The PI3K-Akt-mTOR pathway regulates Aβ oligomer induced neuronal cell cycle events
Open accessAbstract
Accumulating evidence suggests that neurons prone to degeneration in Alzheimer's Disease (AD) exhibit evidence of re-entry into an aberrant mitotic cell cycle. Our laboratory recently demonstrated that, in a genomic amyloid precursor protein ( APP ) mouse model of AD (R1.40), neuronal cell cycle events (CCEs) occur in the absence of beta-amyloid (Aβ) deposition and are still dependent upon the amyloidogenic processing of the amyloid precursor protein (APP). These data suggested that soluble Aβ species might play a direct role in the induction of neuronal CCEs. Here, we show that exposure of non-transgenic primary cortical neurons to Aβ oligomers, but not monomers or fibrils, results in the retraction of neuronal processes, and induction of CCEs in a concentration dependent manner. Retraction of neuronal processes correlated with the induction of CCEs and the Aβ monomer or Aβ fibrils showed only minimal effects. In addition, we provide evidence that induction of neuronal CCEs are autonomous to primary neurons cultured from the R1.40 mice. Finally, our results also demonstrate that Aβ oligomer treated neurons exhibit elevated levels of activated Akt and mTOR (mammalian T arget O f R apamycin) and that PI3K, Akt or mTOR inhibitors blocked Aβ oligomer-induced neuronal CCEs. Taken together, these results demonstrate that Aβ oligomer-based induction of neuronal CCEs involve the PI3K-Akt-mTOR pathway.
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?
In AD and DS-AD, increased Aβ accumulation activates the PI3K/Akt signaling pathway, contributing to hyperactivation of mTORC1.
“In AD and DS‐AD, increased Aβ accumulation activates the PI3K/Akt signaling pathway, contributing to hyperactivation of mTORC1. 11”
From Disruption of hippocampal upstream regulators of mTOR and insulin pathways in Down syndrome with Alzheimer's disease neuropathology: Preliminary observations (2026) · cites this paper as [11]
The Results section (page not specified) says Aβ oligomers activate PI3K–Akt–mTOR signaling, and the Discussion reports increased Akt and mTOR phosphorylation after oligomer exposure in cultured neurons. The paper also describes altered signaling in AD brains, but it does not establish this mechanism in DS-AD or specifically identify hyperactivation of mTORC1. Its experimental finding concerns Aβ oligomer exposure, not increased Aβ accumulation generally. (LLM, conf=0.87)
Experimental — accuracy not yet measured
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
1 retracted
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
Lesné, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., & Ashe, K. H. (2006) · Nature · doi:10.1038/nature04533 · Cited by 2,769 · cited 2× · see citing works
“0 μg/ml) range (similar to those used in the present study) including synaptic loss [15], inhibition of LTP [12] and impairment of memory in animal models of AD [19].”
BackgroundMethodRetractedShankar, G. M., Bloodgood, B. L., Townsend, M., Walsh, D. M., Selkoe, D. J., & Sabatini, B. L. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4970-06.2007 · Cited by 1,592 · see citing works
Regulation of NMDA receptor trafficking by amyloid-β
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., et al. (2005) · Nature Neuroscience · doi:10.1038/nn1503 · Cited by 1,561 · cited 1× · see citing works
“First, this pathway acts downstream of many cell surface receptors to which Aβ has been demonstrated to interact with including the alpha 7 nicotinic acetylcholine receptor (CHRNA7), N-methyl-D-aspartic acid receptors [35,36] and insulin receptors [20].”
