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01-08-2014 | Original Communication

The association between TOMM40 gene polymorphism and spontaneous brain activity in amnestic mild cognitive impairment

Authors: Xiaoyan Liu, Feng Bai, Chunxian Yue, Yongmei Shi, Hui Yu, Benyan Luo, Zhijun Zhang

Published in: Journal of Neurology | Issue 8/2014

Abstract

The outer mitochondria membrane 40 homolog (TOMM40) is thought to be involved in the mitochondrial function and to influence the susceptibility for the development of AD. To determine whether TOMM40 rs157581 polymorphism is a plausible modulator of spontaneous brain activity in amnestic mild cognitive impairment (aMCI) patients, 46 aMCI subjects and 21 healthy controls were recruited and explored. Each individual was firstly genotyped for TOMM40 rs157581 and was further assessed by resting-state functional MRI to evaluate regional brain activity using amplitude low-frequency fluctuation analysis (ALFF). aMCI patients showed decreased ALFF in the left inferior frontal gyrus and insula, and increased ALFF in right posterior cingulate, lingual gyrus and calcarine sulcus. A significant difference in the interaction of “groups × genotypes” was observed in the bilateral superior frontal gyrus, bilateral lingual gyrus, right calcarine sulcus and left cerebellum. These results demonstrated a pattern of change in ALFF values, in which increased and subsequently decreased ALFF values in parallel with the progression of aMCI symptoms. The present study shows for the first time that TOMM40 rs157581 polymorphism may modulate regional spontaneous brain activity and related to the progression of aMCI.

Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E (1999) Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 56:303–308CrossRefPubMed

Swerdlow RH, Khan SM (2004) A “mitochondrial cascade hypothesis” for sporadic Alzheimer’s disease. Med Hypotheses 63:8–20CrossRefPubMed

Swerdlow RH, Burns JM, Khan SM (2010) The Alzheimer’s disease mitochondrial cascade hypothesis. J Alzheimers Dis 20(Suppl 2):S265–S279PubMed

Caselli RJ, Dueck AC, Huentelman MJ, Lutz MW, Saunders AM, Reiman EM, Roses AD (2012) Longitudinal modeling of cognitive aging and the TOMM40 effect. Alzheimers Dement 8:490–495PubMedCentralCrossRefPubMed

Roses AD, Lutz MW, Crenshaw DG, Grossman I, Saunders AM, Gottschalk WK (2013) TOMM40 and APOE: requirements for replication studies of association with age of disease onset and enrichment of a clinical trial. Alzheimers Dement 9:132–136CrossRefPubMed

Grupe A, Abraham R, Li Y, Rowland C, Hollingworth P, Morgan A, Jehu L, Segurado R, Stone D, Schadt E, Karnoub M, Nowotny P, Tacey K, Catanese J, Sninsky J, Brayne C, Rubinsztein D, Gill M, Lawlor B, Lovestone S, Holmans P, O’Donovan M, Morris JC, Thal L, Goate A, Owen MJ, Williams J (2007) Evidence for novel susceptibility genes for late-onset Alzheimer’s disease from a genome-wide association study of putative functional variants. Hum Mol Genet 16:865–873CrossRefPubMed

Lyall DM, Royle NA, Harris SE, Bastin ME, Maniega SM, Murray C, Lutz MW, Saunders AM, Roses AD, del Valdes Hernandez MC, Starr JM, Porteous DJ, Wardlaw JM, Deary IJ (2013) Alzheimer’s disease susceptibility genes APOE and TOMM40, and hippocampal volumes in the Lothian birth cohort 1936. PLoS One 8:e80513PubMedCentralCrossRefPubMed

Johnson SC, La Rue A, Hermann BP, Xu G, Koscik RL, Jonaitis EM, Bendlin BB, Hogan KJ, Roses AD, Saunders AM, Lutz MW, Asthana S, Green RC, Sager MA (2011) The effect of TOMM40 poly-T length on gray matter volume and cognition in middle-aged persons with APOE epsilon3/epsilon3 genotype. Alzheimers Dement 7:456–465PubMedCentralCrossRefPubMed

Liu X, Yue C, Xu Z, Shu H, Pu M, Yu H, Shi Y, Zhuang L, Xu X, Zhang Z (2012) Association study of candidate gene polymorphisms with amnestic mild cognitive impairment in a Chinese population. PLoS One 7:e41198PubMedCentralCrossRefPubMed

10.

Fox MD, Raichle ME (2007) Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci 8:700–711CrossRefPubMed

11.

Chong MS, Sahadevan S (2005) Preclinical Alzheimer’s disease: diagnosis and prediction of progression. Lancet Neurol 4:576–579CrossRefPubMed

12.

Binnewijzend MA, Schoonheim MM, Sanz-Arigita E, Wink AM, van der Flier WM, Tolboom N, Adriaanse SM, Damoiseaux JS, Scheltens P, van Berckel BN, Barkhof F (2012) Resting-state fMRI changes in Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging 33:2018–2028CrossRefPubMed

13.

Biswal B, Yetkin FZ, Haughton VM, Hyde JS (1995) Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med 34:537–541CrossRefPubMed

14.

Xi Q, Zhao X, Wang P, Guo Q, Jiang H, Cao X, He Y, Yan C (2012) Spontaneous brain activity in mild cognitive impairment revealed by amplitude of low-frequency fluctuation analysis: a resting-state fMRI study. Radiol Med 117:865–871CrossRefPubMed

15.

Roussotte FF, Daianu M, Jahanshad N, Leonardo CD, Thompson PM (2013) Neuroimaging and genetic risk for Alzheimer’s disease and addiction-related degenerative brain disorders. Brain Imaging Behav 8:217–233

16.

