Deciphering the mechanism underlying late-onset Alzheimer disease
Open accessAbstract
Drug development efforts for late-onset Alzheimer disease (AD) have met with disappointing results. Krstic and Knuesel argue for a re-evaluation of pathological mechanisms underlying the disease, with a shift of focus away from amyloid-β as the key therapeutic target. Through integration of their own research with the wider literature, they present a model that places inflammation and impairments in axonal functions and integrity at the heart of AD pathology. Despite tremendous investments in understanding the complex molecular mechanisms underlying Alzheimer disease (AD), recent clinical trials have failed to show efficacy. A potential problem underlying these failures is the assumption that the molecular mechanism mediating the genetically determined form of the disease is identical to the one resulting in late-onset AD. Here, we integrate experimental evidence outside the 'spotlight' of the genetic drivers of amyloid-β (Aβ) generation published during the past two decades, and present a mechanistic explanation for the pathophysiological changes that characterize late-onset AD. We propose that chronic inflammatory conditions cause dysregulation of mechanisms to clear misfolded or damaged neuronal proteins that accumulate with age, and concomitantly lead to tau-associated impairments of axonal integrity and transport. Such changes have several neuropathological consequences: focal accumulation of mitochondria, resulting in metabolic impairments; induction of axonal swelling and leakage, followed by destabilization of synaptic contacts; deposition of amyloid precursor protein in swollen neurites, and generation of aggregation-prone peptides; further tau hyperphosphorylation, ultimately resulting in neurofibrillary tangle formation and neuronal death. The proposed sequence of events provides a link between Aβ and tau-related neuropathology, and underscores the concept that degenerating neurites represent a cause rather than a consequence of Aβ accumulation in late-onset AD.
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?
Growing evidence supports chronic inflammation as a major cause or contributor to Alzheimer's pathology.
“Growing evidence supports chronic inflammation as a major cause or contributor to Alzheimer's pathology.16”
From Whole-genome sequencing suggests a chemokine gene cluster that modifies age at onset in familial Alzheimer's disease (2015) · cites this paper as [16]
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
Part of this paper’s reference list could not be split into single entries.
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429 · see citing works
Alzheimer's disease: the amyloid cascade hypothesis
Hardy, J. A., & Higgins, G. A. (1992) · Science · doi:10.1126/science.1566067 · Cited by 7,484 · see citing works
Global prevalence of dementia: a Delphi consensus study
Ferri, C. P., Prince, M. J., Brayne, C., Brodaty, H., Fratiglioni, L., Ganguli, M., Hall, K. S., Hasegawa, K., Hendrie, H. C., Huang, Y., et al. (2005) · The Lancet · doi:10.1016/s0140-6736(05)67889-0 · Cited by 5,336 · see citing works
A Meta-Analysis of Cytokines in Major Depression
Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., & Lanctôt, K. L. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.09.033 · Cited by 4,729 · see citing works
Neuropathological alterations in Alzheimer disease
Serrano-Pozo, A., Frosch, M. P., Masliah, E., & Hyman, B. T. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006189 · Cited by 3,345 · see citing works
Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.440 · Cited by 3,326 · see citing works
Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders
Zlokovic, B. V. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3114 · Cited by 2,969 · see citing works
Molecular mechanisms of mTOR-mediated translational control
Ma, X. M., & Blenis, J. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2672 · Cited by 2,558 · see citing works
Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease
the European Alzheimer's Disease Initiative Investigators, Lambert, J.-C., Heath, S., Even, G., Campion, D., Sleegers, K., Hiltunen, M., Combarros, O., Zelenika, D., Bullido, M. J., et al. (2009) · Nature Genetics · doi:10.1038/ng.439 · Cited by 2,234 · see citing works
Stages of the Pathologic Process in Alzheimer Disease: Age Categories From 1 to 100 Years
Braak, H., Thal, D. R., Ghebremedhin, E., & Del Tredici, K. (2011) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e318232a379 · Cited by 2,194 · see citing works
Franceschi, C., Capri, M., Monti, D., Giunta, S., Olivieri, F., Sevini, F., Panourgia, M. P., Invidia, L., Celani, L., Scurti, M., et al. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.016 · Cited by 2,087 · see citing works
Gene regulation and DNA damage in the ageing human brain
Lu, T., Pan, Y., Kao, S.-Y., Li, C., Kohane, I., Chan, J., & Yankner, B. A. (2004) · Nature · doi:10.1038/nature02661 · Cited by 1,874 · see citing works
Extensive Involvement of Autophagy in Alzheimer Disease: An Immuno-Electron Microscopy Study
Nixon, R. A., Wegiel, J., Kumar, A., Yu, W. H., Peterhoff, C., Cataldo, A., & Cuervo, A. M. (2005) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/64.2.113 · Cited by 1,588 · see citing works
Ownby, R. L., Crocco, E., Acevedo, A., John, V., & Loewenstein, D. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.5.530 · Cited by 1,493 · see citing works
McGeer, P. L., Schulzer, M., & McGeer, E. G. (1996) · Neurology · doi:10.1212/wnl.47.2.425 · Cited by 1,367 · see citing works
Amyloid-β and tau — a toxic pas de deux in Alzheimer's disease
Ittner, L. M., & Götz, J. (2010) · Nature reviews. Neuroscience · doi:10.1038/nrn2967 · Cited by 1,357 · see citing works
Wyss-Coray (2006) · doi:10.1038/nm1484 · Cited by 1,284 · see citing works
Axonopathy and Transport Deficits Early in the Pathogenesis of Alzheimer’s Disease
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., et al. (2005) · Science · doi:10.1126/science.1105681 · Cited by 1,214 · see citing works
Systemic inflammation and disease progression in Alzheimer disease
