradise, S., Grutzendler, J., De Camilli, P., & Ferguson, S. M. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1510329112 · Cited by 406 · see citing works
Beta-amyloid accumulation in APP mutant neurons reduces PSD-95 and GluR1 in synapses
Almeida, C. G., Tampellini, D., Takahashi, R. H., Greengard, P., Lin, M. T., Snyder, E. M., & Gouras, G. K. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.02.008 · Cited by 397 · see citing works
Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease
Gouras, G. K., Tampellini, D., Takahashi, R. H., & Capetillo-Zarate, E. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0679-9 · Cited by 372 · see citing works
Amyloid beta from axons and dendrites reduces local spine number and plasticity
Wei, W., Nguyen, L. N., Kessels, H. W., Hagiwara, H., Sisodia, S., & Malinow, R. (2010) · Nature Neuroscience · doi:10.1038/nn.2476 · Cited by 357 · see citing works
Self-citationZhao, J., Fu, Y., Yasvoina, M., Shao, P., Hitt, B., O'Connor, T., Logan, S., Maus, E., Citron, M., Berry, R., et al. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4396-06.2007 · Cited by 365 · see citing works
Intraneuronal Aβ accumulation and origin of plaques in Alzheimer's disease
Gouras, G. K., Almeida, C. G., & Takahashi, R. H. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.05.022 · Cited by 338 · see citing works
Harris, J. A., Devidze, N., Verret, L., Ho, K., Halabisky, B., Thwin, M. T., Kim, D., Hamto, P., Lo, I., Yu, G.-Q., et al. (2010) · Neuron · doi:10.1016/j.neuron.2010.10.020 · Cited by 319 · see citing works
Brain deposition of beta-amyloid is a common pathologic feature in HIV positive patients
Green, D. A., Masliah, E., Vinters, H. V., Beizai, P., Moore, D. J., & Achim, C. L. (2005) · AIDS · doi:10.1097/01.aids.0000161770.06158.5c · Cited by 299 · see citing works
Amyloid-β Dynamics Correlate with Neurological Status in the Injured Human Brain
Brody, D. L., Magnoni, S., Schwetye, K. E., Spinner, M. L., Esparza, T. J., Stocchetti, N., Zipfel, G. J., & Holtzman, D. M. (2008) · Science · doi:10.1126/science.1161591 · Cited by 295 · see citing works
A Dynamic Relationship between Intracellular and Extracellular Pools of Aβ
Oddo, S., Caccamo, A., Smith, I. F., Green, K. N., & LaFerla, F. M. (2006) · The American Journal of Pathology · doi:10.2353/ajpath.2006.050593 · Cited by 261 · see citing works
Synaptic Changes in Alzheimer's Disease
Gylys, K. H., Fein, J. A., Yang, F., Wiley, D. J., Miller, C. A., & Cole, G. M. (2004) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63436-0 · Cited by 253 · see citing works
Severely dystrophic axons at amyloid plaques remain continuous and connected to viable cell bodies
Adalbert, R., Nogradi, A., Babetto, E., Janeckova, L., Walker, S. A., Kerschensteiner, M., Misgeld, T., & Coleman, M. P. (2009) · Brain · doi:10.1093/brain/awn312 · Cited by 177 · see citing works
Saura, C. A., Chen, G., Malkani, S., Choi, S.-Y., Takahashi, R. H., Zhang, D., Gouras, G. K., Kirkwood, A., Morris, R. G. M., & Shen, J. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1247-05.2005 · Cited by 157 · see citing works
Yamamoto, M., Horiba, M., Buescher, J. L., Huang, D., Gendelman, H. E., Ransohoff, R. M., & Ikezu, T. (2005) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)62364-4 · Cited by 137 · see citing works
Age-dependent axonal degeneration in an Alzheimer mouse model
Wirths, O., Weis, J., Kayed, R., Saido, T. C., & Bayer, T. A. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.07.021 · Cited by 127 · see citing works
In vivo characterization of the early states of the amyloid-beta network
Sepulcre, J., Sabuncu, M. R., Becker, A., Sperling, R., & Johnson, K. A. (2013) · Brain · doi:10.1093/brain/awt146 · Cited by 117 · see citing works
Microglial large extracellular vesicles propagate early synaptic dysfunction in Alzheimer’s disease
Gabrielli, M., Prada, I., Joshi, P., Falcicchia, C., D’Arrigo, G., Rutigliano, G., Battocchio, E., Zenatelli, R., Tozzi, F., Radeghieri, A., et al. (2022) · Brain · doi:10.1093/brain/awac083 · Cited by 106 · see citing works
Ginsberg, S. D., Elarova, I., Ruben, M., Tan, F., Counts, S. E., Eberwine, J. H., Trojanowski, J. Q., Hemby, S. E., Mufson, E. J., & Che, S. (2004) · Neurochemical Research · doi:10.1023/b:nere.0000023593.77052.f7 · Cited by 97 · see citing works
Axonal transport of APP and the spatial regulation of APP cleavage and function in neuronal cells
Brunholz, S., Sisodia, S., Lorenzo, A., Deyts, C., Kins, S., & Morfini, G. (2012) · Experimental Brain Research · doi:10.1007/s00221-011-2870-1 · Cited by 92 · see citing works
Self-citationCai, W., Li, L., Sang, S., Pan, X., & Zhong, C. (2023) · Neuroscience Bulletin · doi:10.1007/s12264-022-00985-9 · Cited by 83 · see citing works
Inhibition of APP Trafficking by Tau Protein Does Not Increase the Generation of Amyloid‐β Peptides
Goldsbury, C., Mocanu, M., Thies, E., Kaether, C., Haass, C., Keller, P., Biernat, J., Mandelkow, E., & Mandelkow, E. (2006) · Traffic · doi:10.1111/j.1600-0854.2006.00434.x · Cited by 82 · see citing works
Zhong, P., Gu, Z., Wang, X., Jiang, H., Feng, J., & Yan, Z. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302789200 · Cited by 71 · see citing works
Rajani, R. M., Ellingford, R., Hellmuth, M., Harris, S. S., Taso, O. S., Graykowski, D., Lam, F. K. W., Arber, C., Fertan, E., Danial, J. S. H., et al. (2024) · PLOS Biology · doi:10.1371/journal.pbio.3002727 · Cited by 57 · see citing works
“The lower abundance of plaques in the white matter could further be explained by the evidence that most neuronal A β is secreted at presynaptic terminals, thus favouring plaque deposition in the grey matter [50,51].”
