Autophagic and lysosomal defects in human tauopathies: analysis of post-mortem brain from patients with familial Alzheimer disease, corticobasal degeneration and progressive supranuclear palsy
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INTRODUCTION: The accumulation of insoluble proteins within neurons and glia cells is a pathological hallmark of several neurodegenerative diseases. Abnormal aggregation of the microtubule-associated protein tau characterizes the neuropathology of tauopathies, such as Alzheimer disease (AD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). An impairment of the lysosomal degradation pathway called macroautophagy, hereafter referred to as autophagy, could contribute to the accumulation of aggregated proteins. The role of autophagy in neurodegeneration has been intensively studied in the context of AD but there are few studies in other tauopathies and it is not known if defects in autophagy is a general feature of tauopathies. In the present study, we analysed autophagic and lysosomal markers in human post-mortem brain samples from patients with early-onset familial AD (FAD) with the APP Swedish mutation (APPswe), CBD and PSP and control individuals. RESULTS: FAD, CBD and PSP patients displayed an increase in LC3-positive vesicles in frontal cortex, indicating an accumulation of autophagic vesicles. Moreover, using double-immunohistochemistry and in situ proximity ligation assay, we observed colocalization of hyperphosphorylated tau with the autophagy marker LC3 in FAD, CBD and PSP patients but not in control individuals. Increased levels of the lysosomal marker LAMP1 was detected in FAD and CBD, and in addition Cathepsin D was diffusely spread in the cytoplasm in all tauopathies suggesting an impaired lysosomal integrity. CONCLUSION: Taken together, our results indicate an accumulation of autophagic and lysosomal markers in human brain tissue from patients with primary tauopathies (CBD and PSP) as well as FAD, suggesting a defect of the autophagosome-lysosome pathway that may contribute to the development of tau pathology.
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Disruption of the autophagy-lysosomal pathway is a pathological hallmark in human tauopathy brain.
“Disruption of the autophagy-lysosomal pathway (ALP) is another pathological hallmark in human tauopathy brain (Bain et al., 2019; Piras et al., 2016; Wang et al., 2009).”
From ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids (2021) · cites this paper as Piras et al., 2016
Disruption of autophagic flux and failure of autophagosomes to fuse with lysosomes leads to a build-up of vesicles seen in dystrophic neurites and cell bodies in AD, CBD and PSP, as well as in tauopathy models.
“Disruption of autophagic flux and a failure of autophagosomes to fuse with lysosomes leads to a build-up of vesicles, which can be seen in dystrophic neurites and cell bodies in AD, CBD and PSP, as well as in tauopathy models73–76.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [76]
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Pankiv, S., Clausen, T. H., Lamark, T., Brech, A., Bruun, J.-A., Outzen, H., Øvervatn, A., Bjørkøy, G., & Johansen, T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702824200 · Cited by 4,578 · see citing works
Guidelines for the use and interpretation of assays for monitoring autophagy
Klionsky, D. J., Abdalla, F. C., Abeliovich, H., Abraham, R. T., Acevedo-Arozena, A., Adeli, K., Agholme, L., Agnello, M., Agostinis, P., Aguirre-Ghiso, J. A., et al. (2012) · Autophagy · doi:10.4161/auto.19496 · Cited by 3,996 · cited 5× · see citing works
“In order to achieve degradation of aggregated proteins in the autophagy-lysosome system, there must be a successful fusion of the autophagosomes with the lysosomes [17, 18, 29, 36, 73].”
BackgroundInfluentialSelf-citationSuppression of basal autophagy in neural cells causes neurodegenerative disease in mice
Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., et al. (2006) · Nature · doi:10.1038/nature04724 · Cited by 3,882 · see citing works
Autophagy as a regulated pathway of cellular degradation.