Holmes, C., Cunningham, C., Zotova, E., Woolford, J., Dean, C., Kerr, S., Culliford, D., & Perry, V. H. (2009) · Neurology · doi:10.1212/wnl.0b013e3181b6bb95 · Cited by 1,139 · see citing works
Wada, K., Tanaka, K., & Nakashima, K. (2011) · PubMed · Cited by 1,132 · see citing works
Hoover, B. R., Reed, M. N., Su, J., Penrod, R. D., Kotilinek, L. A., Grant, M. K., Pitstick, R., Carlson, G. A., Lanier, L. M., Yuan, L.-L., et al. (2010) · Neuron · doi:10.1016/j.neuron.2010.11.030 · Cited by 1,118 · see citing works
A Meta-Analysis of Cytokines in Alzheimer's Disease
Swardfager, W., Lanctôt, K., Rothenburg, L., Wong, A., Cappell, J., & Herrmann, N. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.06.012 · Cited by 1,108 · see citing works
Gene-expression profile of the ageing brain in mice
Lee, C.-K., Weindruch, R., & Prolla, T. A. (2000) · Nature Genetics · doi:10.1038/77046 · Cited by 1,055 · see citing works
Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment
Scheff, S. W., Price, D. A., Schmitt, F. A., & Mufson, E. J. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.09.012 · Cited by 1,017 · see citing works
Macroautophagy—a novel β-amyloid peptide-generating pathway activated in Alzheimer's disease
Yu, W. H., Cuervo, A. M., Kumar, A., Peterhoff, C. M., Schmidt, S. D., Lee, J.-H., Mohan, P. S., Mercken, M., Farmery, M. R., Tjernberg, L. O., et al. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200505082 · Cited by 967 · see citing works
Jin, M., Shepardson, N., Yang, T., Chen, G., Walsh, D., & Selkoe, D. J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1017033108 · Cited by 876 · see citing works
Godbout, J. P., Chen, J., Abraham, J., Richwine, A. F., Berg, B. M., Kelley, K. W., & Johnson, R. W. (2005) · The FASEB Journal · doi:10.1096/fj.05-3776fje · Cited by 813 · see citing works
Review: microglia of the aged brain: primed to be activated and resistant to regulation
Norden, D. M., & Godbout, J. P. (2013) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2012.01306.x · Cited by 792 · see citing works
Meyer, U., Nyffeler, M., Engler, A., Urwyler, A., Schedlowski, M., Knuesel, I., Yee, B. K., & Feldon, J. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0099-06.2006 · Cited by 774 · see citing works
Self-citationPrecursor 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
Streit, W. J., Braak, H., Xue, Q.-S., & Bechmann, I. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0556-6 · Cited by 727 · see citing works
DEFECTIVE BRAIN MICROTUBULE ASSEMBLY IN ALZHEIMER'S DISEASE
Iqbal, K., Zaidi, T., Wen, G. Y., Grundke, I., MERZ, P. A., Shaikh, S., Wisniewski, H., Alafuzoff, I. I., & Winblad, B. G. (1986) · The Lancet · doi:10.1016/s0140-6736(86)92134-3 · Cited by 727 · see citing works
Early inflammation and dementia: A 25‐year follow‐up of the Honolulu‐Asia aging study
Schmidt, R., Schmidt, H., Curb, J. D., Masaki, K., White, L. R., & Launer, L. J. (2002) · Annals of Neurology · doi:10.1002/ana.10265 · Cited by 710 · see citing works
The role of microglia in amyloid clearance from the AD brain
Lee, C. Y. D., & Landreth, G. E. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0433-4 · Cited by 701 · 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
Autophagy Failure in Alzheimer's Disease – Locating the Primary Defect
Nixon, R., & Yang, D.-S. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.01.021 · Cited by 634 · see citing works
Tau phosphorylation in neuronal cell function and dysfunction
Johnson, G. V. W., & Stoothoff, W. H. (2004) · Journal of Cell Science · doi:10.1242/jcs.01558 · Cited by 624 · see citing works
Widespread tau and amyloid-beta pathology many years after a single traumatic brain injury in humans
Johnson, V. E., Stewart, W., & Smith, D. H. (2012) · Brain Pathology · doi:10.1111/j.1750-3639.2011.00513.x · Cited by 620 · see citing works
Peri, F., & Nüsslein-Volhard, C. (2008) · Cell · doi:10.1016/j.cell.2008.04.037 · Cited by 617 · see citing works
Crystal, H., Dickson, D., Fuld, P., Masur, D., Scott, R., Mehler, M., Masdeu, J., Kawas, C., Aronson, M., & Wolfson, L. (1988) · Neurology · doi:10.1212/wnl.38.11.1682 · Cited by 586 · see citing works
Henry, C. J., Huang, Y., Wynne, A. M., & Godbout, J. P. (2009) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2008.09.002 · Cited by 565 · see citing works
Li, Y., Liu, L., Barger, S. W., & Griffin, W. S. T. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-05-01605.2003 · Cited by 563 · see citing works
Castellani, R. J., Rolston, R. K., & Smith, M. A. (2010) · Disease-a-Month · doi:10.1016/j.disamonth.2010.06.001 · Cited by 561 · see citing works
Casserly, I., & Topol, E. J. (2004) · The Lancet · doi:10.1016/s0140-6736(04)15900-x · Cited by 560 · see citing works
Immunoproteasomes Preserve Protein Homeostasis upon Interferon-Induced Oxidative Stress
Seifert, U., Biały, Ł. P., Ebstein, F., Bech‐Otschir, D., Beling, A., Schröter, F., Prozorovski, T., Lange, N., Steffen, J., Rieger, M., et al. (2010) · Cell · doi:10.1016/j.cell.2010.07.036 · Cited by 554 · see citing works
Hutchinson, E. (2011) · Nature reviews. Neuroscience · doi:10.1038/nrn2985 · Cited by 534 · see citing works
Caspase activation precedes and leads to tangles
de Calignon, A., Fox, L. M., Pitstick, R., Carlson, G. A., Bacskai, B. J., Spires-Jones, T. L., & Hyman, B. T. (2010) · Nature · doi:10.1038/nature08890 · Cited by 517 · see citing works
Edison, P., Archer, H. A., Gerhard, A., Hinz, R., Pavese, N., Turkheimer, F. E., Hammers, A., Tai, Y. F., Fox, N., Kennedy, A., et al. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.08.001 · Cited by 513 · see citing works
Cribbs, D. H., Berchtold, N. C., Perreau, V., Coleman, P. D., Rogers, J., Tenner, A. J., & Cotman, C. W. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-179 · Cited by 499 · see citing works
Lee, S., Satō, Y., & Nixon, R. A. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.6412-10.2011 · Cited by 471 · see citing works
Abnormal bundling and accumulation of F-actin mediates tau-induced neuronal degeneration in vivo
Fulga, T. A., Elson-Schwab, I., Khurana, V., Steinhilb, M. L., Spires, T. L., Hyman, B. T., & Feany, M. B. (2007) · Nature Cell Biology · doi:10.1038/ncb1528 · Cited by 452 · see citing works
Enzymatically active lysosomal proteases are associated with amyloid deposits in Alzheimer brain.
