Plasma ATG5 is Increased in Alzheimer's Disease

Overview

Journal Sci Rep

Specialty Science

Date 2019 Mar 22

PMID 30894637

Citations 16

Authors

Sun-Jung Cho

Hyun Joung Lim

Chulman Jo

Moon Ho Park

Changsu Han

Young Ho Koh

Affiliations

Soon will be listed here.

Abstract

Alzheimer's disease (AD) is a major cause of dementia. Growing evidence suggests that dysregulation of autophagy, a cellular mechanism essential for self-digestion of damaged proteins and organelles, is involved in neurological degenerative diseases including AD. Previously, we reported that autophagosomes are increased in the brains of AD mouse model. However, the plasma levels of autophagic markers have not yet been investigated in patients with AD. In this study, we investigated the expression of autophagy-related genes 5 and 12 (ATG5 and ATG12, respectively) in cells in vitro upon amyloid-beta (Aβ) treatment and in the plasma of AD patients. ATG5-ATG12 complex levels were increased in primary rat cortical neurons and human umbilical vein endothelial cells after Aβ treatment. Furthermore, we compared plasma from 69 patients with dementia, 82 patients with mild cognitive impairment (MCI), and 127 cognitively normal control participants. Plasma levels of ATG5 were significantly elevated in patients with dementia (149.3 ± 7.5 ng/mL) or MCI (152.9 ± 6.9 ng/mL) compared with the control subjects (129.0 ± 4.1 ng/mL) (p = 0.034, p = 0.016, respectively). Our results indicate that alterations in the plasma ATG5 levels might be a potential biomarker in patients at risk for AD.

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References

Han C, Jo S, Kim N, Jo I, Park M . Study design and methods of the Ansan Geriatric Study (AGE study). BMC Neurol. 2009; 9:10. PMC: 2654857. DOI: 10.1186/1471-2377-9-10. View

Sahani M, Itakura E, Mizushima N . Expression of the autophagy substrate SQSTM1/p62 is restored during prolonged starvation depending on transcriptional upregulation and autophagy-derived amino acids. Autophagy. 2014; 10(3):431-41. PMC: 4077882. DOI: 10.4161/auto.27344. View

Xu J, Xia L, Shang Q, Du J, Zhu D, Wang Y . A Variant of the Autophagy-Related 5 Gene Is Associated with Child Cerebral Palsy. Front Cell Neurosci. 2018; 11:407. PMC: 5741640. DOI: 10.3389/fncel.2017.00407. View

Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R . Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature. 2006; 441(7095):885-9. DOI: 10.1038/nature04724. View

Li H, Qiu S, Li X, Li M, Peng Y . Autophagy biomarkers in CSF correlates with infarct size, clinical severity and neurological outcome in AIS patients. J Transl Med. 2015; 13:359. PMC: 4650838. DOI: 10.1186/s12967-015-0726-3. View

Pickford F, Masliah E, Britschgi M, Lucin K, Narasimhan R, Jaeger P . The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice. J Clin Invest. 2008; 118(6):2190-9. PMC: 2391284. DOI: 10.1172/JCI33585. View

Ravikumar B, Vacher C, Berger Z, Davies J, Luo S, Oroz L . Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet. 2004; 36(6):585-95. DOI: 10.1038/ng1362. View

McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan E . Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984; 34(7):939-44. DOI: 10.1212/wnl.34.7.939. View

Scheff S, Price D, Schmitt F, Mufson E . Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment. Neurobiol Aging. 2005; 27(10):1372-84. DOI: 10.1016/j.neurobiolaging.2005.09.012. View

10.

Wang C, Klionsky D . The molecular mechanism of autophagy. Mol Med. 2003; 9(3-4):65-76. PMC: 1430730. View

11.

Mizushima N, Yoshimori T, Ohsumi Y . Role of the Apg12 conjugation system in mammalian autophagy. Int J Biochem Cell Biol. 2003; 35(5):553-61. DOI: 10.1016/s1357-2725(02)00343-6. View

12.

Cho M, Cho K, Kang H, Jeon E, Kim H, Kwon H . Autophagy in microglia degrades extracellular β-amyloid fibrils and regulates the NLRP3 inflammasome. Autophagy. 2014; 10(10):1761-75. PMC: 4198361. DOI: 10.4161/auto.29647. View

13.

Crews L, Spencer B, Desplats P, Patrick C, Paulino A, Rockenstein E . Selective molecular alterations in the autophagy pathway in patients with Lewy body disease and in models of alpha-synucleinopathy. PLoS One. 2010; 5(2):e9313. PMC: 2824828. DOI: 10.1371/journal.pone.0009313. View

14.

Bahr B, Bendiske J . The neuropathogenic contributions of lysosomal dysfunction. J Neurochem. 2002; 83(3):481-9. DOI: 10.1046/j.1471-4159.2002.01192.x. View

15.

Nixon R, Wegiel J, Kumar A, Yu W, Peterhoff C, Cataldo A . Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. J Neuropathol Exp Neurol. 2005; 64(2):113-22. DOI: 10.1093/jnen/64.2.113. View

16.

Demircan G, Kaplan O, Ozdas S . Role of autophagy in the progress of coronary total occlusion. Bratisl Lek Listy. 2018; 119(2):103. DOI: 10.4149/BLL_2018_019. View

17.

Petersen R, Smith G, Waring S, Ivnik R, Tangalos E, Kokmen E . Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999; 56(3):303-8. DOI: 10.1001/archneur.56.3.303. View

18.

Jang B, Yun S, Ahn K, Song J, Jo S, Kim Y . Plasma carbonic anhydrase II protein is elevated in Alzheimer's disease. J Alzheimers Dis. 2010; 21(3):939-45. DOI: 10.3233/JAD-2010-100384. View

19.

Nixon R, Yang D . Autophagy failure in Alzheimer's disease--locating the primary defect. Neurobiol Dis. 2011; 43(1):38-45. PMC: 3096679. DOI: 10.1016/j.nbd.2011.01.021. View

20.

Skibinski G, Parkinson N, Brown J, Chakrabarti L, Lloyd S, Hummerich H . Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. Nat Genet. 2005; 37(8):806-8. DOI: 10.1038/ng1609. View