Klionsky, D., & Emr, S. (2000) · Science · doi:10.1126/science.290.5497.1717 · Cited by 3,794 · see citing works
Grundke-Iqbal, I., Iqbal, K., Tung, Y. C., Quinlan, M., Wisniewski, H. M., & Binder, L. I. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.13.4913 · Cited by 3,676 · see citing works
Regulation mechanisms and signaling pathways of autophagy
He, C., & Klionsky, D. J. (2009) · Annual Review of Genetics · doi:10.1146/annurev-genet-102808-114910 · Cited by 3,609 · see citing works
Loss of autophagy in the central nervous system causes neurodegeneration in mice
Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J.-I., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E., et al. (2006) · Nature · doi:10.1038/nature04723 · Cited by 3,500 · see citing works
A protein factor essential for microtubule assembly
Weingarten, M. D., Lockwood, A. H., Hwo, S. Y., & Kirschner, M. W. (1975) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.72.5.1858 · Cited by 3,089 · see citing works
Direct observation of individual endogenous protein complexes in situ by proximity ligation
Söderberg, O., Gullberg, M., Jarvius, M., Ridderstråle, K., Leuchowius, K.-J., Jarvius, J., Wester, K., Hydbring, P., Bahram, F., Larsson, L.-G., et al. (2006) · Nature Methods · doi:10.1038/nmeth947 · Cited by 2,419 · see citing works
Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders
Ballatore, C., Lee, V. M.-Y., & Trojanowski, J. Q. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2194 · Cited by 2,174 · see citing works
Autophagosome formation: core machinery and adaptations
Xie, Z., & Klionsky, D. J. (2007) · Nature Cell Biology · doi:10.1038/ncb1007-1102 · Cited by 2,165 · see citing works
Eaten alive: a history of macroautophagy
Yang, Z., & Klionsky, D. J. (2010) · Nature Cell Biology · doi:10.1038/ncb0910-814 · Cited by 2,096 · see citing works
The role of autophagy in neurodegenerative disease
Nixon, R. A. (2013) · Nature Medicine · doi:10.1038/nm.3232 · Cited by 2,059 · see citing works
Mammalian autophagy: core molecular machinery and signaling regulation
Yang, Z., & Klionsky, D. J. (2010) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.11.014 · Cited by 1,956 · 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
Lysosomal membrane permeabilization in cell death
Boya, P., & Kroemer, G. (2008) · Oncogene · doi:10.1038/onc.2008.310 · Cited by 1,425 · see citing works
Yamamoto, A., Tagawa, Y., Yoshimori, T., Moriyama, Y., Masaki, R., & Tashiro, Y. (1998) · Cell Structure and Function · doi:10.1247/csf.23.33 · Cited by 1,312 · see citing works
Lee, J.-H., Yu, W. H., Kumar, A., Lee, S., Mohan, P. S., Peterhoff, C. M., Wolfe, D. M., Martinez-Vicente, M., Massey, A. C., Sovak, G., et al. (2010) · Cell · doi:10.1016/j.cell.2010.05.008 · Cited by 1,212 · see citing works
Boland, B., Kumar, A., Lee, S., Platt, F. M., Wegiel, J., Yu, W. H., & Nixon, R. A. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0800-08.2008 · Cited by 1,119 · see citing works
Mandelkow, E., & Mandelkow, E. (1998) · Trends in Cell Biology · doi:10.1016/s0962-8924(98)01368-3 · Cited by 951 · see citing works
Studies on the mechanisms of autophagy: formation of the autophagic vacuole.
Dunn, W. A. (1990) · The Journal of Cell Biology · doi:10.1083/jcb.110.6.1923 · Cited by 787 · see citing works
Autophagy, amyloidogenesis and Alzheimer disease
Nixon, R. A. (2007) · Journal of Cell Science · doi:10.1242/jcs.019265 · Cited by 749 · see citing works
Seibenhener, M. L., Babu, J. R., Geetha, T., Wong, H. C., Krishna, N. R., & Wooten, M. W. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.18.8055-8068.2004 · Cited by 710 · see citing works
Lipinski, M. M., Zheng, B., Lu, T., Yan, Z., Py, B. F., Ng, A., Xavier, R. J., Li, C., Yankner, B. A., Scherzer, C. R., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009485107 · Cited by 680 · see citing works
Tau fragmentation, aggregation and clearance: the dual role of lysosomal processing
Wang, Y., Martinez-Vicente, M., Krüger, U., Kaushik, S., Wong, E., Mandelkow, E.-M., Cuervo, A. M., & Mandelkow, E. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp367 · Cited by 617 · see citing works
Morris, M., Knudsen, G. M., Maeda, S., Trinidad, J. C., Ioanoviciu, A., Burlingame, A. L., & Mucke, L. (2015) · Nature Neuroscience · doi:10.1038/nn.4067 · Cited by 472 · 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
Dynein-dependent Movement of Autophagosomes Mediates Efficient Encounters with Lysosomes
Kimura, S., Noda, T., & Yoshimori, T. (2008) · Cell Structure and Function · doi:10.1247/csf.08005 · Cited by 434 · see citing works
Cataldo, A. M., Barnett, J. L., Berman, S. A., Li, J., Quarless, S., Bursztajn, S., Lippa, C., & Nixon, R. A. (1995) · Neuron · doi:10.1016/0896-6273(95)90324-0 · Cited by 379 · see citing works
Tau degradation: The ubiquitin–proteasome system versus the autophagy-lysosome system
Lee, M. J., Lee, J. H., & Rubinsztein, D. C. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.03.001 · Cited by 364 · see citing works
Caccamo, A., Magrì, A., Medina, D. X., Wisely, E. V., López‐Aranda, M. F., Silva, A. J., & Oddo, S. (2013) · Aging Cell · doi:10.1111/acel.12057 · Cited by 362 · see citing works
Studies on the mechanisms of autophagy: maturation of the autophagic vacuole.