Cataldo, A., & Nixon, R. (1990) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.87.10.3861 · Cited by 436 · see citing works
Brecht, W. J., Harris, F. M., Chang, S., Tesseur, I., Yu, G.-Q., Xu, Q., Dee Fish, J., Wyss-Coray, T., Buttini, M., Mucke, L., et al. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.4315-03.2004 · Cited by 403 · see citing works
A Randomized, Double-Blind, Study of Rofecoxib in Patients with Mild Cognitive Impairment
on behalf of the Rofecoxib Protocol 078 study group, Thal, L. J., Ferris, S. H., Kirby, L., Block, G. A., Lines, C. R., Yuen, E., Assaid, C., Nessly, M. L., Norman, B. A., et al. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300690 · Cited by 402 · see citing works
Formation and maintenance of Alzheimer's disease β-amyloid plaques in the absence of microglia
Grathwohl, S. A., Kälin, R. E., Bolmont, T., Prokop, S., Winkelmann, G., Kaeser, S. A., Odenthal, J., Radde, R., Eldh, T., Gandy, S., et al. (2009) · Nature Neuroscience · doi:10.1038/nn.2432 · Cited by 401 · see citing works
Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice
Krstic, D., Madhusudan, A., Doehner, J., Vogel, P., Notter, T., Imhof, C., Manalastas, A., Hilfiker, M., Pfister, S., Schwerdel, C., et al. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-151 · Cited by 400 · see citing works
Sheng, J. (2003) · Neurobiology of Disease · doi:10.1016/s0969-9961(03)00069-x · Cited by 388 · see citing works
Reimagining Alzheimer's Disease—An Age-Based Hypothesis
Herrup, K. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.4521-10.2010 · Cited by 386 · see citing works
Aging and Alzheimer's Disease: Lessons From the Nun Study
Snowdon, D. A. (1997) · The Gerontologist · doi:10.1093/geront/37.2.150 · Cited by 367 · see citing works
Njie, E. G., Boelen, E., Stassen, F. R., Steinbusch, H. W. M., Borchelt, D. R., & Streit, W. J. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.05.008 · Cited by 335 · see citing works
Peripheral infection and aging interact to impair hippocampal memory consolidation
Barrientos, R. M., Higgins, E. A., Biedenkapp, J. C., Sprunger, D. B., Wright-Hardesty, K. J., Watkins, L. R., Rudy, J. W., & Maier, S. F. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.03.010 · Cited by 330 · see citing works
Extended results of the Alzheimer's disease anti‐inflammatory prevention trial
Breitner, J. C. S., Baker, L. D., Montine, T. J., Meinert, C. L., Lyketsos, C. G., Ashe, K. H., Brandt, J., Craft, S., Evans, D. A., Green, R. C., et al. (2011) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2010.12.014 · Cited by 327 · see citing works
Cunningham, C., Campion, S., Teeling, J., Felton, L., & Perry, V. H. (2007) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2006.12.007 · Cited by 318 · see citing works
Cytochrome c Release and Caspase Activation in Traumatic Axonal Injury
Büki, A., Okonkwo, D. O., Wang, K., & Povlishock, J. T. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-08-02825.2000 · Cited by 301 · see citing works
Lue, L. F., Brachova, L., CIVIN, W. H., & Rogers, J. (1996) · PubMed · Cited by 299 · see citing works
Mouzon, B., Chaytow, H., Crynen, G. C., Bachmeier, C. J., Stewart, J., MULLAN, M. J., Stewart, W. B., Jr., & Crawford, F. (2012) · Journal of Neurotrauma · doi:10.1089/neu.2012.2498 · Cited by 294 · see citing works
Axonal Transport and Alzheimer's Disease
Stokin, G. B., & Goldstein, L. S. B. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.103004.142637 · Cited by 292 · see citing works
The Pathogenesis of Alzheimer Disease: An Alternative to the Amyloid Hypothesis
Terry, R. D. (1996) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199655100-00001 · Cited by 291 · see citing works
Biessels, G. J., & Kappelle, L. J. (2005) · Biochemical Society Transactions · doi:10.1042/bst0331041 · Cited by 288 · see citing works
Kanaan, N. M., Morfini, G. A., LaPointe, N. E., Pigino, G. F., Patterson, K. R., Song, Y., Andreadis, A., Fu, Y., Brady, S. T., & Binder, L. I. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0560-11.2011 · Cited by 273 · see citing works
Kamer, A. R., Craig, R. G., Pirraglia, E., Dasanayake, A. P., Norman, R. G., Boylan, R. J., Nehorayoff, A., Glodzik, L., Bryś, M., & de Leon, M. J. (2009) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2009.08.013 · Cited by 271 · see citing works
Sheng, J. G., Ito, K., Skinner, R. D., Mrak, R. E., Rovnaghi, C. R., van Eldik, L. J., & Griffin, W. S. T. (1996) · Neurobiology of Aging · doi:10.1016/0197-4580(96)00104-2 · Cited by 269 · see citing works
Formation and maintenance of Alzheimer’s disease beta-amyloid plaques in the absence of microglia
Grathwohl, S. A., Kälin, R., Bolmont, T., Prokop, S., Winkelmann, G., Kaeser, S. A., Odenthal, J., Radde, R., Eldh, T., Gandy, S. E., et al. (2010) · e-Neuroforum · doi:10.1515/nf-2010-0107 · Cited by 269 · see citing works
Forloni, G., Demicheli, F., Giorgi, S., Bendotti, C., & Angeretti, N. (1992) · Molecular Brain Research · doi:10.1016/0169-328x(92)90202-m · Cited by 255 · see citing works
Lue, L.-F., Brachova, L., Civin, H. W., & Rogers, J. (1996) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199655100-00008 · Cited by 246 · see citing works
Caspase-9 Activation and Caspase Cleavage of tau in the Alzheimer's Disease Brain
Rohn, T. T., Rissman, R. A., Davis, M. C., Kim, Y., Cotman, C. W., & Head, E. (2002) · Neurobiology of Disease · doi:10.1006/nbdi.2002.0549 · Cited by 242 · see citing works
Barrientos, R. M., Frank, M. G., Hein, A. M., Higgins, E. A., Watkins, L. R., Rudy, J. W., & Maier, S. F. (2009) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2008.07.002 · Cited by 226 · see citing works
Microglia activation in sepsis: a case-control study.
