Aβ accumulation causes MVB enlargement and is modelled by dominant negative VPS4A

go back to reference Cataldo AM, Petanceska S, Terio NB, Peterhoff CM, Durham R, Mercken M, Mehta PD, Buxbaum J, Haroutunian V, Nixon RA. Abeta localization in abnormal endosomes: association with earliest Abeta elevations in AD and down syndrome. Neurobiol Aging. 2004;25:1263–72.CrossRefPubMed Cataldo AM, Petanceska S, Terio NB, Peterhoff CM, Durham R, Mercken M, Mehta PD, Buxbaum J, Haroutunian V, Nixon RA. Abeta localization in abnormal endosomes: association with earliest Abeta elevations in AD and down syndrome. Neurobiol Aging. 2004;25:1263–72.CrossRefPubMed

go back to reference D’Andrea MR, Nagele RG, Wang HY, Peterson PA, Lee DHS. Evidence that neurones accumulating amyloid can undergo lysis to form amyloid plaques in Alzheimer’s disease. Histopathology. 2001;38:120–34.CrossRefPubMed D’Andrea MR, Nagele RG, Wang HY, Peterson PA, Lee DHS. Evidence that neurones accumulating amyloid can undergo lysis to form amyloid plaques in Alzheimer’s disease. Histopathology. 2001;38:120–34.CrossRefPubMed

go back to reference Gouras GK, Tsai J, Naslund J, Vincent B, Edgar M, Checler F, Greenfield JP, Haroutunian V, Buxbaum JD, Xu H, Greengard P, Relkin NR. Intraneuronal Ab42 accumulation in human brain. Am J Pathol. 2000;156:15–20.CrossRefPubMedPubMedCentral Gouras GK, Tsai J, Naslund J, Vincent B, Edgar M, Checler F, Greenfield JP, Haroutunian V, Buxbaum JD, Xu H, Greengard P, Relkin NR. Intraneuronal Ab42 accumulation in human brain. Am J Pathol. 2000;156:15–20.CrossRefPubMedPubMedCentral

go back to reference Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J, Guillozet-Bongaarts A, Ohno M, Disterhoft J, Van Eldik L, Berry R, Vassar R. Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer’s disease mutations: potential factors in amyloid plaque formation. J Neurosci. 2006;26:10129–40.CrossRefPubMed Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J, Guillozet-Bongaarts A, Ohno M, Disterhoft J, Van Eldik L, Berry R, Vassar R. Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer’s disease mutations: potential factors in amyloid plaque formation. J Neurosci. 2006;26:10129–40.CrossRefPubMed

go back to reference Takahashi RH, Milner TA, Li F, Nam EE, Edgar MA, Yamaguchi H, Beal MF, Xu H, Greengard P, Gouras GK. Intraneuronal Alzheimer Abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology. Am J Pathol. 2002;161:1869–79.CrossRefPubMedPubMedCentral Takahashi RH, Milner TA, Li F, Nam EE, Edgar MA, Yamaguchi H, Beal MF, Xu H, Greengard P, Gouras GK. Intraneuronal Alzheimer Abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology. Am J Pathol. 2002;161:1869–79.CrossRefPubMedPubMedCentral

go back to reference Wirths O, Multhaup G, Czech C, Blanchard V, Moussaoui S, Tremp G, Pradier L, Beyreuther K, Bayer TA. Intraneuronal Abeta accumulation precedes plaque formation in beta-amyloid precursor protein and presenilin-1 double-transgenic mice. Neurosci Lett. 2001;306:116–20.CrossRefPubMed Wirths O, Multhaup G, Czech C, Blanchard V, Moussaoui S, Tremp G, Pradier L, Beyreuther K, Bayer TA. Intraneuronal Abeta accumulation precedes plaque formation in beta-amyloid precursor protein and presenilin-1 double-transgenic mice. Neurosci Lett. 2001;306:116–20.CrossRefPubMed

go back to reference Billings LM, Oddo S, Green KN, McGaugh JL, LaFerla FM. Intraneuronal Abeta causes the onset of early Alzheimer’s disease-related cognitive deficits in transgenic mice. Neuron. 2005;45:675–88.CrossRefPubMed Billings LM, Oddo S, Green KN, McGaugh JL, LaFerla FM. Intraneuronal Abeta causes the onset of early Alzheimer’s disease-related cognitive deficits in transgenic mice. Neuron. 2005;45:675–88.CrossRefPubMed

go back to reference Chapman PF, White GL, Jones MW, Cooper-Blacketer D, Marshall VJ, Irizarry M, Younkin L, Good MA, Bliss TV, Hyman BT, Younkin SG, Hsiao KK. Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice. Nat Neurosci. 1999;2:271–6.CrossRefPubMed Chapman PF, White GL, Jones MW, Cooper-Blacketer D, Marshall VJ, Irizarry M, Younkin L, Good MA, Bliss TV, Hyman BT, Younkin SG, Hsiao KK. Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice. Nat Neurosci. 1999;2:271–6.CrossRefPubMed