Dunn, W. A. (1990) · The Journal of Cell Biology · doi:10.1083/jcb.110.6.1935 · Cited by 362 · see citing works
Autophagy failure in A lzheimer's disease and the role of defective lysosomal acidification
Wolfe, D. M., Lee, J., Kumar, A. R., Lee, S., Orenstein, S. J., & Nixon, R. A. (2013) · European Journal of Neuroscience · doi:10.1111/ejn.12169 · Cited by 348 · see citing works
Kuusisto, E., Salminen, A., & Alafuzoff, I. I. (2001) · Neuroreport · doi:10.1097/00001756-200107200-00009 · Cited by 347 · see citing works
Stimulation of autophagy reduces neurodegeneration in a mouse model of human tauopathy
Schaeffer, V., Lavenir, I., Ozcelik, S., Tolnay, M., Winkler, D. T., & Goedert, M. (2012) · Brain · doi:10.1093/brain/aws143 · Cited by 343 · see citing works
p62/SQSTM1: A Missing Link between Protein Aggregates and the Autophagy Machinery
Bjørkøy, G., Lamark, T., & Johansen, T. (2006) · Autophagy · doi:10.4161/auto.2.2.2405 · Cited by 322 · see citing works
Autophagy in neurodegenerative disease: friend, foe or turncoat?
Nixon, R. A. (2006) · Trends in Neurosciences · doi:10.1016/j.tins.2006.07.003 · Cited by 315 · see citing works
Sequestosome 1/p62 shuttles polyubiquitinated tau for proteasomal degradation
Babu, J. R., Geetha, T., & Wooten, M. W. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03181.x · Cited by 315 · see citing works
Autophagic degradation of tau in primary neurons and its enhancement by trehalose
Krüger, U., Wang, Y., Kumar, S., & Mandelkow, E.-M. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.11.009 · Cited by 297 · see citing works
The lysosomal protease cathepsin D mediates apoptosis induced by oxidative stress
Kågedal, K., Johansson, U., & Öllinger, K. M. (2001) · The FASEB Journal · doi:10.1096/fj.00-0708fje · Cited by 281 · see citing works
Yu, W. H., Kumar, A., Peterhoff, C., Shapiro Kulnane, L., Uchiyama, Y., Lamb, B. T., Cuervo, A. M., & Nixon, R. A. (2004) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2004.05.010 · Cited by 279 · see citing works
Cataldo, A. M., Paskevich, P. A., Kominami, E., & Nixon, R. A. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.24.10998 · Cited by 267 · see citing works
Hernández, F., & Ávila, J. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-7220-x · Cited by 263 · see citing works
Rapamycin attenuates the progression of tau pathology in P301S tau transgenic mice.
Ozcelik, S., Fraser, G., Castets, P., Schaeffer, V., Skachokova, Z., Breu, K., Clavaguera, F., Sinnreich, M., Kappos, L., Goedert, M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062459 · Cited by 226 · see citing works
Cataldo, A., Hamilton, D. J., & Nixon, R. (1994) · Brain Research · doi:10.1016/0006-8993(94)91858-9 · Cited by 225 · see citing works
Tau clearance mechanisms and their possible role in the pathogenesis of Alzheimer disease.