Lemstra, A. W., Woud, J. C. G. I., Hoozemans, J. J. M., van Haastert, E. S., Rozemüller, A. J. M., Eikelenboom, P., & van Gool, W. A. (2007) · Journal of Neuroinflammation · doi:10.1186/1742-2094-4-4 · Cited by 224 · see citing works
Meyer, U., Nyffeler, M., Schwendener, S., Knuesel, I., Yee, B. K., & Feldon, J. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301413 · Cited by 215 · see citing works
Self-citationHannestad, J. O., Gallezot, J., Schafbauer, T., Lim, K., Kloczynski, T., Morris, E. D., Carson, R. E., Ding, Y., & Cosgrove, K. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2012.06.055 · Cited by 213 · see citing works
Sergeant, N., Bombois, S., Ghestem, A., Drobecq, H., Kostanjevečki, V., Missiaen, C., Wattez, A., David, J. P., Vanmechelen, E., Sergheraert, C., et al. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01818.x · Cited by 213 · see citing works
Chung, H., Brazil, M. I., Soe, T. T., & Maxfield, F. R. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.45.32301 · Cited by 212 · see citing works
Shahpasand, K., Uemura, I., Saito, T., Asano, T., Hata, K., Shibata, K., Toyoshima, Y., Hasegawa, M., & Hisanaga, S.-I. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.5927-11.2012 · Cited by 206 · see citing works
Inflammatory changes parallel the early stages of Alzheimer disease
Parachikova, A., Agadjanyan, M. G., Cribbs, D. H., Blurton-Jones, M., Perreau, V., Rogers, J., Beach, T. G., & Cotman, C. W. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.08.014 · Cited by 203 · see citing works
Association between Dementia and Infectious Disease
Dunn, N. R., Mullee, M., Perry, V. H., & Holmes, C. (2005) · Alzheimer Disease & Associated Disorders · doi:10.1097/01.wad.0000165511.52746.1f · Cited by 198 · see citing works
Mitofusin2 Mutations Disrupt Axonal Mitochondrial Positioning and Promote Axon Degeneration
Misko, A. L., Sasaki, Y., Tuck, E. J., Milbrandt, J., & Baloh, R. H. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.6338-11.2012 · Cited by 195 · see citing works
Sheng, J. G., Mrak, R. E., & Griffin, W. S. T. (1997) · Acta Neuropathologica · doi:10.1007/s004010050664 · Cited by 191 · see citing works
APP and APLP2 are essential at PNS and CNS synapses for transmission, spatial learning and LTP
Weyer, S. W., Klevanski, M., Delekate, A., Võikar, V., Aydin, D., Hick, M., Filippov, M. A., Drost, N., Schaller, K., Saar, M., et al. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.119 · Cited by 187 · see citing works
Local neuroinflammation and the progression of Alzheimer’s disease
McGeer, P., & Mcgeer, E. (2011) · Journal of Neurovirology · doi:10.1080/13550280290100969 · Cited by 181 · see citing works
Cunningham, C. M., & MacLullich, A. M. J. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.07.012 · Cited by 178 · 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
Yokokura, M., Mori, N., Yagi, S., Yoshikawa, E., Kikuchi, M., Yoshihara, Y., Wakuda, T., Sugihara, G., Takebayashi, K., Suda, S., et al. (2011) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-010-1612-0 · Cited by 174 · see citing works
Griffin, W. S. T., Sheng, J. G., Gentleman, S. M., Graham, D. I., Mrak, R. E., & Roberts, G. W. (1994) · Neuroscience Letters · doi:10.1016/0304-3940(94)90066-3 · Cited by 170 · see citing works
(1994) · PubMed Central · Cited by 169 · see citing works
Long-term impact of systemic bacterial infection on the cerebral vasculature and microglia
Püntener, U., Booth, S. G., Perry, V. H., & Teeling, J. L. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-146 · Cited by 163 · see citing works
Accumulation of tau induced in neurites by microglial proinflammatory mediators
Gorlovoy, P., Larionov, S., Pham, T. T. H., & Neumann, H. (2009) · The FASEB Journal · doi:10.1096/fj.08-123877 · Cited by 156 · see citing works
Stieber, A., Mourelatos, Z. P., & Gonatas, N. K. (1996) · PubMed · Cited by 142 · see citing works
Iijima-Ando, K., Sekiya, M., Maruko-Otake, A., Ohtake, Y., Suzuki, E., Lu, B., & Iijima, K. M. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002918 · Cited by 142 · see citing works
Tesseur, I. C., Dorpe, J. V., Bruynseels, K., Bronfman, F. C., Sciot, R., Lommel, A. V., & LEUVEN, F. V. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64788-8 · Cited by 141 · see citing works
Castellani, R. J., Lee, H., Siedlak, S. L., Nunomura, A., Hayashi, T., Nakamura, M., Zhu, X., Perry, G. L., & Smith, M. A. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1151 · Cited by 140 · see citing works
The amyloid cascade hypothesis
Korczyn, A. D. (2008) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2007.11.008 · Cited by 136 · see citing works
