{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T03:45:29Z","timestamp":1780717529405,"version":"3.54.1"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurodegeneration"],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>\u03b1-synuclein is a small soluble, cytosolic protein which associates with vesicular membranes. It is a component of intracellular Lewy bodies present in Parkinson's disease and a subset of Alzheimer's disease (AD). In addition, early studies identified a fragment of \u03b1-synuclein in the amyloid plaques of AD patients. Hypothesizing that \u03b1-synuclein might modify the AD pathogenic process, we crossed the Tg2576 strain of <jats:italic>APP<\/jats:italic> transgenic mice onto an \u03b1-synuclein knockout background to determine the effects of \u03b1-synuclein on A\u03b2 production and plaque deposition. We found that \u03b1-synuclein deficiency does not affect the A\u03b2 levels, nor does it alter the age of onset of plaque pathology. To our surprise, however, loss of \u03b1-synuclein leads to a significant increase in plaque load in all areas of the forebrain at 18 months of age. This is associated with an increase in another synaptic protein, synaptophysin. We thus conclude that \u03b1-synuclein is not involved in seeding of the plaques, but rather suppresses the progression of plaque pathology at advanced stages.<\/jats:p>","DOI":"10.1186\/1750-1326-2-6","type":"journal-article","created":{"date-parts":[[2007,5,2]],"date-time":"2007-05-02T15:36:18Z","timestamp":1178120178000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Lack of \u03b1-synuclein increases amyloid plaque accumulation in a transgenic mouse model of Alzheimer's disease"],"prefix":"10.1186","volume":"2","author":[{"given":"Verena","family":"Kallhoff","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Peethumnongsin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2007,3,16]]},"reference":[{"issue":"3 Suppl","key":"25_CR1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3233\/JAD-2006-9S305","volume":"9","author":"H Braak","year":"2006","unstructured":"Braak H, Rub U, Schultz C, Del Tredici K: Vulnerability of Cortical Neurons to Alzheimer's and Parkinson's Diseases. J Alzheimers Dis. 2006, 9 (3 Suppl): 35-44.","journal-title":"J Alzheimers Dis"},{"key":"25_CR2","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1146\/annurev.neuro.26.041002.131334","volume":"26","author":"D Selkoe","year":"2003","unstructured":"Selkoe D, Kopan R: Notch and Presenilin: Regulated Intramembrane Proteolysis Links Development and Degeneration. Annu Rev Neurosci. 2003, 26: 565-97. 10.1146\/annurev.neuro.26.041002.131334.","journal-title":"Annu Rev Neurosci"},{"issue":"3","key":"25_CR3","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/S0896-6273(03)00684-6","volume":"40","author":"JL Eriksen","year":"2003","unstructured":"Eriksen JL, Dawson TM, Dickson DW, Petrucelli L: Caught in the Act: Alpha-Synuclein Is the Culprit in Parkinson's Disease. Neuron. 2003, 40 (3): 453-6. 10.1016\/S0896-6273(03)00684-6.","journal-title":"Neuron"},{"issue":"6","key":"25_CR4","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1016\/S0896-6273(01)00439-1","volume":"31","author":"BI Giasson","year":"2001","unstructured":"Giasson BI, Lee VM: Parkin and the Molecular Pathways of Parkinson's Disease. Neuron. 2001, 31 (6): 885-8. 