Chesser, A. S., Pritchard, S. M., & Johnson, G. V. W. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00122 · Cited by 219 · see citing works
Kuusisto, E., Salminen, A., & Alafuzoff, I. I. (2002) · Neuropathology and Applied Neurobiology · doi:10.1046/j.1365-2990.2002.00394.x · Cited by 213 · see citing works
Liu, Z., Li, T., Li, P., Wei, N., Zhao, Z., Liang, H., Ji, X., Chen, W., Xue, M., & Wei, J. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/352723 · Cited by 208 · see citing works
Collin, L., Bohrmann, B., Göpfert, U., Oroszlan‐Szovik, K., Ozmen, L., & Grüninger, F. (2014) · Brain · doi:10.1093/brain/awu213 · Cited by 203 · see citing works
Self-citationAutophagic/lysosomal dysfunction in Alzheimer’s disease
Orr, M. E., & Oddo, S. (2013) · Alzheimer's Research & Therapy · doi:10.1186/alzrt217 · Cited by 199 · see citing works
The role of lysosomal rupture in neuronal death
Yamashima, T., & Oikawa, S. (2009) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2009.09.003 · Cited by 183 · see citing works
Guillozet-Bongaarts, A. L., Cahill, M. E., Cryns, V. L., Reynolds, M. R., Berry, R. W., & Binder, L. I. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03784.x · Cited by 169 · see citing works
Macroautophagy deficiency mediates age-dependent neurodegeneration through a phospho-tau pathway
Inoue, K., Rispoli, J., Kaphzan, H., Klann, E., Chen, E. I., Kim, J., Komatsu, M., & Abeliovich, A. (2012) · Molecular Neurodegeneration · doi:10.1186/1750-1326-7-48 · Cited by 168 · see citing works
Degradation of tau protein by autophagy and proteasomal pathways
Wang, Y., & Mandelkow, E. (2012) · Biochemical Society Transactions · doi:10.1042/bst20120071 · Cited by 166 · see citing works
The lysosome and neurodegenerative diseases
Zhang, L., Sheng, R., & Qin, Z. (2009) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmp031 · Cited by 156 · see citing works
A Caspase Cleaved Form of Tau Is Preferentially Degraded through the Autophagy Pathway
Dolan, P. J., & Johnson, G. V. W. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.110940 · Cited by 147 · see citing works
Autophagic vacuoles rapidly fuse with pre-existing lysosomes in cultured hepatocytes
Lawrence, B. P., & Brown, W. J. (1992) · Journal of Cell Science · doi:10.1242/jcs.102.3.515 · Cited by 127 · see citing works
Ultrastructural neuronal pathology in transgenic mice expressing mutant (P301L) human tau
Lin, W.-L., Lewis, J. M., Yen, S.-H. C., Hutton, M. L., & Dickson, D. W. (2003) · Journal of Neurocytology · doi:10.1023/b:neur.0000021904.61387.95 · Cited by 125 · see citing works
Mammalian Target of Rapamycin (mTor) Mediates Tau Protein Dyshomeostasis
Tang, Z., Bereczki, E., Zhang, H., Wang, S., Li, C., Ji, X., Branca, R. M., Lehtiö, J., Guan, Z., Filipčík, P., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.435123 · Cited by 124 · see citing works
Use of p62/SQSTM1 antibodies for neuropathological diagnosis
Kuusisto, E., Kauppinen, T., & Alafuzoff, I. I. (2007) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2007.00884.x · Cited by 113 · see citing works
Abnormal distribution of cathepsins in the brain of patients with Alzheimer's disease
Nakamura, Y., Takeda, M., Suzuki, H., Hattori, H., Tada, K., Hariguchi, S., Hashimoto, S., & Nishimura, T. (1991) · Neuroscience Letters · doi:10.1016/0304-3940(91)90395-a · Cited by 111 · see citing works