Early axonopathy preceding neurofibrillary tangles in mutant tau transgenic mice
Leroy, K., Bretteville, A., Schindowski, K., Gilissen, E., Authelet, M., De Decker, R., Yilmaz, Z., Buée, L., & Brion, J.-P. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.070345 · Cited by 135 · see citing works
Lazarov, O., Morfini, G. A., Pigino, G. F., Gadadhar, A., Chen, X., Robinson, J., Ho, H., Brady, S. T., & Sisodia, S. S. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.4272-06.2007 · Cited by 135 · see citing works
Kocherhans, S., Madhusudan, A., Doehner, J., Breu, K. S., Nitsch, R. M., Fritschy, J.-M., & Knuesel, I. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0418-10.2010 · Cited by 132 · see citing works
Self-citationAxonopathy in an APP/PS1 transgenic mouse model of Alzheimer’s disease
Wirths, O., Weis, J., Szczygielski, J., Multhaup, G., & Bayer, T. A. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0041-4 · Cited by 130 · see citing works
Sickness behavior, its mechanisms and significance
Tizard, I. R. (2008) · Animal Health Research Reviews · doi:10.1017/s1466252308001448 · Cited by 129 · see citing works
Schaaf, M. J. M., Hoetelmans, R. W. M., de Kloet, E. R., & Vreugdenhil, E. (1997) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19970515)48:4 · Cited by 127 · see citing works
Transgenic mice overexpressing amyloid beta protein are an incomplete model of Alzheimer disease
Schwab, C., Hosokawa, M., & McGeer, P. L. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2004.03.016 · Cited by 121 · see citing works
Depression and the Risk of Alzheimer Disease
Andersen, K., Lolk, A., rensen, P. K.-S., Petersen, N. E., & Green, A. (2005) · Epidemiology · doi:10.1097/01.ede.0000152116.32580.24 · Cited by 113 · see citing works
Amyloid Precursor Protein Is Trafficked and Secreted via Synaptic Vesicles
Groemer, T. W., Thiel, C. S., Holt, M. G., Riedel, D., Hua, Y., Hüve, J., Wilhelm, B. G., & Klingauf, J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018754 · 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
Morimoto, K., Horio, J., Satoh, H., Sue, L. I., Beach, T. G., Arita, S., Tooyama, I., & Konishi, Y. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-101815 · Cited by 104 · see citing works
Neuroinflammation in Alzheimer’s disease wanes with age
Hoozemans, J. J., Rozemuller, A. J., van Haastert, E. S., Eikelenboom, P., & van Gool, W. A. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-171 · Cited by 100 · see citing works
Aged Non‐Human Primates: An Animal Model of Age‐Associated Neurodegenerative Disease
Price, D. L., Martin, L. J., Sisodia, S. S., Wagster, M. V., Koo, E. H., Walker, L. C., Koliatsos, V. E., & Cork, L. C. (1991) · Brain Pathology · doi:10.1111/j.1750-3639.1991.tb00672.x · Cited by 100 · see citing works
Praprotnik, D., Smith, M. A., Richey, P. L., Vinters, H. V., & Perry, G. L. (1996) · Acta Neuropathologica · doi:10.1007/s004010050420 · Cited by 98 · see citing works
Age-related accumulation of Reelin in amyloid-like deposits
Knuesel, I., Nyffeler, M., Mormède, C., Muhia, M., Meyer, U., Pietropaolo, S., Yee, B. K., Pryce, C. R., LaFerla, F. M., Marighetto, A., et al. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.08.011 · Cited by 94 · see citing works
Self-citationMcGeer, P. L., Akiyama, H., Kawamata, T., Yamada, T., Walker, D. G., & Ishii, T. (1992) · Journal of Neuroscience Research · doi:10.1002/jnr.490310305 · Cited by 90 · see citing works
Anisman, H., Gibb, J., & Hayley, S. P. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1166-z · Cited by 83 · see citing works
Cathepsin D-mediated proteolysis of apolipoprotein E: Possible role in Alzheimer’s disease
Zhou, W., Scott, S. A., Shelton, S. B., & Crutcher, K. A. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.08.019 · Cited by 82 · see citing works
Maarouf, C. L., Daugs, I. D., Kokjohn, T. A., Walker, D. G., Hunter, J. M., Kruchowsky, J., Woltjer, R. L., Kaye, J. A., Castaño, E. M., Sabbagh, M. N., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027291 · Cited by 80 · see citing works
Expression of amyloid precursor protein after rat traumatic brain injury
Itoh, T., Satou, T., Nishida, S., Tsubaki, M., Hashimoto, S., & Ito, H. (2009) · Neurological Research · doi:10.1179/016164108x323771 · Cited by 78 · see citing works
Gavilán, M. P., Revilla, E., Pintado, C., Castaño, A., Vizuete, M., Moreno‐González, I., Baglietto‐Vargas, D., Sanchez-Varo, R. M., Vitórica, J., Gutiérrez, A., et al. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04787.x · Cited by 77 · see citing works
Schechter, I., & Ziv, E. (2011) · Biological Chemistry · doi:10.1515/bc.2011.054 · Cited by 75 · see citing works