go back to reference Takahashi RH, Almeida CG, Kearney PF, Yu F, Lin MT, Milner TA, Gouras GK. Oligomerization of Alzheimer’s beta-amyloid within processes and synapses of cultured neurons and brain. J Neurosci. 2004;24:3592–9.CrossRefPubMed Takahashi RH, Almeida CG, Kearney PF, Yu F, Lin MT, Milner TA, Gouras GK. Oligomerization of Alzheimer’s beta-amyloid within processes and synapses of cultured neurons and brain. J Neurosci. 2004;24:3592–9.CrossRefPubMed

go back to reference Gouras GK, Tampellini D, Takahashi RH, Capetillo-Zarate E. Intraneuronal beta-amyloid accumulation and synapse pathology in Alzheimer’s disease. Acta Neuropathol. 2010;119:523–41.CrossRefPubMedPubMedCentral Gouras GK, Tampellini D, Takahashi RH, Capetillo-Zarate E. Intraneuronal beta-amyloid accumulation and synapse pathology in Alzheimer’s disease. Acta Neuropathol. 2010;119:523–41.CrossRefPubMedPubMedCentral

go back to reference Peric A, Annaert W. Early etiology of Alzheimer’s disease: tipping the balance toward autophagy or endosomal dysfunction? Acta Neuropathol. 2015;129:363–81.CrossRefPubMedPubMedCentral Peric A, Annaert W. Early etiology of Alzheimer’s disease: tipping the balance toward autophagy or endosomal dysfunction? Acta Neuropathol. 2015;129:363–81.CrossRefPubMedPubMedCentral

go back to reference Cataldo AM, Peterhoff CM, Troncoso JC, Gomez-Isla T, Hyman BT, Nixon RA. Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer’s disease and down syndrome: differential effects of APOE genotype and presenilin mutations. Am J Pathol. 2000;157:277–86.CrossRefPubMedPubMedCentral Cataldo AM, Peterhoff CM, Troncoso JC, Gomez-Isla T, Hyman BT, Nixon RA. Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer’s disease and down syndrome: differential effects of APOE genotype and presenilin mutations. Am J Pathol. 2000;157:277–86.CrossRefPubMedPubMedCentral

go back to reference Cataldo AM, Mathews PM, Boiteau AB, Hassinger LC, Peterhoff CM, Jiang Y, Mullaney K, Neve RL, Gruenberg J, Nixon RA. Down syndrome fibroblast model of Alzheimer-related endosome pathology: accelerated endocytosis promotes late endocytic defects. Am J Pathol. 2008;173:370–84.CrossRefPubMedPubMedCentral Cataldo AM, Mathews PM, Boiteau AB, Hassinger LC, Peterhoff CM, Jiang Y, Mullaney K, Neve RL, Gruenberg J, Nixon RA. Down syndrome fibroblast model of Alzheimer-related endosome pathology: accelerated endocytosis promotes late endocytic defects. Am J Pathol. 2008;173:370–84.CrossRefPubMedPubMedCentral

go back to reference Nixon RA, Wegiel J, Kumar A, Yu WH, Peterhoff C, Cataldo A, Cuervo AM. Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. J Neuropathol Exp Neurol. 2005;64:113–22.CrossRefPubMed Nixon RA, Wegiel J, Kumar A, Yu WH, Peterhoff C, Cataldo A, Cuervo AM. Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. J Neuropathol Exp Neurol. 2005;64:113–22.CrossRefPubMed

go back to reference Small SA, Gandy S. Sorting through the cell biology of Alzheimer’s disease: intracellular pathways to pathogenesis. Neuron. 2006;52:15–31.CrossRefPubMedPubMedCentral Small SA, Gandy S. Sorting through the cell biology of Alzheimer’s disease: intracellular pathways to pathogenesis. Neuron. 2006;52:15–31.CrossRefPubMedPubMedCentral

go back to reference De Strooper B, Vassar R, Golde T. The secretases: enzymes with therapeutic potential in Alzheimer disease. Nat Rev Neurol. 2010;6:99–107.CrossRefPubMedPubMedCentral De Strooper B, Vassar R, Golde T. The secretases: enzymes with therapeutic potential in Alzheimer disease. Nat Rev Neurol. 2010;6:99–107.CrossRefPubMedPubMedCentral

go back to reference Rajendran L, Annaert W. Membrane trafficking pathways in Alzheimer’s disease. Traffic. 2012;13:759–70.CrossRefPubMed Rajendran L, Annaert W. Membrane trafficking pathways in Alzheimer’s disease. Traffic. 2012;13:759–70.CrossRefPubMed