Oligomeric and fibrillar species of amyloid-β peptides differentially affect neuronal viability
Dahlgren, K. N., Manelli, A. M., Stine, W. B., Baker, L. K., Krafft, G. A., & LaDu, M. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201750200 · Cited by 1,452 · see citing works
Lacor, P. N., Buniel, M. C., Furlow, P. W., Sanz Clemente, A., Velasco, P. T., Wood, M., Viola, K. L., & Klein, W. L. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3501-06.2007 · Cited by 1,188 · see citing works
Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model
Calon, F., Lim, G. P., Yang, F., Morihara, T., Teter, B., Ubeda, O., Rostaing, P., Triller, A., Salem, N., Ashe, K. H., et al. (2004) · Neuron · doi:10.1016/j.neuron.2004.08.013 · Cited by 707 · see citing works
Amyloid beta oligomers induce impairment of neuronal insulin receptors
Zhao, W., De Felice, F. G., Fernandez, S., Chen, H., Lambert, M. P., Quon, M. J., Krafft, G. A., & Klein, W. L. (2008) · The FASEB Journal · doi:10.1096/fj.06-7703com · Cited by 587 · see citing works
Cell-cycle reentry and cell death in transgenic mice expressing nonmutant human tau isoforms
Andorfer, C., Acker, C. M., Kress, Y., Hof, P. R., Duff, K., & Davies, P. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.4637-04.2005 · Cited by 511 · cited 1× · see citing works
“Third, neuronal CCEs are observed in a variety of transgenic mouse models of AD [3, 8 ].”
BackgroundGriffin, R. J., Moloney, A., Kelliher, M., Johnston, J. A., Ravid, R., Dockery, P., O'Connor, R., & O'Neill, C. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02949.x · Cited by 459 · see citing works
Li, X., Alafuzoff, I., Soininen, H., Winblad, B., & Pei, J. (2005) · The FEBS Journal · doi:10.1111/j.1742-4658.2005.04833.x · Cited by 324 · see citing works
TOR-Mediated Cell-Cycle Activation Causes Neurodegeneration in a Drosophila Tauopathy Model
Khurana, V., Lu, Y., Steinhilb, M. L., Oldham, S., Shulman, J. M., & Feany, M. B. (2006) · Current Biology · doi:10.1016/j.cub.2005.12.042 · Cited by 266 · see citing works
Flagged first, then by citations
Research works printed but not linked: 48
- Selkoe DJ Alzheimer's disease: genes, proteins, and therapy Physiol Rev 2001 81 741 766 11274343
- Cummings JL Cole G Alzheimer disease JAMA 2002 287 2335 2338 11988038 10.1001/jama.287.18.2335 · DOI
- Yang Y Mufson EJ Herrup K Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer's disease J Neurosci 2003 23 2557 2563 12684440 PMC6742098
- Husseman JW Nochlin D Vincent I Mitotic activation: a convergent mechanism for a cohort of neurodegenerative diseases Neurobiol Aging 2000 21 815 828 11124425 10.1016/S0197-4580(00)00221-9 · DOI
- Copani A Caraci F Hoozemans JJ Calafiore M Sortino MA Nicoletti F The nature of the cell cycle in neurons: focus on a "non-canonical" pathway of DNA replication causally related to death Biochim Biophys Acta 2007 1772 409 412 17196375
- Yang Y Herrup K Cell division in the CNS: protective response or lethal event in post-mitotic neurons? Biochim Biophys Acta 2007 1772 457 466 17158035 PMC2785903
- Rubin EH Morris JC Grant EA Vendegna T Very mild senile dementia of the Alzheimer type. I. Clinical assessment Arch Neurol 1989 46 379 382 2650663
- Varvel NH Bhaskar K Patil AR Pimplikar SW Herrup K Lamb BT Abeta oligomers induce neuronal cell cycle events in Alzheimer's disease J Neurosci 2008 28 10786 10793 18945886 10.1523/JNEUROSCI.2441-08.2008 PMC2680286 · DOI
- Yang Y Varvel NH Lamb BT Herrup K Ectopic cell cycle events link human Alzheimer's disease and amyloid precursor protein transgenic mouse models J Neurosci 2006 26 775 784 16421297 10.1523/JNEUROSCI.3707-05.2006 PMC6675370 · DOI