Plasma Aβ42 correlates positively with increased body fat in healthy individuals
Balakrishnan, K., Verdile, G., Mehta, P. D., Beilby, J. P., Nolan, D. A., Galvao, D. A., Newton, R. U., Gandy, S., & Martins, R. N. (2005) · Journal of Alzheimer s Disease · doi:10.3233/jad-2005-8305 · Cited by 74 · see citing works
Tau‐Induced Traffic Jams Reflect Organelles Accumulation at Points of Microtubule Polar Mismatching
Shemesh, O. A., Erez, H., Ginzburg, I., & Spira, M. E. (2007) · Traffic · doi:10.1111/j.1600-0854.2007.00695.x · Cited by 72 · see citing works
Ichihara, N., Wu, J., Hua Chui, D., Yamazaki, K., Wakabayashi, T., & Kikuchi, T. (1995) · Brain Research · doi:10.1016/0006-8993(95)00729-a · Cited by 70 · see citing works
Pintado, C., Gavilán, M. P., Gavilán, E., García-Cuervo, L., Gutiérrez, A., Vitórica, J., Castaño, A., Rios, R. M., & Ruano, D. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-87 · Cited by 63 · see citing works
The Role of Variation at AβPP, PSEN1, PSEN2, and MAPT in Late Onset Alzheimer's Disease
Gerrish, A., Russo, G., Richards, A. L., Moskvina, V., Ivanov, D. K., Harold, D. H., Sims, R., Abraham, R., Hollingworth, P., Chapman, J., et al. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110824 · Cited by 61 · see citing works
アルツハイマー病の再検討:アミロイド-ベータタンパク質前駆体およびアミロイド-ベータの保護的役割の証拠
Ma, S., Perry, G., Xw, Z., Nakamura, M., Hayashi, T., Nunomura, A., Sl, S., Hg, L., & Castellani, R. (2009) · Journal of Alzheimers Disease · Cited by 61 · see citing works
Fiala, J. C., Feinberg, M. D., Peters, A., & Barbas, H. (2007) · Brain Structure and Function · doi:10.1007/s00429-007-0153-1 · Cited by 60 · see citing works
Morales‐Corraliza, J., Mazzella, M. J., Berger, J. D., Diaz, N. S., Choi, J. H. K., Levy, E., Matsuoka, Y., Planel, E., & Mathews, P. M. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007134 · Cited by 59 · see citing works
Immune and behavioral consequences of microglial reactivity in the aged brain
Wynne, A. M., Henry, C. J., & Godbout, J. P. (2009) · Integrative and Comparative Biology · doi:10.1093/icb/icp009 · Cited by 58 · see citing works
Occurrence of HLA‐DR Reactive Microglia in Alzheimer's Disease
McGEER, P. L., ITAGAKI, S., TAGO, H., & McGEER, E. G. (1988) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1988.tb27086.x · Cited by 57 · see citing works
Enhanced -secretase processing alters APP axonal transport and leads to axonal defects
Rodrigues, E. M., Weissmiller, A. M., & Goldstein, L. S. B. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds297 · Cited by 55 · see citing works
Allergy influences the inflammatory status of the brain and enhances tau‐phosphorylation
Sarlus, H., Höglund, C. O., Karshikoff, B., Wang, X., Lekander, M., Schultzberg, M., & Oprica, M. (2012) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2012.01556.x · Cited by 48 · see citing works
Schmidt, M. L., Didario, A. G., Lee, V. M. ‐., & Trojanowski, J. Q. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)00259-2 · Cited by 47 · see citing works
Doehner, J., Madhusudan, A., Konietzko, U., Fritschy, J., & Knuesel, I. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-1333 · Cited by 43 · see citing works
Self-citationXiao, A.-W., He, J., Wang, Q., Luo, Y., Sun, Y., Zhou, Y., Yang, G., Lucassen, P. J., & Dai, J. (2011) · Neuroscience Bulletin · doi:10.1007/s12264-011-1736-7 · Cited by 36 · see citing works
Yilmazer‐Hanke, D., & Hanke, J. (1999) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000017104 · Cited by 36 · see citing works
Extrusion of misfolded and aggregated proteins – a protective strategy of aging neurons?
Doehner, J., Genoud, C., Imhof, C., Krstic, D., & Knuesel, I. (2012) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2012.08154.x · Cited by 36 · see citing works
Self-citationInflammatory Proteins in Plasma and the Risk of Dementia: The Rotterdam Study
Engelhart, M. J., Geerlings, M. I., Meijer, J., Kiliaan, A., Ruitenberg, A., van Swieten, J. C., Stijnen, T., Hofman, A., Witteman, J. C. M., & Breteler, M. M. B. (2004) · Archives of Neurology · doi:10.1001/archneur.61.5.668 · Cited by 10 · see citing works
Immunolocalization of the amyloid precursor protein within the senile plaque.
Perry, G. L., Siedlak, S., Mulvihill, P., et al. (1989) · PubMed · Cited by 6 · see citing works
Aisen, P. S., Schafer, K. A., Grundman, M., Pfeiffer, E., Sano, M., Davis, K. L., Farlow, M. R., Jin, S., Thomas, R. G., Thal, L. J., et al. (2003) · JAMA · doi:10.1001/jama.289.21.2819 · Cited by 5 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Malamud, N. & Hirano, A. Atlas of Neuropathology 2 nd edn 314-327 (University of California Press, Berkley, Los Angeles, London, 1974).