go back to reference Sannerud R, Declerck I, Peric A, Raemaekers T, Menendez G, Zhou L, Veerle B, Coen K, Munck S, De Strooper B, Schiavo G, Annaert W. ADP ribosylation factor 6 (ARF6) controls amyloid precursor protein (APP) processing by mediating the endosomal sorting of BACE1. Proc Natl Acad Sci U S A. 2011;108:E559–68.CrossRefPubMedPubMedCentral Sannerud R, Declerck I, Peric A, Raemaekers T, Menendez G, Zhou L, Veerle B, Coen K, Munck S, De Strooper B, Schiavo G, Annaert W. ADP ribosylation factor 6 (ARF6) controls amyloid precursor protein (APP) processing by mediating the endosomal sorting of BACE1. Proc Natl Acad Sci U S A. 2011;108:E559–68.CrossRefPubMedPubMedCentral

go back to reference Sannerud R, Esselens C, Ejsmont P, Mattera R, Rochin L, Tharkeshwar AK, De Baets G, De Wever V, Habets R, Baert V, Vermeire W, Michiels C, Groot AJ, Wouters R, Dillen K, Vints K, Baatsen P, Munck S, Derua R, Waelkens E, Basi GS, Mercken M, Vooijs M, Bollen M, Schymkowitz J, Rousseau F, Bonifacino JS, Van Niel G, De Strooper B, Annaert W. Restricted location of PSEN2/γ-Secretase determines substrate specificity and generates an intracellular Aβ pool. Cell. 2016;166:193–208.CrossRefPubMed Sannerud R, Esselens C, Ejsmont P, Mattera R, Rochin L, Tharkeshwar AK, De Baets G, De Wever V, Habets R, Baert V, Vermeire W, Michiels C, Groot AJ, Wouters R, Dillen K, Vints K, Baatsen P, Munck S, Derua R, Waelkens E, Basi GS, Mercken M, Vooijs M, Bollen M, Schymkowitz J, Rousseau F, Bonifacino JS, Van Niel G, De Strooper B, Annaert W. Restricted location of PSEN2/γ-Secretase determines substrate specificity and generates an intracellular Aβ pool. Cell. 2016;166:193–208.CrossRefPubMed

go back to reference Langui D, Girardot N, El Hachimi KH, Allinquant B, Blanchard V, Pradier L, Duyckaerts C. Subcellular topography of neuronal Abeta peptide in APPxPS1 transgenic mice. Am J Pathol. 2004;165:1465–77.CrossRefPubMedPubMedCentral Langui D, Girardot N, El Hachimi KH, Allinquant B, Blanchard V, Pradier L, Duyckaerts C. Subcellular topography of neuronal Abeta peptide in APPxPS1 transgenic mice. Am J Pathol. 2004;165:1465–77.CrossRefPubMedPubMedCentral

go back to reference Almeida C, Takahashi H, Gouras GK. Beta-amyloid accumulation impairs multivesicular body sorting by inhibiting the ubiquitin-proteasome system. J Neurosci. 2006;26:4277–88.CrossRefPubMed Almeida C, Takahashi H, Gouras GK. Beta-amyloid accumulation impairs multivesicular body sorting by inhibiting the ubiquitin-proteasome system. J Neurosci. 2006;26:4277–88.CrossRefPubMed

go back to reference Babst M, Katzmann DJ, Estepa-Sabal EJ, Meerloo T, Emr SD. Escrt-III: an endosome-associated heterooligomeric protein complex required for mvb sorting. Dev Cell. 2002;3:271–82.CrossRefPubMed Babst M, Katzmann DJ, Estepa-Sabal EJ, Meerloo T, Emr SD. Escrt-III: an endosome-associated heterooligomeric protein complex required for mvb sorting. Dev Cell. 2002;3:271–82.CrossRefPubMed

go back to reference Skibinski G, Parkinson NJ, Brown JM, Chakrabarti L, Lloyd SL, Hummerich H, Nielsen JE, Hodges JR, Spillantini MG, Thusgaard T, Brandner S, Brun A, Rossor MN, Gade A, Johannsen P, Sørensen SA, Gydesen S, Fisher EM, Collinge J. Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. Nat Genet. 2005;37:806–8.CrossRefPubMed Skibinski G, Parkinson NJ, Brown JM, Chakrabarti L, Lloyd SL, Hummerich H, Nielsen JE, Hodges JR, Spillantini MG, Thusgaard T, Brandner S, Brun A, Rossor MN, Gade A, Johannsen P, Sørensen SA, Gydesen S, Fisher EM, Collinge J. Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. Nat Genet. 2005;37:806–8.CrossRefPubMed

go back to reference Hooli BV, Kovacs-Vajna ZM, Mullin K, Blumenthal MA, Mattheisen M, Zhang C, Lange C, Mohapatra G, Bertram L, Tanzi RE. Rare autosomal copy number variations in early-onset familial Alzheimer’s disease. Mol Psychiatry. 2014;19:676–81.CrossRefPubMed Hooli BV, Kovacs-Vajna ZM, Mullin K, Blumenthal MA, Mattheisen M, Zhang C, Lange C, Mohapatra G, Bertram L, Tanzi RE. Rare autosomal copy number variations in early-onset familial Alzheimer’s disease. Mol Psychiatry. 2014;19:676–81.CrossRefPubMed