- Yan R Bienkowski MJ Shuck ME Miao H Tory MC Pauley AM Brashier JR Stratman NC Mathews WR Buhl AE Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity Nature 1999 402 533 537 10591213 10.1038/990107 · DOI · Paper page
- Wang HW Pasternak JF Kuo H Ristic H Lambert MP Chromy B Viola KL Klein WL Stine WB Krafft GA Trommer BL Soluble oligomers of beta amyloid (1–42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus Brain Res 2002 924 133 140 11750898 10.1016/S0006-8993(01)03058-X · DOI · Paper page
- Shankar GM Li S Mehta TH Garcia-Munoz A Shepardson NE Smith I Brett FM Farrell MA Rowan MJ Lemere CA Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory Nat Med 2008 14 837 842 18568035 10.1038/nm1782 PMC2772133 · DOI · Paper page
- Selkoe DJ Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and behavior Behav Brain Res 2008 192 106 113 18359102 10.1016/j.bbr.2008.02.016 PMC2601528 · DOI · Paper page
- Rowan MJ Klyubin I Wang Q Hu NW Anwyl R Synaptic memory mechanisms: Alzheimer's disease amyloid beta-peptide-induced dysfunction Biochem Soc Trans 2007 35 1219 1223 17956317 10.1042/BST0351219 · DOI
- Viola KL Velasco PT Klein WL Why Alzheimer's is a disease of memory: the attack on synapses by A beta oligomers (ADDLs) J Nutr Health Aging 2008 12 51S 57S 18165846 10.1007/BF02982587 · DOI
- Plum L Schubert M Bruning JC The role of insulin receptor signaling in the brain Trends Endocrinol Metab 2005 16 59 65 15734146 10.1016/j.tem.2005.01.008 · DOI · Paper page
- Lafay-Chebassier C Paccalin M Page G Barc-Pain S Perault-Pochat MC Gil R Pradier L Hugon J mTOR/p70S6k signalling alteration by Abeta exposure as well as in APP-PS1 transgenic models and in patients with Alzheimer's disease J Neurochem 2005 94 215 225 15953364 10.1111/j.1471-4159.2005.03187.x · DOI · Paper page
- Bitan G Lomakin A Teplow DB Amyloid beta-protein oligomerization: prenucleation interactions revealed by photo-induced cross-linking of unmodified proteins J Biol Chem 2001 276 35176 35184 11441003 10.1074/jbc.M102223200 · DOI
- Walsh DM Tseng BP Rydel RE Podlisny MB Selkoe DJ The oligomerization of amyloid beta-protein begins intracellularly in cells derived from human brain Biochemistry 2000 39 10831 10839 10978169 10.1021/bi001048s · DOI
- Walsh DM Townsend M Podlisny MB Shankar GM Fadeeva JV El Agnaf O Hartley DM Selkoe DJ Certain inhibitors of synthetic amyloid beta-peptide (Abeta) fibrillogenesis block oligomerization of natural Abeta and thereby rescue long-term potentiation J Neurosci 2005 25 2455 2462 15758153 10.1523/JNEUROSCI.4391-04.2005 PMC6725159 · DOI
- Wu Q Combs C Cannady SB Geldmacher DS Herrup K Beta-amyloid activated microglia induce cell cycling and cell death in cultured cortical neurons Neurobiol Aging 2000 21 797 806 11124423 10.1016/S0197-4580(00)00219-0 · DOI
- Malik B Currais A Soriano S Cell cycle-driven neuronal apoptosis specifically linked to amyloid peptide Abeta1–42 exposure is not exacerbated in a mouse model of presenilin-1 familial Alzheimer's disease J Neurochem 2008 106 912 916 18466334 10.1111/j.1471-4159.2008.05446.x · DOI
- McShea A Lee HG Petersen RB Casadesus G Vincent I Linford NJ Funk JO Shapiro RA Smith MA Neuronal cell cycle re-entry mediates Alzheimer disease-type changes Biochim Biophys Acta 2007 1772 467 472 17095196
- Calabrese B Shaked GM Tabarean IV Braga J Koo EH Halpain S Rapid, concurrent alterations in pre- and postsynaptic structure induced by naturally-secreted amyloid-beta protein Mol Cell Neurosci 2007 35 183 193 17368908 10.1016/j.mcn.2007.02.006 PMC2268524 · DOI