Cited by
Sorted by citations
Immune attack: the role of inflammation in Alzheimer disease
Heppner, F. L., Ransohoff, R. M., & Becher, B. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3880 · Cited by 2,134 · see citing works
Clearance systems in the brain—implications for Alzheimer disease
Tarasoff-Conway, J. M., Carare, R. O., Osorio, R. S., Glodzik, L., Butler, T., Fieremans, E., Axel, L., Rusinek, H., Nicholson, C., Zlokovic, B. V., et al. (2015) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.119 · Cited by 1,678 · see citing works
The Biology of Proteostasis in Aging and Disease
Labbadia, J., & Morimoto, R. I. (2015) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060614-033955 · Cited by 1,472 · see citing works
A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease
Panza, F., Lozupone, M., Logroscino, G., & Imbimbo, B. P. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-018-0116-6 · Cited by 965 · see citing works
Maternal immune activation and abnormal brain development across CNS disorders
Knuesel, I., Chicha, L., Britschgi, M., Schobel, S. A., Bodmer, M., Hellings, J. A., Toovey, S., & Prinssen, E. P. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2014.187 · Cited by 880 · see citing works
Self-citationThe case for rejecting the amyloid cascade hypothesis
Herrup, K. (2015) · Nature Neuroscience · doi:10.1038/nn.4017 · Cited by 768 · see citing works
Microglial dysfunction in brain aging and Alzheimer's disease
Mosher, K. I., & Wyss-Coray, T. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.01.008 · Cited by 618 · see citing works
The Infectious Etiology of Alzheimer’s Disease
Sochocka, M., Zwolińska, K., & Leszek, J. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170313122937 · Cited by 399 · see citing works
A novel Alzheimer disease locus located near the gene encoding tau protein
Jun, G., Ibrahim-Verbaas, C. A., Vronskaya, M., Lambert, J.-C., Chung, J., Naj, A. C., Kunkle, B. W., Wang, L.-S., Bis, J. C., Bellenguez, C., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.23 · Cited by 297 · see citing works
New Insights on <i>NOX</i> Enzymes in the Central Nervous System
Nayernia, Z., Jaquet, V., & Krause, K.-H. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5703 · Cited by 279 · see citing works
Immune hyperreactivity of Aβ plaque-associated microglia in Alzheimer's disease
Yin, Z., Raj, D., Saiepour, N., Van Dam, D., Brouwer, N., Holtman, I. R., Eggen, B. J. L., Möller, T., Tamm, J. A., Abdourahman, A., et al. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.03.021 · Cited by 238 · see citing works
Pathogenesis of synaptic degeneration in Alzheimer's disease and Lewy body disease
Overk, C. R., & Masliah, E. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.01.015 · Cited by 242 · see citing works
Cunningham, C., & Hennessy, E. (2015) · Alzheimer's Research & Therapy · doi:10.1186/s13195-015-0117-2 · Cited by 211 · see citing works
Migration of neutrophils targeting amyloid plaques in Alzheimer's disease mouse model
Baik, S. H., Cha, M.-Y., Hyun, Y.-M., Cho, H., Hamza, B., Kim, D. K., Han, S.-H., Choi, H., Kim, K. H., Moon, M., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.01.003 · Cited by 181 · see citing works
Increased White Matter Inflammation in Aging- and Alzheimer’s Disease Brain
Raj, D., Yin, Z., Breur, M., Doorduin, J., Holtman, I. R., Olah, M., Mantingh-Otter, I. J., Van Dam, D., De Deyn, P. P., den Dunnen, W., et al. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00206 · Cited by 180 · see citing works
Amyloid‐β immunotherapy for alzheimer disease: Is it now a long shot?
Panza, F., Lozupone, M., Seripa, D., & Imbimbo, B. P. (2019) · Annals of Neurology · doi:10.1002/ana.25410 · Cited by 178 · see citing works
The Possibility of an Infectious Etiology of Alzheimer Disease
Ashraf, G. M., Tarasov, V. V., Makhmutovа, A., Chubarev, V. N., Avila-Rodriguez, M., Bachurin, S. O., & Aliev, G. (2019) · Molecular Neurobiology · doi:10.1007/s12035-018-1388-y · Cited by 175 · see citing works
Local and distant relationships between amyloid, tau and neurodegeneration in Alzheimer's Disease
Iaccarino, L., Tammewar, G., Ayakta, N., Baker, S. L., Bejanin, A., Boxer, A. L., Gorno-Tempini, M. L., Janabi, M., Kramer, J. H., Lazaris, A., et al. (2018) · NeuroImage: Clinical · doi:10.1016/j.nicl.2017.09.016 · Cited by 165 · see citing works
Animal models of Alzheimer’s disease: Applications, evaluation, and perspectives
Chen, Z.-Y., 北京大学生命科学学院膜生物学国家重点实验室, 北. 1., State Key Laboratory of Membrane Biology, C. O. L. S., & Zhang, Y. (2022) · Zoological Research · doi:10.24272/j.issn.2095-8137.2022.289 · Cited by 155 · see citing works
Quantitative proteomics reveals distinct composition of amyloid plaques in Alzheimer’s disease
Xiong, F., Ge, W., & Ma, C. (2019) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.10.006 · Cited by 133 · see citing works
Deardorff, W. J., & Grossberg, G. (2016) · Drug Design, Development and Therapy · doi:10.2147/dddt.s86463 · Cited by 125 · see citing works
Polymicrobial Infections In Brain Tissue From Alzheimer’s Disease Patients
Pisa, D., Alonso, R., Fernández-Fernández, A. M., Rábano, A., & Carrasco, L. (2017) · Scientific Reports · doi:10.1038/s41598-017-05903-y · Cited by 114 · see citing works
Agosta, F., Dalla Libera, D., Spinelli, E. G., Finardi, A., Canu, E., Bergami, A., Bocchio Chiavetto, L., Baronio, M., Comi, G., Martino, G., et al. (2014) · Annals of Neurology · doi:10.1002/ana.24235 · Cited by 113 · see citing works