go back to reference Jones L, Holmans PA, Hamshere ML, Harold D, Moskvina V, Ivanov D, Pocklington A, Abraham R, Hollingworth P, Sims R, Gerrish A, Pahwa JS, Jones N, Stretton A, Morgan AR, Lovestone S, Powell J, Proitsi P, Lupton MK, Brayne C, Rubinsztein DC, Gill M, Lawlor B, Lynch A, Morgan K, Brown KS, Passmore PA, Craig D, McGuinness B, Todd S, Holmes C, Mann D, Smith AD, Love S, Kehoe PG, Mead S, Fox N, Rossor M, Collinge J, Maier W, Jessen F, Schürmann B, Heun R, Kölsch H, van den Bussche H, Heuser I, Peters O, Kornhuber J, Wiltfang J, Dichgans M, Frölich L, Hampel H, Hüll M, Rujescu D, Goate AM, Kauwe JS, Cruchaga C, Nowotny P, Morris JC, Mayo K, Livingston G, Bass NJ, Gurling H, McQuillin A, Gwilliam R, Deloukas P, Al-Chalabi A, Shaw CE, Singleton AB, Guerreiro R, Mühleisen TW, Nöthen MM, Moebus S, Jöckel KH, Klopp N, Wichmann HE, Rüther E, Carrasquillo MM, Pankratz VS, Younkin SG, Hardy J, O'Donovan MC, Owen MJ, Williams J. Genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer’s disease. PLoS One. 2010;5:e13950.CrossRefPubMedPubMedCentral Jones L, Holmans PA, Hamshere ML, Harold D, Moskvina V, Ivanov D, Pocklington A, Abraham R, Hollingworth P, Sims R, Gerrish A, Pahwa JS, Jones N, Stretton A, Morgan AR, Lovestone S, Powell J, Proitsi P, Lupton MK, Brayne C, Rubinsztein DC, Gill M, Lawlor B, Lynch A, Morgan K, Brown KS, Passmore PA, Craig D, McGuinness B, Todd S, Holmes C, Mann D, Smith AD, Love S, Kehoe PG, Mead S, Fox N, Rossor M, Collinge J, Maier W, Jessen F, Schürmann B, Heun R, Kölsch H, van den Bussche H, Heuser I, Peters O, Kornhuber J, Wiltfang J, Dichgans M, Frölich L, Hampel H, Hüll M, Rujescu D, Goate AM, Kauwe JS, Cruchaga C, Nowotny P, Morris JC, Mayo K, Livingston G, Bass NJ, Gurling H, McQuillin A, Gwilliam R, Deloukas P, Al-Chalabi A, Shaw CE, Singleton AB, Guerreiro R, Mühleisen TW, Nöthen MM, Moebus S, Jöckel KH, Klopp N, Wichmann HE, Rüther E, Carrasquillo MM, Pankratz VS, Younkin SG, Hardy J, O'Donovan MC, Owen MJ, Williams J. Genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer’s disease. PLoS One. 2010;5:e13950.CrossRefPubMedPubMedCentral

go back to reference Thinakaran G, Teplow DB, Siman R, Greenberg B, Sisodia SS. Metabolism of the “Swedish” amyloid precursor protein variant in neuro2a (N2a) cells. Evidence that cleavage at the “beta-secretase” site occurs in the golgi apparatus. J Biol Chem. 1996;271:9390–7.CrossRefPubMed Thinakaran G, Teplow DB, Siman R, Greenberg B, Sisodia SS. Metabolism of the “Swedish” amyloid precursor protein variant in neuro2a (N2a) cells. Evidence that cleavage at the “beta-secretase” site occurs in the golgi apparatus. J Biol Chem. 1996;271:9390–7.CrossRefPubMed

go back to reference Slot JW, Geuze HJ. A new method of preparing gold probes for multiple-labeling cytochemistry. Eur J Cell Biol. 1985;38:87–93.PubMed Slot JW, Geuze HJ. A new method of preparing gold probes for multiple-labeling cytochemistry. Eur J Cell Biol. 1985;38:87–93.PubMed

go back to reference Hasegawa T, Konno M, Baba T, Sugeno N, Kikuchi A, Kobayashi M, Miura E, Tanaka N, Tamai K, Furukawa K, Arai H, Mori F, Wakabayashi K, Aoki M, Itoyama Y, Takeda A. The AAA-ATPase VPS4 regulates extracellular secretion and lysosomal targeting of α-synuclein. PLoS One. 2011;6:e29460.CrossRefPubMedPubMedCentral Hasegawa T, Konno M, Baba T, Sugeno N, Kikuchi A, Kobayashi M, Miura E, Tanaka N, Tamai K, Furukawa K, Arai H, Mori F, Wakabayashi K, Aoki M, Itoyama Y, Takeda A. The AAA-ATPase VPS4 regulates extracellular secretion and lysosomal targeting of α-synuclein. PLoS One. 2011;6:e29460.CrossRefPubMedPubMedCentral