- Lambert MP Velasco PT Chang L Viola KL Fernandez S Lacor PN Khuon D Gong Y Bigio EH Shaw P Monoclonal antibodies that target pathological assemblies of Abeta J Neurochem 2007 100 23 35 17116235 10.1111/j.1471-4159.2006.04157.x · DOI · Paper page
- Wang HY Lee DH D'Andrea MR Peterson PA Shank RP Reitz AB beta-Amyloid(1–42) binds to alpha7 nicotinic acetylcholine receptor with high affinity. Implications for Alzheimer's disease pathology J Biol Chem 2000 275 5626 5632 10681545 10.1074/jbc.275.8.5626 · DOI
- Pei JJ Khatoon S An WL Nordlinder M Tanaka T Braak H Tsujio I Takeda M Alafuzoff I Winblad B Role of protein kinase B in Alzheimer's neurofibrillary pathology Acta Neuropathol 2003 105 381 392 12624792
- Shamji AF Nghiem P Schreiber SL Integration of growth factor and nutrient signaling: implications for cancer biology Mol Cell 2003 12 271 280 14536067 10.1016/j.molcel.2003.08.016 · DOI
- Wei W Wang X Kusiak JW Signaling events in amyloid beta-peptide-induced neuronal death and insulin-like growth factor I protection J Biol Chem 2002 277 17649 17656 11882652 10.1074/jbc.M111704200 · DOI
- Frasca G Chiechio S Vancheri C Nicoletti F Copani A Angela Sortino M Beta-amyloid-activated cell cycle in SH-SY5Y neuroblastoma cells: correlation with the MAP kinase pathway J Mol Neurosci 2004 22 231 236 14997017 10.1385/JMN:22:3:231 · DOI
- Small DH Fodero LR Cholinergic regulation of synaptic plasticity as a therapeutic target in Alzheimer's disease J Alzheimers Dis 2002 4 349 355 12446967
- Fisher A Pittel Z Haring R Bar-Ner N Kliger-Spatz M Natan N Egozi I Sonego H Marcovitch I Brandeis R M1 muscarinic agonists can modulate some of the hallmarks in Alzheimer's disease: implications in future therapy J Mol Neurosci 2003 20 349 356 14501019 10.1385/JMN:20:3:349 · DOI
- Parameshwaran K Dhanasekaran M Suppiramaniam V Amyloid beta peptides and glutamatergic synaptic dysregulation Exp Neurol 2008 210 7 13 18053990 10.1016/j.expneurol.2007.10.008 · DOI
- Ott MO Bullock SL A gene trap insertion reveals that amyloid precursor protein expression is a very early event in murine embryogenesis Dev Genes Evol 2001 211 355 357 11466532 10.1007/s004270100158 · DOI
- Fisher S Gearhart JD Oster-Granite ML Expression of the amyloid precursor protein gene in mouse oocytes and embryos Proc Natl Acad Sci USA 1991 88 1779 1782 1900367 10.1073/pnas.88.5.1779 PMC51108 · DOI
- De Strooper B Annaert W Proteolytic processing and cell biological functions of the amyloid precursor protein J Cell Sci 2000 113 1857 1870 10806097
- Damjanac M Rioux Bilan A Paccalin M Pontcharraud R Fauconneau B Hugon J Page G Dissociation of Akt/PKB and ribosomal S6 kinase signaling markers in a transgenic mouse model of Alzheimer's disease Neurobiol Dis 2008 29 354 367 18023354 10.1016/j.nbd.2007.09.008 · DOI · Paper page
- Peltier J O'Neill A Schaffer DV PI3K/Akt and CREB regulate adult neural hippocampal progenitor proliferation and differentiation Dev Neurobiol 2007 67 1348 1361 17638387 10.1002/dneu.20506 · DOI · Paper page
- Garza JC Guo M Zhang W Lu XY Leptin increases adult hippocampal neurogenesis in vivo and in vitro J Biol Chem 2008 283 18238 18247 18367451 10.1074/jbc.M800053200 PMC2440628 · DOI
- Zemke D Azhar S Majid A The mTOR pathway as a potential target for the development of therapies against neurological disease Drug News Perspect 2007 20 495 499 18080036 10.1358/dnp.2007.20.8.1157618 · DOI
- Walsh DM Lomakin A Benedek GB Condron MM Teplow DB Amyloid beta-protein fibrillogenesis. Detection of a protofibrillar intermediate J Biol Chem 1997 272 22364 22372 9268388 10.1074/jbc.272.35.22364 · DOI