The Lysosomal System in Neurons
Nixon, R., Cataldo, A., Paskevich, P., Hamilton, D. J., Wheelock, T. R., & Kanaley-Andrews, L. (1992) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1992.tb27478.x · Cited by 97 · see citing works
Lysosome‐associated membrane protein 1 (LAMP‐1) in Alzheimer’s disease
Barrachina, M., Maes, T., Buesa, C., & Ferrer, I. (2006) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2006.00756.x · Cited by 97 · see citing works
Sato-Harada, R., Okabe, S., Umeyama, T., Kanai, Y., & Hirokawa, N. (1996) · Cell Structure and Function · doi:10.1247/csf.21.283 · Cited by 97 · see citing works
Aits, S., Jäättelä, M., & Nylandsted, J. (2015) · Methods in cell biology · doi:10.1016/bs.mcb.2014.10.032 · Cited by 95 · see citing works
Fast Axonal Transport Misregulation and Alzheimer's Disease
Morfini, G. A., Pigino, G. F., Beffert, U., Busciglio, J. A., & Brady, S. T. (2002) · NeuroMolecular Medicine · doi:10.1385/nmm:2:2:089 · Cited by 94 · see citing works
Roberg, K. B. (2001) · Laboratory Investigation · doi:10.1038/labinvest.3780222 · Cited by 91 · see citing works
Gentry, E. G., Henderson, B. W., Arrant, A. E., Gearing, M., Feng, Y., Riddle, N. C., & Herskowitz, J. H. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.2336-15.2016 · Cited by 90 · see citing works
Cataldo, A., Barnett, J. L., Mann, D. M. A., & Nixon, R. A. (1996) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199606000-00004 · Cited by 74 · see citing works
Kim, J., Choi, I.-Y., Michaelis, M. L., & Lee, P. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.02.039 · Cited by 65 · see citing works
In vivo axonal transport deficits in a mouse model of fronto-temporal dementia
Majid, T., Ali, Y., Venkitaramani, D. V., Jang, M., Lu, H., & Pautler, R. G. (2014) · NeuroImage Clinical · doi:10.1016/j.nicl.2014.02.005 · Cited by 65 · see citing works
Hippocampal Endosomal, Lysosomal, and Autophagic Dysregulation in Mild Cognitive Impairment
Perez, S. E., He, B., Nadeem, M., Wuu, J., Ginsberg, S. D., Ikonomović, M. D., & Mufson, E. J. (2015) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000179 · Cited by 57 · see citing works
Inhibition of HDAC6 Modifies Tau Inclusion Body Formation and Impairs Autophagic Clearance
Leyk, J., Goldbaum, O., Noack, M., & Richter‐Landsberg, C. (2014) · Journal of Molecular Neuroscience · doi:10.1007/s12031-014-0460-y · Cited by 49 · see citing works
Modifications in P62 occur due to proteasome inhibition in alcoholic liver disease
Bardag‐Gorce, F., Francis, T., Nan, L., Li, J., Lue, Y., French, B. A., & French, S. W. (2005) · Life Sciences · doi:10.1016/j.lfs.2005.04.020 · Cited by 46 · see citing works
SUMO-1 is Associated with a Subset of Lysosomes in Glial Protein Aggregate Diseases
Wong, M. B., Goodwin, J., Norazit, A., Meedeniya, A. C. B., Richter‐Landsberg, C., Gai, W., & Pountney, D. L. (2012) · Neurotoxicity Research · doi:10.1007/s12640-012-9358-z · Cited by 42 · see citing works
Niewiadomska, G., Baksalerska-Pazera, M., & Riedel, G. (2005) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1342.026 · Cited by 39 · see citing works
Schedin‐Weiss, S., Inoue, M., Teranishi, Y., Yamamoto, N. G., Karlström, H., Winblad, B. G., & Tjernberg, L. O. (2013) · PLoS ONE · doi:10.1371/journal.pone.0063962 · Cited by 15 · see citing works
The Earliest Tau Dysfunction in Alzheimer's Disease?