go back to reference Buxbaum JD, Gandy SE, Cicchetti P, Ehrlich ME, Czernik AJ, Fracasso RP, Ramabhadran TV, Unterbeck AJ, Greengard P. Processing of Alzheimer beta/A4 amyloid precursor protein: modulation by agents that regulate protein phosphorylation. Proc Natl Acad Sci U S A. 1990;87:6003–6.CrossRefPubMedPubMedCentral Buxbaum JD, Gandy SE, Cicchetti P, Ehrlich ME, Czernik AJ, Fracasso RP, Ramabhadran TV, Unterbeck AJ, Greengard P. Processing of Alzheimer beta/A4 amyloid precursor protein: modulation by agents that regulate protein phosphorylation. Proc Natl Acad Sci U S A. 1990;87:6003–6.CrossRefPubMedPubMedCentral

go back to reference Théry C, Amigorena S, Raposo G, Clayton A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol. 2006;30(3.22):3.22.1–3.22.29. Théry C, Amigorena S, Raposo G, Clayton A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol. 2006;30(3.22):3.22.1–3.22.29.

go back to reference Kayed R, Head E, Sarsoza F, Saing T, Cotman CW, Necula M, Margol L, Wu J, Breydo L, Thompson JL, Rasool S, Gurlo T, Butler P, Glabe CG. Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers. Mol Neurodegener. 2007;2:18.CrossRefPubMedPubMedCentral Kayed R, Head E, Sarsoza F, Saing T, Cotman CW, Necula M, Margol L, Wu J, Breydo L, Thompson JL, Rasool S, Gurlo T, Butler P, Glabe CG. Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers. Mol Neurodegener. 2007;2:18.CrossRefPubMedPubMedCentral

go back to reference Katoh Y, Ritter B, Gaffry T, Blondeau F, Höning S, McPherson PS. The clavesin family, neuron-specific lipid- and clathrin-binding sec14 proteins regulating lysosomal morphology. J Biol Chem. 2009;284:27646–54.CrossRefPubMedPubMedCentral Katoh Y, Ritter B, Gaffry T, Blondeau F, Höning S, McPherson PS. The clavesin family, neuron-specific lipid- and clathrin-binding sec14 proteins regulating lysosomal morphology. J Biol Chem. 2009;284:27646–54.CrossRefPubMedPubMedCentral

go back to reference Stuffers S, Sem Wegner C, Stenmark H, Brech A. Multivesicular endosome biogenesis in the absence of ESCRTs. Traffic. 2009;10:925–37.CrossRefPubMed Stuffers S, Sem Wegner C, Stenmark H, Brech A. Multivesicular endosome biogenesis in the absence of ESCRTs. Traffic. 2009;10:925–37.CrossRefPubMed

go back to reference van Niel G, Charrin S, Simoes S, Romao M, Rochin L, Saftig P, Marks MS, Rubinstein E, Raposo G. The tetraspanin CD63 regulates ESCRT-independent and -dependent endosomal sorting during melanogenesis. Dev Cell. 2011;21:708–21.CrossRefPubMedPubMedCentral van Niel G, Charrin S, Simoes S, Romao M, Rochin L, Saftig P, Marks MS, Rubinstein E, Raposo G. The tetraspanin CD63 regulates ESCRT-independent and -dependent endosomal sorting during melanogenesis. Dev Cell. 2011;21:708–21.CrossRefPubMedPubMedCentral

go back to reference Edgar JR, Eden ER, Futter CE. Hrs- and CD63-dependent competing mechanisms make different sized endosomal intraluminal vesicles. Traffic. 2014;15:197–211.CrossRefPubMedPubMedCentral Edgar JR, Eden ER, Futter CE. Hrs- and CD63-dependent competing mechanisms make different sized endosomal intraluminal vesicles. Traffic. 2014;15:197–211.CrossRefPubMedPubMedCentral

go back to reference Taelman VF, Dobrowolski R, Plouhinec JL, Fuentealba LC, Vorwald PP, Gumper I, Sabatini DD, De Robertis EM. Wnt signaling requires sequestration of glycogen synthase kinase 3 inside multivesicular endosomes. Cell. 2010;143:1136–48.CrossRefPubMedPubMedCentral Taelman VF, Dobrowolski R, Plouhinec JL, Fuentealba LC, Vorwald PP, Gumper I, Sabatini DD, De Robertis EM. Wnt signaling requires sequestration of glycogen synthase kinase 3 inside multivesicular endosomes. Cell. 2010;143:1136–48.CrossRefPubMedPubMedCentral

go back to reference Kimura T, Whitcomb DJ, Jo J, Regan P, Piers T, Heo S, Brown C, Hashikawa T, Murayama M, Seok H, Sotiropoulos I, Kim E, Collingridge GL, Takashima A, Cho K. Microtubule-associated protein tau is essential for long-term depression in the hippocampus. Philos Trans R Soc Lond Ser B Biol Sci. 2013;369:20130144.CrossRef Kimura T, Whitcomb DJ, Jo J, Regan P, Piers T, Heo S, Brown C, Hashikawa T, Murayama M, Seok H, Sotiropoulos I, Kim E, Collingridge GL, Takashima A, Cho K. Microtubule-associated protein tau is essential for long-term depression in the hippocampus. Philos Trans R Soc Lond Ser B Biol Sci. 2013;369:20130144.CrossRef