- Hou L Zagorski MG Sorting out the driving forces for parallel and antiparallel alignment in the abeta peptide fibril structure Biophys J 2004 86 1 2 14695243 10.1016/S0006-3495(04)74077-1 PMC1303772 · DOI
- Ingle JDJ Crouch SR Spectrochemical Analysis 1988 New Jersey: Prentice Hall
- Cicero S Herrup K Cyclin-dependent kinase 5 is essential for neuronal cell cycle arrest and differentiation J Neurosci 2005 25 9658 9668 16237170 10.1523/JNEUROSCI.1773-05.2005 PMC6725732 · DOI
- Powis G Bonjouklian R Berggren MM Gallegos A Abraham R Ashendel C Zalkow L Matter WF Dodge J Grindey G Wortmannin, a potent and selective inhibitor of phosphatidylinositol-3-kinase Cancer Res 1994 54 2419 2423 8162590
- Barnett SF Bilodeau MT Lindsley CW The Akt/PKB family of protein kinases: a review of small molecule inhibitors and progress towards target validation Curr Top Med Chem 2005 5 109 125 15853641 10.2174/1568026053507714 · DOI
- Mita MM Mita A Rowinsky EK The molecular target of rapamycin (mTOR) as a therapeutic target against cancer Cancer Biol Ther 2003 2 S169 177 14508096
- Sarkar M Kuret J Lee G Two motifs within the tau microtubule-binding domain mediate its association with the hsc70 molecular chaperone J Neurosci Res 2008 18500754 PMC4271846
Cited by
Sorted by citations
Talbot, K., Wang, H.-Y., Kazi, H., Han, L.-Y., Bakshi, K. P., Stucky, A., Fuino, R. L., Kawaguchi, K. R., Samoyedny, A. J., Wilson, R. S., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59903 · Cited by 1,871 · see citing works
Molecular Interplay between Mammalian Target of Rapamycin (mTOR), Amyloid-β, and Tau
Caccamo, A., Majumder, S., Richardson, A., Strong, R., & Oddo, S. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.100420 · Cited by 881 · see citing works
The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade
Cline, E. N., Bicca, M. A., Viola, K. L., & Klein, W. L. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179941 · Cited by 870 · see citing works
Regulation of Tau Pathology by the Microglial Fractalkine Receptor
Bhaskar, K., Konerth, M., Kokiko-Cochran, O. N., Cardona, A., Ransohoff, R. M., & Lamb, B. T. (2010) · Neuron · doi:10.1016/j.neuron.2010.08.023 · Cited by 639 · see citing works
Self-citationBordi, M., Berg, M. J., Mohan, P. S., Peterhoff, C. M., Alldred, M. J., Che, S., Ginsberg, S. D., & Nixon, R. A. (2016) · Autophagy · doi:10.1080/15548627.2016.1239003 · Cited by 353 · see citing works
Tramutola, A., Triplett, J. C., Di Domenico, F., Niedowicz, D. M., Murphy, M. P., Coccia, R., Perluigi, M., & Butterfield, D. A. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13037 · Cited by 347 · see citing works
Mammalian/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration
Querfurth, H., & Lee, H.-K. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00428-5 · Cited by 288 · see citing works
Selective suppression of the α isoform of p38 MAPK rescues late-stage tau pathology
Maphis, N., Jiang, S., Xu, G., Kokiko-Cochran, O. N., Roy, S. M., Van Eldik, L. J., Watterson, D. M., Lamb, B. T., & Bhaskar, K. (2016) · Alzheimer's Research & Therapy · doi:10.1186/s13195-016-0221-y · Cited by 144 · see citing works
Self-citationLoss of tau rescues inflammation-mediated neurodegeneration
Maphis, N., Xu, G., Kokiko-Cochran, O. N., Cardona, A. E., Ransohoff, R. M., Lamb, B. T., & Bhaskar, K. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00196 · Cited by 91 · see citing works
Self-citationDi Domenico, F., Tramutola, A., Foppoli, C., Head, E., Perluigi, M., & Butterfield, D. A. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.08.009 · Cited by 89 · see citing works
Targeting mTOR to reduce Alzheimer-related cognitive decline: from current hits to future therapies.