BackgroundNiederst, E. D., Reyna, S. M., & Goldstein, L. S. B. (2015) · Molecular Biology of the Cell · doi:10.1091/mbc.e14-06-1049 · Cited by 51 · see citing works
Etiology of type 2 diabetes and Alzheimer’s disease: Exploring the mitochondria
Silzer, T. K., & Phillips, N. R. (2018) · Mitochondrion · doi:10.1016/j.mito.2018.04.004 · Cited by 53 · see citing works
Suelves, N., Saleki, S., Ibrahim, T., Palomares, D., Moonen, S., Koper, M. J., Vrancx, C., Vadukul, D. M., Papadopoulos, N., Viceconte, N., et al. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01578-x · Cited by 43 · see citing works
Jana, A., Wang, X., Leasure, J. W., Magana, L., Wang, L., Kim, Y.-M., Dodiya, H., Toth, P. T., Sisodia, S. S., & Rehman, J. (2022) · Scientific Reports · doi:10.1038/s41598-022-20889-y · Cited by 43 · see citing works
Self-citationBeta-amyloid short- and long-term synaptic entanglement
Lanni, C., Fagiani, F., Racchi, M., Preda, S., Pascale, A., Grilli, M., Allegri, N., & Govoni, S. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2018.11.018 · Cited by 29 · see citing works
George, S., Rönnbäck, A., Gouras, G. K., Petit, G. H., Grueninger, F., Winblad, B., Graff, C., & Brundin, P. (2014) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-2-17 · Cited by 23 · see citing works
Jang, J., Yeo, S., Baek, S., Jung, H. J., Lee, M. S., Choi, S. H., & Choe, Y. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01637-3 · Cited by 20 · see citing works
“The Aβ aggregation usually starts in the presynaptic axon terminals, where APP is transported by vesicles and becomes enriched [33, 42, 53].”
BackgroundSelf-citationGenetic and pharmacological evidence of intraneuronal Aβ accumulation in APP transgenic mice
Philipson, O., Lannfelt, L., & Nilsson, L. N. G. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.08.009 · Cited by 21 · see citing works
Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging
Maharjan, S., Tsai, A. P., Lin, P. B., Ingraham, C., Jewett, M. R., Landreth, G. E., Oblak, A. L., & Wang, N. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.964654 · Cited by 11 · see citing works
“Similar to the cortex, amyloid plaque loading is known to be high in hippocampus (Lazarov et al., 2002; Vyas et al., 2020).”
Background
- Authors
- Lazarov, O., Lee, M., Peterson, D. A., & Sisodia, S. S.
- Affiliations
- University of Chicago (US)
- Johns Hopkins University (US)
- Rosalind Franklin University of Medicine and Science (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2002-11-15
- Volume
- 22
- Issue
- 22
- Pages
- 9785-9793
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6757836
- OpenAlex
- W1955491145
- Cited by
- 302
- References
- 53
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 4 · 2023: 6 · 2022: 9 · 2021: 10 · 2020: 7 · 2019: 5 · 2018: 8 · 2017: 10 · 2016: 10 · 2015: 14 · 2014: 16 · 2013: 15 · 2012: 13
- FWCI
- 9.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ellison Medical Foundation
- National Institutes of Health
- National Institute on Aging (AG-20047-02, R01AG021494, AG-021494, R01AG020047)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- amyloid-beta, Alzheimer's disease, amyloid precursor protein, axonal transport, perforant path, dentate gyrus, entorhinal cortex, presynaptic terminals, extracellular amyloid deposition, amyloid plaques, transgenic mice, amyloid-beta clearance
- MeSH terms
- Alzheimer Disease, Animals, Axonal Transport, Disease Models, Animal, Extracellular Space, Gliosis, Hippocampus, Humans, Mice, Transgenic, Stereotaxic Techniques, Synapses, Amyloid beta-Peptides, Neurites, Amyloid beta-Protein Precursor, Dentate Gyrus, Perforant Pathway, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