go back to reference Hooper C, Killick R, Lovestone S. The GSK3 hypothesis of Alzheimer’s disease. J Neurochem. 2008;104:1433–9.CrossRefPubMedPubMedCentral Hooper C, Killick R, Lovestone S. The GSK3 hypothesis of Alzheimer’s disease. J Neurochem. 2008;104:1433–9.CrossRefPubMedPubMedCentral

go back to reference Dunning CJ, McGauran G, Willén K, Gouras GK, O'Connell DJ, Linse S. Direct high affinity interaction between Aβ42 and GSK3α stimulates hyperphosphorylation of tau. A new molecular link in Alzheimer’s disease? ACS Chem Neurosci. 2016;7:161–70.CrossRefPubMed Dunning CJ, McGauran G, Willén K, Gouras GK, O'Connell DJ, Linse S. Direct high affinity interaction between Aβ42 and GSK3α stimulates hyperphosphorylation of tau. A new molecular link in Alzheimer’s disease? ACS Chem Neurosci. 2016;7:161–70.CrossRefPubMed

go back to reference Tampellini D, Rahman N, Lin MT, Capetillo-Zarate E, Gouras GK. Impaired beta-amyloid secretion in Alzheimer’s disease pathogenesis. J Neurosci. 2011;31:15384–90.CrossRefPubMedPubMedCentral Tampellini D, Rahman N, Lin MT, Capetillo-Zarate E, Gouras GK. Impaired beta-amyloid secretion in Alzheimer’s disease pathogenesis. J Neurosci. 2011;31:15384–90.CrossRefPubMedPubMedCentral

go back to reference Tampellini D, Capetillo-Zarate E, Dumont M, Huang Z, Yu F, Lin MT, Gouras GK. Effects of synaptic modulation on beta-amyloid, synaptophysin, and memory performance in Alzheimer’s disease transgenic mice. J Neurosci. 2010;30:14299–304.CrossRefPubMedPubMedCentral Tampellini D, Capetillo-Zarate E, Dumont M, Huang Z, Yu F, Lin MT, Gouras GK. Effects of synaptic modulation on beta-amyloid, synaptophysin, and memory performance in Alzheimer’s disease transgenic mice. J Neurosci. 2010;30:14299–304.CrossRefPubMedPubMedCentral

go back to reference Kim S, Sato Y, Mohan PS, Peterhoff C, Pensalfini A, Rigoglioso A, Jiang Y, Nixon RA. Evidence that the rab5 effector APPL1 mediates APP-βCTF-induced dysfunction of endosomes in down syndrome and Alzheimers disease. Mol Psychiatry. 2016;21:707–16.CrossRefPubMed Kim S, Sato Y, Mohan PS, Peterhoff C, Pensalfini A, Rigoglioso A, Jiang Y, Nixon RA. Evidence that the rab5 effector APPL1 mediates APP-βCTF-induced dysfunction of endosomes in down syndrome and Alzheimers disease. Mol Psychiatry. 2016;21:707–16.CrossRefPubMed

go back to reference Lauritzen I, Pardossi-Piquard R, Bourgeois A, Pagnotta S, Biferi MG, Barkats M, Lacor P, Klein W, Bauer C, Checler F. Intraneuronal aggregation of the β-CTF fragment of APP (C99) induces Aβ-independent lysosomal-autophagic pathology. Acta Neuropathol. 2016;132:257–76.CrossRefPubMedPubMedCentral Lauritzen I, Pardossi-Piquard R, Bourgeois A, Pagnotta S, Biferi MG, Barkats M, Lacor P, Klein W, Bauer C, Checler F. Intraneuronal aggregation of the β-CTF fragment of APP (C99) induces Aβ-independent lysosomal-autophagic pathology. Acta Neuropathol. 2016;132:257–76.CrossRefPubMedPubMedCentral

go back to reference Burdick D, Soreghan B, Kwon M, Kosmoski J, Knauer M, Henschen A, Yates J, Cotman C, Glabe C. Assembly and aggregation properties of synthetic Alzheimer’s A4/beta amyloid peptide analogs. J Biol Chem. 1992;267:546–54.PubMed Burdick D, Soreghan B, Kwon M, Kosmoski J, Knauer M, Henschen A, Yates J, Cotman C, Glabe C. Assembly and aggregation properties of synthetic Alzheimer’s A4/beta amyloid peptide analogs. J Biol Chem. 1992;267:546–54.PubMed

go back to reference Hu X, Crick SL, Bu G, Frieden C, Pappu RV, Lee JM. Amyloid seeds formed by cellular uptake, concentration, and aggregation of the amyloid-beta peptide. Proc Natl Acad Sci U S A. 2009;1(106):20324–9.CrossRef Hu X, Crick SL, Bu G, Frieden C, Pappu RV, Lee JM. Amyloid seeds formed by cellular uptake, concentration, and aggregation of the amyloid-beta peptide. Proc Natl Acad Sci U S A. 2009;1(106):20324–9.CrossRef