Tramutola, A., Lanzillotta, C., & Di Domenico, F. (2017) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2017.1244482 · Cited by 69 · see citing works
Ali, T., Rehman, S. U., Khan, A., Badshah, H., Abid, N. B., Kim, M. W., Jo, M. H., Chung, S. S., Lee, H.-G., Rutten, B. P. F., et al. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00445-4 · Cited by 65 · see citing works
Lee, H.-K., Kwon, B., Lemere, C. A., de la Monte, S., Itamura, K., Ha, A. Y., & Querfurth, H. W. (2017) · Journal of Alzheimer's Disease · doi:10.3233/jad-161029 · Cited by 57 · see citing works
Bidirectional modulation of Alzheimer phenotype by alpha-synuclein in mice and primary neurons
Khan, S. S., LaCroix, M., Boyle, G., Sherman, M. A., Brown, J. L., Amar, F., Aldaco, J., Lee, M. K., Bloom, G. S., & Lesné, S. E. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1886-z · Cited by 41 · see citing works
Querfurth, H., Marshall, J., Parang, K., Rioult-Pedotti, M. S., Tiwari, R., Kwon, B., Reisinger, S., & Lee, H.-K. (2022) · PLOS ONE · doi:10.1371/journal.pone.0261696 · Cited by 9 · see citing works
The mTOR pathway: a common link between Alzheimer's disease and Down Syndrome
Wohlfert, A. J., Phares, J., & Granholm, A.-C. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13206183 · Cited by 6 · see citing works
Adriaanse, B. A., Brady, S., Wang, M., Beard, D. J., Spencer, J. I., Pansieri, J., Sutherland, B. A., Esiri, M. M., Buchan, A. M., Cader, Z., et al. (2023) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12904 · Cited by 2 · see citing works
“Others have previously shown amyloid increases mTOR activation and that mTOR activation increases amyloid build-up [14, 44], so these findings are unexpected.”
BackgroundNordbeck, A. J., Martá‐Ariza, M., Ek Olofsson, H., Kanshin, E., Ueberheide, B., Jones, K., Sanford, B., Hamlett, E. D., Head, E., Mufson, E. J., et al. (2026) · Alzheimer's & Dementia · doi:10.1002/alz.71776
“11 While the implications of aberrant mTORC2 signaling are poorly understood, the hyperactivation of mTORC1 is linked to dysregulationofautophagy,proteinsynthesis,andclearanceofcellular debris.”
- Authors
- Bhaskar, K., Miller, M., Chludzinski, A., Herrup, K., Zagorski, M., & Lamb, B. T.
- Affiliations
- Cleveland Clinic (US)
- Case Western Reserve University (US)
- Cleveland Clinic Lerner College of Medicine (US)
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Lamb, Bruce T
- Venue
- Molecular Neurodegeneration
- Published
- 2009-03-16
- Volume
- 4
- Issue
- 1
- Pages
- 14-14
- ISSN
- 1750-1326 (ISSN-L)
- PMC
- PMC2663563
- OpenAlex
- W1989723191
- Cited by
- 177
- References
- 11
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 7 · 2023: 8 · 2022: 5 · 2021: 18 · 2020: 14 · 2019: 12 · 2018: 6 · 2017: 10 · 2016: 12 · 2015: 14 · 2014: 13 · 2013: 11 · 2012: 11
- FWCI
- 7.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Molecular Neurodegeneration (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- Alzheimer's Association
- Northwestern University
- National Institutes of Health (AG023012)
- National Institute on Aging (R01AG023012, R01AG027853, R01AG024494)
- National Institute of Neurological Disorders and Stroke (R01NS020591)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- PI3K/AKT/mTOR pathway, amyloid-beta oligomers, neuronal cell cycle re-entry, Alzheimer's disease, amyloid precursor protein, cortical neurons, Akt activation, mTOR activation, PI3K inhibitors, APP processing
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