Clearance of Amyloid-Beta in Alzheimer’s Disease: Shifting the Action Site from Center to Periphery
Liu, Y.-H., Wang, Y.-R., Xiang, Y., Zhou, H.-D., Giunta, B., Mañucat-Tan, N. B., Tan, J., Zhou, X.-F., & Wang, Y.-J. (2015) · Molecular Neurobiology · doi:10.1007/s12035-014-8694-9 · Cited by 99 · see citing works
Nasiri, E., Sankowski, R., Dietrich, H., Oikonomidi, A., Huerta, P. T., Popp, J., Al-Abed, Y., & Bacher, M. (2020) · Molecular Medicine · doi:10.1186/s10020-020-00163-5 · Cited by 91 · see citing works
Zhang, C., Griciuc, A., Hudry, E., Wan, Y., Quinti, L., Ward, J., Forte, A. M., Shen, X., Ran, C., Elmaleh, D. R., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-19641-2 · Cited by 99 · see citing works
Hargis, K. E., & Blalock, E. M. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.05.007 · Cited by 90 · see citing works
Hoeijmakers, L., Heinen, Y., van Dam, A.-M., Lucassen, P. J., & Korosi, A. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00398 · Cited by 85 · see citing works
NRBF2 is involved in the autophagic degradation process of APP-CTFs in Alzheimer disease models
Yang, C., Cai, C.-Z., Song, J.-X., Tan, J.-Q., Durairajan, S. S. K., Iyaswamy, A., Wu, M.-Y., Chen, L.-L., Yue, Z., Li, M., et al. (2017) · Autophagy · doi:10.1080/15548627.2017.1379633 · Cited by 83 · see citing works
Imaging of cerebrovascular pathology in animal models of Alzheimer's disease
Klohs, J., Rudin, M., Shimshek, D. R., & Beckmann, N. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00032 · Cited by 82 · see citing works
Lalli, M. A., Bettcher, B. M., Arcila, M. L., Garcia, G., Guzman, C., Madrigal, L., Ramirez, L., Acosta-Uribe, J., Baena, A., Wojta, K. J., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2015.131 · Cited by 73 · see citing works
Anti-amyloid-β protein agents for the treatment of Alzheimer’s disease: an update on emerging drugs
Lozupone, M., Solfrizzi, V., D’Urso, F., Di Gioia, I., Sardone, R., Dibello, V., Stallone, R., Liguori, A., Ciritella, C., Daniele, A., et al. (2020) · Expert Opinion on Emerging Drugs · doi:10.1080/14728214.2020.1808621 · Cited by 77 · see citing works
Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration
van Dijk, G., van Heijningen, S., Reijne, A. C., Nyakas, C., van der Zee, E. A., & Eisel, U. L. M. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00173 · Cited by 75 · see citing works
Bosch, C., Masachs, N., Exposito-Alonso, D., Martínez, A., Teixeira, C. M., Fernaud, I., Pujadas, L., Ulloa, F., Comella, J. X., DeFelipe, J., et al. (2016) · Cerebral Cortex · doi:10.1093/cercor/bhw216 · Cited by 70 · see citing works
Neuroinflammation in Alzheimer’s disease: Pleiotropic roles for cytokines and neuronal pentraxins
Swanson, A., Wolf, T., Sitzmann, A., & Willette, A. A. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.02.015 · Cited by 72 · see citing works
Daianu, M., Mendez, M. F., Baboyan, V. G., Jin, Y., Melrose, R. J., Jimenez, E. E., & Thompson, P. M. (2016) · Brain Imaging and Behavior · doi:10.1007/s11682-015-9458-5 · Cited by 64 · see citing works
The Oral Microbiome and Inflammation in Mild Cognitive Impairment
Yang, I., Arthur, R. A., Zhao, L., Clark, J., Hu, Y., Corwin, E. J., & Lah, J. (2021) · Experimental Gerontology · doi:10.1016/j.exger.2021.111273 · Cited by 56 · see citing works
The Role of Amyloid-Beta and Tau in the Early Pathogenesis of Alzheimer’s Disease
Yin, X., Qiu, Y., Zhao, C., Zhou, Z., Bao, J., & Qian, W. (2021) · Medical Science Monitor · doi:10.12659/msm.933084 · Cited by 48 · see citing works
Early and sustained altered expression of aging-related genes in young 3xTg-AD mice
Gatta, V, D'Aurora, M., Granzotto, A., Stuppia, L., & Sensi, S. L. (2014) · Cell Death & Disease · doi:10.1038/cddis.2014.11 · Cited by 44 · see citing works
Herzer, S., Hagan, C., von Gerichten, J., Dieterle, V., Munteanu, B., Sandhoff, R., Hopf, C., & Nordström, V. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00206 · Cited by 27 · see citing works
Alzheim(i)R: MicroRNAs in Alzheimer’s Disease
Barbato, C. (2014) · Journal of Cytology & Histology · doi:10.4172/2157-7099.1000e113 · Cited by 3 · see citing works
- Authors
- Krstic, D., & Knuesel, I.
- Affiliations
- University of Zurich (CH)
- Venue
- Nature Reviews Neurology
- Published
- 2012-11-27
- Volume
- 9
- Issue
- 1
- Pages
- 25-34
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- OpenAlex
- W1964117773
- Cited by
- 457
- References
- 143
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 23 · 2023: 23 · 2022: 31 · 2021: 35 · 2020: 27 · 2019: 35 · 2018: 41 · 2017: 47 · 2016: 54 · 2015: 49 · 2014: 52 · 2013: 20 · 2012: 1
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Neurology (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Science Foundation (310030)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (132629, 310030)
- Olga Mayenfisch Stiftung
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- late-onset Alzheimer's disease, amyloid-beta, tau hyperphosphorylation, neuroinflammation, axonal integrity, axonal transport, mitochondrial accumulation, neurofibrillary tangles, neurite degeneration, amyloid precursor protein, drug development failure
- MeSH terms
- Aged, Alzheimer Disease, Animals, Brain, Disease Models, Animal, Humans, Amyloid beta-Peptides, Neurites, Neurofibrillary Tangles, tau Proteins, Cell Death, Disease Progression, Inflammation Mediators, Mice, Proteostasis Deficiencies
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