10.1016\/S0896-6273(01)00439-1.","journal-title":"Neuron"},{"issue":"23","key":"25_CR5","doi-asserted-by":"publisher","first-page":"11282","DOI":"10.1073\/pnas.90.23.11282","volume":"90","author":"K Ueda","year":"1993","unstructured":"Ueda K, Fukushima H, Masliah E, Xia Y, Iwai A, Yoshimoto M, Otero DA, Kondo J, Ihara Y, Saitoh T: Molecular Cloning of Cdna Encoding an Unrecognized Component of Amyloid in Alzheimer Disease. Proc Natl Acad Sci USA. 1993, 90 (23): 11282-6. 10.1073\/pnas.90.23.11282.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"2","key":"25_CR6","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/0896-6273(95)90302-X","volume":"14","author":"A Iwai","year":"1995","unstructured":"Iwai A, Masliah E, Yoshimoto M, Ge N, Flanagan L, de Silva HA, Kittel A, Saitoh T: The Precursor Protein of Non-a Beta Component of Alzheimer's Disease Amyloid Is a Presynaptic Protein of the Central Nervous System. Neuron. 1995, 14 (2): 467-75. 10.1016\/0896-6273(95)90302-X.","journal-title":"Neuron"},{"issue":"32","key":"25_CR7","doi-asserted-by":"publisher","first-page":"10139","DOI":"10.1021\/bi00032a006","volume":"34","author":"A Iwai","year":"1995","unstructured":"Iwai A, Yoshimoto M, Masliah E, Saitoh T: Non-a Beta Component of Alzheimer's Disease Amyloid (Nac) Is Amyloidogenic. Biochemistry. 1995, 34 (32): 10139-45. 10.1021\/bi00032a006.","journal-title":"Biochemistry"},{"issue":"9","key":"25_CR8","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1007\/s11064-006-9140-9","volume":"31","author":"PK Mandal","year":"2006","unstructured":"Mandal PK, Pettegrew JW, Masliah E, Hamilton RL, Mandal R: Interaction between Abeta Peptide and Alpha Synuclein: Molecular Mechanisms in Overlapping Pathology of Alzheimer's and Parkinson's in Dementia with Lewy Body Disease. Neurochem Res. 2006, 31 (9): 1153-62. 10.1007\/s11064-006-9140-9.","journal-title":"Neurochem Res"},{"issue":"2","key":"25_CR9","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/S0006-8993(99)02207-6","volume":"853","author":"F Yang","year":"2000","unstructured":"Yang F, Ueda K, Chen P, Ashe KH, Cole GM: Plaque-Associated Alpha-Synuclein (Nacp) Pathology in Aged Transgenic Mice Expressing Amyloid Precursor Protein. Brain Res. 2000, 853 (2): 381-3. 10.1016\/S0006-8993(99)02207-6.","journal-title":"Brain Res"},{"issue":"21","key":"25_CR10","doi-asserted-by":"publisher","first-page":"12245","DOI":"10.1073\/pnas.211412398","volume":"98","author":"E Masliah","year":"2001","unstructured":"Masliah E, Rockenstein E, Veinbergs I, Sagara Y, Mallory M, Hashimoto M, Mucke L: Beta-Amyloid Peptides Enhance Alpha-Synuclein Accumulation and Neuronal Deficits in a Transgenic Mouse Model Linking Alzheimer's Disease and Parkinson's Disease. Proc Natl Acad Sci USA. 2001, 98 (21): 12245-50. 10.1073\/pnas.211412398.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"4","key":"25_CR11","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1016\/S0002-9440(10)65220-0","volume":"155","author":"JG Culvenor","year":"1999","unstructured":"Culvenor JG, McLean CA, Cutt S, Campbell BC, Maher F, Jakala P, Hartmann T, Beyreuther K, Masters CL, Li QX: Non-Abeta Component of Alzheimer's Disease Amyloid (Nac) Revisited. Nac and Alpha-Synuclein Are Not Associated with Abeta Amyloid. Am J Pathol. 1999, 155 (4): 1173-81.","journal-title":"Am J Pathol"},{"issue":"3","key":"25_CR12","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1602\/neurorx.2.3.495","volume":"2","author":"SM Fleming","year":"2005","unstructured":"Fleming SM, Fernagut PO, Chesselet MF: Genetic Mouse Models of Parkinsonism: Strengths and Limitations. NeuroRx. 2005, 2 (3): 495-503. 