Voss, K., Koren, J., & Dickey, C. A. (2011) · American Journal Of Pathology · doi:10.1016/j.ajpath.2011.08.020 · Cited by 14 · see citing works
Flagged first, then by citations
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Sorted by citations
Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities
Menzies, F. M., Fleming, A., Caricasole, A., Bento, C. F., Andrews, S. P., Ashkenazi, A., Füllgrabe, J., Jackson, A., Jimenez Sanchez, M., Karabiyik, C., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.01.022 · Cited by 1,134 · see citing works
Tau-targeting therapies for Alzheimer disease
Congdon, E. E., & Sigurdsson, E. M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0013-z · Cited by 1,113 · see citing works
Alquezar, C., Arya, S., & Kao, A. W. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2020.595532 · Cited by 367 · see citing works
Bordi, 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
Molecular signatures underlying neurofibrillary tangle susceptibility in Alzheimer’s disease
Otero-Garcia, M., Mahajani, S. U., Wakhloo, D., Tang, W., Xue, Y.-Q., Morabito, S., Pan, J., Oberhauser, J., Madira, A. E., Shakouri, T., et al. (2022) · Neuron · doi:10.1016/j.neuron.2022.06.021 · Cited by 262 · see citing works
Bowles, K. R., Silva, M. C., Whitney, K., Bertucci, T., Berlind, J. E., Lai, J. D., Garza, J. C., Boles, N. C., Mahali, S., Strang, K. H., et al. (2021) · Cell · doi:10.1016/j.cell.2021.07.003 · Cited by 175 · see citing works
Autophagy Dysfunction in Alzheimer’s Disease: Mechanistic Insights and New Therapeutic Opportunities
Di Meco, A., Curtis, M. E., Lauretti, E., & Praticò, D. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.05.008 · Cited by 133 · see citing works
Lo, C. H., & Zeng, J. (2023) · Translational Neurodegeneration · doi:10.1186/s40035-023-00362-0 · Cited by 117 · see citing works
Targeting autophagy in Alzheimer’s disease: Animal models and mechanisms
Zhang, X.-W., 澳门大学中华医药研究院中药质量研究国家重点实验室, 澳. 凼. 9., State Key Laboratory of Quality Research in Chinese Medicine, I. O. C. M. S., Zhu, X.-X., Tang, D.-S., Lu, J.-H., 佛山大学广东省动物分子设计与精准育种重点实验室, 广., & Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, G. E. T. C. O. G. P. (2023) · Zoological Research · doi:10.24272/j.issn.2095-8137.2023.294 · Cited by 77 · see citing works
“Studies have shown that hyperphosphorylated tau colocalizes with the autophagic marker LC3 and substrate p62/SQSTM1 in the brains of FAD patients and model mice (Piras et al., 2016).”
BackgroundMallucci, G. R., Klenerman, D., & Rubinsztein, D. C. (2020) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-040320-120625 · Cited by 62 · see citing works
Pharmacological modulation of autophagy for Alzheimer's disease therapy: Opportunities and obstacles
Deng, Z., Dong, Y., Zhou, X., Lu, J.-H., & Yue, Z. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.12.009 · Cited by 58 · see citing works
Khezri, M. R., & Ghasemnejad-Berenji, M. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-220873 · Cited by 12 · see citing works
Beaudet, D., Berger, C. L., & Hendricks, A. G. (2026) · eLife · doi:10.7554/elife.110011
- Authors
- Piras, A., Collin, L., Grüninger, F., Graff, C., & Rönnbäck, A.
- Affiliations
- Karolinska Institutet (SE)
- F. Hoffmann-La Roche AG (CH)
- Karolinska University Hospital (SE)
- Corresponding author
- Rönnbäck, Annica
- Venue
- Acta Neuropathologica Communications
- Published
- 2016-03-02
- Volume
- 4
- Issue
- 1
- Pages
- 22-22
- ISSN
- 2051-5960 (ISSN-L)
- PMC
- PMC4774096
- OpenAlex
- W2290722071
- Cited by
- 271
- References
- 78
- Citations by year
- 2026: 27 · 2025: 39 · 2024: 34 · 2023: 29 · 2022: 24 · 2021: 36 · 2020: 31 · 2019: 15 · 2018: 21 · 2017: 10 · 2016: 5
- FWCI
- 13.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Acta Neuropathologica Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- F. Hoffman-La Roche
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tauopathy, autophagy, lysosomal dysfunction, familial Alzheimer's disease, APP Swedish mutation, corticobasal degeneration, progressive supranuclear palsy, hyperphosphorylated tau, LC3, LAMP1, cathepsin D, protein aggregation, postmortem brain
- MeSH terms
- Sequestosome-1 Protein, Aged, Aged, 80 and over, Alzheimer Disease, Autophagy, Brain, Female, Humans, Lysosomes, Male, Microtubule-Associated Proteins, Middle Aged, Nerve Tissue Proteins, Postmortem Changes, Supranuclear Palsy, Progressive, tau Proteins, Neurodegenerative Diseases, Adaptor Proteins, Signal Transducing, Lysosomal-Associated Membrane Protein 1
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