go back to reference Friedrich RP, Tepper K, Rönicke R, Soom M, Westermann M, Reymann K, Kaether C, Fändrich M. Mechanism of amyloid plaque formation suggests an intracellular basis of Aβ pathogenicity. Proc Natl Acad Sci U S A. 2010;107:1942–7.CrossRefPubMedPubMedCentral Friedrich RP, Tepper K, Rönicke R, Soom M, Westermann M, Reymann K, Kaether C, Fändrich M. Mechanism of amyloid plaque formation suggests an intracellular basis of Aβ pathogenicity. Proc Natl Acad Sci U S A. 2010;107:1942–7.CrossRefPubMedPubMedCentral

go back to reference Yang AJ, Chandswangbhuvana D, Margol L, Glabe CG. Loss of endosomal/lysosomal membrane impermeability is an early event in amyloid Abeta1-42 pathogenesis. J Neurosci Res. 1998;52:691–8.CrossRefPubMed Yang AJ, Chandswangbhuvana D, Margol L, Glabe CG. Loss of endosomal/lysosomal membrane impermeability is an early event in amyloid Abeta1-42 pathogenesis. J Neurosci Res. 1998;52:691–8.CrossRefPubMed

go back to reference Cataldo AM, Barnett JL, Mann DM, Nixon RA. Colocalization of lysosomal hydrolase and beta-amyloid in diffuse plaques of the cerebellum and striatum in Alzheimer's disease and Down’s syndrome. J Neuropathol Exp Neurol. 1996;55:704–15.CrossRefPubMed Cataldo AM, Barnett JL, Mann DM, Nixon RA. Colocalization of lysosomal hydrolase and beta-amyloid in diffuse plaques of the cerebellum and striatum in Alzheimer's disease and Down’s syndrome. J Neuropathol Exp Neurol. 1996;55:704–15.CrossRefPubMed

go back to reference Babst M, Wendland B, Estepa EJ, Emr SD. The Vps4p AAA ATPase regulates membrane association of a Vps protein complex required for normal endosome function. EMBO J. 1998;11:2982–93.CrossRef Babst M, Wendland B, Estepa EJ, Emr SD. The Vps4p AAA ATPase regulates membrane association of a Vps protein complex required for normal endosome function. EMBO J. 1998;11:2982–93.CrossRef

go back to reference Bishop N, Woodman P. ATPase-defective mammalian VPS4 localizes to aberrant endosomes and impairs cholesterol trafficking. Mol Biol Cell. 2000;11:227–39.CrossRefPubMedPubMedCentral Bishop N, Woodman P. ATPase-defective mammalian VPS4 localizes to aberrant endosomes and impairs cholesterol trafficking. Mol Biol Cell. 2000;11:227–39.CrossRefPubMedPubMedCentral

go back to reference Dores MR, Chen B, Lin H, Soh UJ, Paing MM, Montagne WA, Meerloo T, Trejo J. ALIX binds a YPX(3)L motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting. J Cell Biol. 2012;197:407–19.CrossRefPubMedPubMedCentral Dores MR, Chen B, Lin H, Soh UJ, Paing MM, Montagne WA, Meerloo T, Trejo J. ALIX binds a YPX(3)L motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting. J Cell Biol. 2012;197:407–19.CrossRefPubMedPubMedCentral

go back to reference Wollert T, Wunder C, Lippincott-Schwartz J, Hurley JH. Membrane scission by the ESCRT-III complex. Nature. 2009;458:172–7.CrossRefPubMedPubMedCentral Wollert T, Wunder C, Lippincott-Schwartz J, Hurley JH. Membrane scission by the ESCRT-III complex. Nature. 2009;458:172–7.CrossRefPubMedPubMedCentral

go back to reference Choy RW, Cheng Z, Schekman R. Amyloid precursor protein (APP) traffics from the cell surface via endosomes for amyloid β (Aβ) production in the trans-Golgi network. Proc Natl Acad Sci U S A. 2012;109:E2077–82.CrossRefPubMedPubMedCentral Choy RW, Cheng Z, Schekman R. Amyloid precursor protein (APP) traffics from the cell surface via endosomes for amyloid β (Aβ) production in the trans-Golgi network. Proc Natl Acad Sci U S A. 2012;109:E2077–82.CrossRefPubMedPubMedCentral

go back to reference Edgar JR, Willén K, Gouras GK, Futter CE. ESCRTs regulate amyloid precursor protein sorting in multivesicular bodies and intracellular amyloid-β accumulation. J Cell Sci. 2015;128:2520–8.CrossRefPubMedPubMedCentral Edgar JR, Willén K, Gouras GK, Futter CE. ESCRTs regulate amyloid precursor protein sorting in multivesicular bodies and intracellular amyloid-β accumulation. J Cell Sci. 2015;128:2520–8.CrossRefPubMedPubMedCentral