10.1602\/neurorx.2.3.495.","journal-title":"NeuroRx"},{"issue":"1","key":"25_CR13","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/S0896-6273(00)80886-7","volume":"25","author":"A Abeliovich","year":"2000","unstructured":"Abeliovich A, Schmitz Y, Farinas I, Choi-Lundberg D, Ho WH, Castillo PE, Shinsky N, Verdugo JM, Armanini M, Ryan A, Hynes M, Phillips H, Sulzer D, Rosenthal A: Mice Lacking Alpha-Synuclein Display Functional Deficits in the Nigrostriatal Dopamine System. Neuron. 2000, 25 (1): 239-52. 10.1016\/S0896-6273(00)80886-7.","journal-title":"Neuron"},{"issue":"20","key":"25_CR14","doi-asserted-by":"crossref","first-page":"8797","DOI":"10.1523\/JNEUROSCI.22-20-08797.2002","volume":"22","author":"DE Cabin","year":"2002","unstructured":"Cabin DE, Shimazu K, Murphy D, Cole NB, Gottschalk W, McIlwain KL, Orrison B, Chen A, Ellis CE, Paylor R, Lu B, Nussbaum RL: Synaptic Vesicle Depletion Correlates with Attenuated Synaptic Responses to Prolonged Repetitive Stimulation in Mice Lacking Alpha-Synuclein. J Neurosci. 2002, 22 (20): 8797-807.","journal-title":"J Neurosci"},{"issue":"41","key":"25_CR15","doi-asserted-by":"publisher","first-page":"14966","DOI":"10.1073\/pnas.0406283101","volume":"101","author":"S Chandra","year":"2004","unstructured":"Chandra S, Fornai F, Kwon HB, Yazdani U, Atasoy D, Liu X, Hammer RE, Battaglia G, German DC, Castillo PE, Sudhof TC: Double-Knockout Mice for Alpha- and Beta-Synucleins: Effect on Synaptic Functions. Proc Natl Acad Sci USA. 2004, 101 (41): 14966-71. 10.1073\/pnas.0406283101.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"3","key":"25_CR16","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.cell.2005.09.028","volume":"123","author":"S Chandra","year":"2005","unstructured":"Chandra S, Gallardo G, Fernandez-Chacon R, Schluter OM, Sudhof TC: Alpha-Synuclein Cooperates with Cspalpha in Preventing Neurodegeneration. Cell. 2005, 123 (3): 383-96. 10.1016\/j.cell.2005.09.028.","journal-title":"Cell"},{"issue":"5284","key":"25_CR17","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1126\/science.274.5284.99","volume":"274","author":"K Hsiao","year":"1996","unstructured":"Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G: Correlative Memory Deficits, Abeta Elevation, and Amyloid Plaques in Transgenic Mice. Science. 1996, 274 (5284): 99-102. 10.1126\/science.274.5284.99.","journal-title":"Science"},{"issue":"30","key":"25_CR18","doi-asserted-by":"publisher","first-page":"6715","DOI":"10.1523\/JNEUROSCI.1594-04.2004","volume":"24","author":"DL Fortin","year":"2004","unstructured":"Fortin DL, Troyer MD, Nakamura K, Kubo S, Anthony MD, Edwards RH: Lipid Rafts Mediate the Synaptic Localization of Alpha-Synuclein. J Neurosci. 2004, 24 (30): 6715-23. 10.1523\/JNEUROSCI.1594-04.2004.","journal-title":"J Neurosci"},{"issue":"36","key":"25_CR19","doi-asserted-by":"publisher","first-page":"31664","DOI":"10.1074\/jbc.M504894200","volume":"280","author":"S Kubo","year":"2005","unstructured":"Kubo S, Nemani VM, Chalkley RJ, Anthony MD, Hattori N, Mizuno Y, Edwards RH, Fortin DL: A Combinatorial Code for the Interaction of Alpha-Synuclein with Membranes. J Biol Chem. 2005, 280 (36): 31664-72. 10.1074\/jbc.M504894200.","journal-title":"J Biol Chem"},{"issue":"26","key":"25_CR20","doi-asserted-by":"publisher","first-page":"7931","DOI":"10.1021\/bi060799c","volume":"45","author":"MS Wolfe","year":"2006","unstructured":"Wolfe MS: The Gamma-Secretase Complex: Membrane-Embedded Proteolytic Ensemble. Biochemistry. 2006, 45 (26): 7931-9. 10.1021\/bi060799c.","journal-title":"Biochemistry"},{"issue":"1","key":"25_CR21","first-page":"201","volume":"148","author":"E Masliah","year":"1996","unstructured":"Masliah E, Iwai A, Mallory M, Ueda K, Saitoh T: Altered Presynaptic Protein Nacp Is Associated with Plaque Formation and Neurodegeneration in Alzheimer's Disease. Am J Pathol. 1996, 148 (1): 201-10.","journal-title":"Am J Pathol"},{"key":"25_CR22","doi-asserted-by":"crossref","unstructured":"Gispert-Sanchez S, Auburger G: The Role of Protein Aggregates in Neuronal Pathology: Guilty, Innocent, or Just Trying to Help?. J Neural Transm Suppl. 2006, 111-7. 70","DOI":"10.1007\/978-3-211-45295-0_18"},{"issue":"2","key":"25_CR23","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1016\/S0002-9440(10)64777-3","volume":"156","author":"M Hashimoto","year":"2000","unstructured":"Hashimoto M, Takenouchi T, Mallory M, Masliah E, Takeda A: The Role of Nac in Amyloidogenesis in Alzheimer's Disease. Am J Pathol. 2000, 156 (2): 734-6.","journal-title":"Am J Pathol"},{"issue":"2","key":"25_CR24","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.expneurol.2005.10.018","volume":"199","author":"MC Quilty","year":"2006","unstructured":"Quilty MC, King AE, Gai WP, Pountney DL, West AK, Vickers JC, Dickson TC: Alpha-Synuclein Is Upregulated in Neurones in Response to Chronic Oxidative Stress and Is Associated with Neuroprotection. Exp Neurol. 2006, 199 (2): 249-56. 10.1016\/j.expneurol.2005.10.018.","journal-title":"Exp Neurol"},{"key":"25_CR25","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1196\/annals.1332.016","volume":"1035","author":"A Sidhu","year":"2004","unstructured":"Sidhu A, Wersinger C, Moussa CE, Vernier P: The Role of Alpha-Synuclein in Both Neuroprotection and Neurodegeneration. Ann N Y Acad Sci. 2004, 1035: 250-70. 10.1196\/annals.1332.016.","journal-title":"Ann N Y Acad Sci"},{"issue":"4","key":"25_CR26","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1097\/00001756-200303240-00004","volume":"14","author":"K Suzuki","year":"2003","unstructured":"Suzuki K, Iseki E, Katsuse O, Yamaguchi A, Katsuyama K, Aoki I, Yamanaka S, Kosaka K: Neuronal Accumulation of Alpha- and Beta-Synucleins in the Brain of a Gm2 Gangliosidosis Mouse Model. Neuroreport. 2003, 14 (4): 551-4. 10.1097\/00001756-200303240-00004.","journal-title":"Neuroreport"},{"issue":"22","key":"25_CR27","doi-asserted-by":"publisher","first-page":"15330","DOI":"10.1074\/jbc.M512574200","volume":"281","author":"R Wang","year":"2006","unstructured":"Wang R, Wang B, He W, Zheng H: Wild-Type Presenilin 1 Protects against Alzheimer Disease Mutation-Induced Amyloid Pathology. J Biol Chem. 2006, 281 (22): 15330-6. 10.1074\/jbc.M512574200.","journal-title":"J Biol Chem"}],"container-title":["Molecular Neurodegeneration"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1750-1326-2-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T03:02:33Z","timestamp":1630465353000},"score":1,"resource":{"primary":{"URL":"https:\/\/molecularneurodegeneration.biomedcentral.com\/articles\/10.1186\/1750-1326-2-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,3,16]]},"references-count":27,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2007,12]]}},"alternative-id":["25"],"URL":"https:\/\/doi.org\/10.1186\/1750-1326-2-6","relation":{},"ISSN":["1750-1326"],"issn-type":[{"value":"1750-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,3,16]]},"assertion":[{"value":"23 February 2007","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2007","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2007","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"6"}}