go back to reference Colombo M, Moita C, van Niel G, Kowal J, Vigneron J, Benaroch P, Manel N, Moita LF, Théry C, Raposo G. Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J Cell Sci. 2013;126:5553–65.CrossRefPubMed Colombo M, Moita C, van Niel G, Kowal J, Vigneron J, Benaroch P, Manel N, Moita LF, Théry C, Raposo G. Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J Cell Sci. 2013;126:5553–65.CrossRefPubMed

go back to reference Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D, Wieland F, Schwille P, Brügger B, Simons M. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science. 2008;319:1244–7.CrossRefPubMed Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D, Wieland F, Schwille P, Brügger B, Simons M. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science. 2008;319:1244–7.CrossRefPubMed

go back to reference Runz H, Rietdorf J, Tomic I, de Bernard M, Beyreuther K, Pepperkok R, Hartmann T. Inhibition of intracellular cholesterol transport alters presenilin localization and amyloid precursor protein processing in neuronal cells. J Neurosci. 2002;22:679–89. Runz H, Rietdorf J, Tomic I, de Bernard M, Beyreuther K, Pepperkok R, Hartmann T. Inhibition of intracellular cholesterol transport alters presenilin localization and amyloid precursor protein processing in neuronal cells. J Neurosci. 2002;22:679–89.

go back to reference Terwel D, Muyllaert D, Dewachter I, Borghgraef P, Croes S, Devijver H, Van Leuven F. Amyloid activates GSK-3beta to aggravate neuronal tauopathy in bigenic mice. Am J Pathol. 2008;172:786–98.CrossRefPubMedPubMedCentral Terwel D, Muyllaert D, Dewachter I, Borghgraef P, Croes S, Devijver H, Van Leuven F. Amyloid activates GSK-3beta to aggravate neuronal tauopathy in bigenic mice. Am J Pathol. 2008;172:786–98.CrossRefPubMedPubMedCentral

go back to reference Kim JM, Wu H, Green G, Winkler CA, Kopp JB, Miner JH, Unanue ER, Shaw AS. CD2-associated protein haploinsufficiency is linked to glomerular disease susceptibility. Science. 2003;300:1298–300.CrossRefPubMed Kim JM, Wu H, Green G, Winkler CA, Kopp JB, Miner JH, Unanue ER, Shaw AS. CD2-associated protein haploinsufficiency is linked to glomerular disease susceptibility. Science. 2003;300:1298–300.CrossRefPubMed

go back to reference Ubelmann F, Burrinha T, Salavessa L, Gomes R, Ferreira C, Moreno N, Guimas AC. Bin1 and CD2AP polarise the endocytic generation of beta-amyloid. EMBO Rep. 2017;18:102–22.CrossRefPubMed Ubelmann F, Burrinha T, Salavessa L, Gomes R, Ferreira C, Moreno N, Guimas AC. Bin1 and CD2AP polarise the endocytic generation of beta-amyloid. EMBO Rep. 2017;18:102–22.CrossRefPubMed

go back to reference Yamazaki Y, Takahashi T, Hiji M, Kurashige T, Izumi Y, Yamawaki T, Matsumoto M. Immunopositivity for ESCRT-III subunit CHMP2B in granulovacuolar degeneration of neurons in the Alzheimer’s disease hippocampus. Neurosci Lett. 2010;477:86–90.CrossRefPubMed Yamazaki Y, Takahashi T, Hiji M, Kurashige T, Izumi Y, Yamawaki T, Matsumoto M. Immunopositivity for ESCRT-III subunit CHMP2B in granulovacuolar degeneration of neurons in the Alzheimer’s disease hippocampus. Neurosci Lett. 2010;477:86–90.CrossRefPubMed

go back to reference Funk KE, Mrak RE, Kuret J. Granulovacuolar degeneration (GVD) bodies of Alzheimer’s disease (AD) resemble late-stage autophagic organelles. Neuropathol Appl Neurobiol. 2011;37:295–306.CrossRefPubMedPubMedCentral Funk KE, Mrak RE, Kuret J. Granulovacuolar degeneration (GVD) bodies of Alzheimer’s disease (AD) resemble late-stage autophagic organelles. Neuropathol Appl Neurobiol. 2011;37:295–306.CrossRefPubMedPubMedCentral

go back to reference Thal DR, Del Tredici K, Ludolph AC, Hoozemans JJ, Rozemuller AJ, Braak H, Knippschild U. Stages of granulovacuolar degeneration: their relation to Alzheimer’s disease and chronic stress response. Acta Neuropathol. 2011;122:577–89.CrossRefPubMed Thal DR, Del Tredici K, Ludolph AC, Hoozemans JJ, Rozemuller AJ, Braak H, Knippschild U. Stages of granulovacuolar degeneration: their relation to Alzheimer’s disease and chronic stress response. Acta Neuropathol. 2011;122:577–89.CrossRefPubMed