Buckner RL, Andrews-Hanna JR, Schacter DL (2008) The brain’s default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci 1124:1–38CrossRefPubMed

17.

Herholz K, Salmon E, Perani D, Baron JC, Holthoff V, Frolich L, Schonknecht P, Ito K, Mielke R, Kalbe E, Zundorf G, Delbeuck X, Pelati O, Anchisi D, Fazio F, Kerrouche N, Desgranges B, Eustache F, Beuthien-Baumann B, Menzel C, Schroder J, Kato T, Arahata Y, Henze M, Heiss WD (2002) Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET. Neuroimage 17:302–316CrossRefPubMed

18.

Lustig C, Snyder AZ, Bhakta M, O’Brien KC, McAvoy M, Raichle ME, Morris JC, Buckner RL (2003) Functional deactivations: change with age and dementia of the Alzheimer type. Proc Natl Acad Sci USA 100:14504–14509PubMedCentralCrossRefPubMed

19.

Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, Bergstrom M, Savitcheva I, Huang GF, Estrada S, Ausen B, Debnath ML, Barletta J, Price JC, Sandell J, Lopresti BJ, Wall A, Koivisto P, Antoni G, Mathis CA, Langstrom B (2004) Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 55:306–319CrossRefPubMed

20.

Li G, Bekris LM, Leong L, Steinbart EJ, Shofer JB, Crane PK, Larson EB, Peskind ER, Bird TD, Yu CE (2013) TOMM40 intron 6 poly-T length, age at onset, and neuropathology of AD in individuals with APOE epsilon3/epsilon3. Alzheimers Dement 9:554–561PubMedCentralCrossRefPubMed

21.

Kim S, Swaminathan S, Shen L, Risacher SL, Nho K, Foroud T, Shaw LM, Trojanowski JQ, Potkin SG, Huentelman MJ, Craig DW, DeChairo BM, Aisen PS, Petersen RC, Weiner MW, Saykin AJ (2011) Genome-wide association study of CSF biomarkers Abeta1-42, t-tau, and p-tau181p in the ADNI cohort. Neurology 76:69–79PubMedCentralCrossRefPubMed

22.

Takei N, Miyashita A, Tsukie T, Arai H, Asada T, Imagawa M, Shoji M, Higuchi S, Urakami K, Kimura H, Kakita A, Takahashi H, Tsuji S, Kanazawa I, Ihara Y, Odani S, Kuwano R (2009) Genetic association study on in and around the APOE in late-onset Alzheimer disease in Japanese. Genomics 93:441–448CrossRefPubMed

23.

Yu CE, Seltman H, Peskind ER, Galloway N, Zhou PX, Rosenthal E, Wijsman EM, Tsuang DW, Devlin B, Schellenberg GD (2007) Comprehensive analysis of APOE and selected proximate markers for late-onset Alzheimer’s disease: patterns of linkage disequilibrium and disease/marker association. Genomics 89:655–665PubMedCentralCrossRefPubMed

24.

Shen L, Kim S, Risacher SL, Nho K, Swaminathan S, West JD, Foroud T, Pankratz N, Moore JH, Sloan CD, Huentelman MJ, Craig DW, Dechairo BM, Potkin SG, Jack CR Jr, Weiner MW, Saykin AJ (2010) Whole genome association study of brain-wide imaging phenotypes for identifying quantitative trait loci in MCI and AD: a study of the ADNI cohort. Neuroimage 53:1051–1063PubMedCentralCrossRefPubMed

25.

Potkin SG, Guffanti G, Lakatos A, Turner JA, Kruggel F, Fallon JH, Saykin AJ, Orro A, Lupoli S, Salvi E, Weiner M, Macciardi F (2009) Hippocampal atrophy as a quantitative trait in a genome-wide association study identifying novel susceptibility genes for Alzheimer’s disease. PLoS One 4:e6501PubMedCentralCrossRefPubMed

26.

Kar AN, Sun CY, Reichard K, Gervasi NM, Pickel J, Nakazawa K, Gioio AE, Kaplan BB (2014) Dysregulation of the axonal trafficking of nuclear-encoded mitochondrial mRNA alters neuronal mitochondrial activity and mouse behavior. Dev Neurobiol 74(3):333–350

27.

Kim KH, Moon M, Yu SB, Mook-Jung I, Kim JI (2012) RNA-Seq analysis of frontal cortex and cerebellum from 5XFAD mice at early stage of disease pathology. J Alzheimers Dis 29:793–808PubMed

28.

Kim SH, Vlkolinsky R, Cairns N, Fountoulakis M, Lubec G (2001) The reduction of NADH ubiquinone oxidoreductase 24- and 75-kDa subunits in brains of patients with Down syndrome and Alzheimer’s disease. Life Sci 68:2741–2750CrossRefPubMed

29.

Gauthier S, Reisberg B, Zaudig M, Petersen RC, Ritchie K, Broich K, Belleville S, Brodaty H, Bennett D, Chertkow H, Cummings JL, de Leon M, Feldman H, Ganguli M, Hampel H, Scheltens P, Tierney MC, Whitehouse P, Winblad B (2006) Mild cognitive impairment. Lancet 367:1262–1270CrossRefPubMed

Title: The association between TOMM40 gene polymorphism and spontaneous brain activity in amnestic mild cognitive impairment
Authors: Xiaoyan Liu
Feng Bai
Chunxian Yue
Yongmei Shi
Hui Yu
Benyan Luo
Zhijun Zhang
Publication date: 01-08-2014
Publisher: Springer Berlin Heidelberg
Published in: Journal of Neurology / Issue 8/2014
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-014-7368-x

At a glance: The STEP trials

Springer Medicine

The association between TOMM40 gene polymorphism and spontaneous brain activity in amnestic mild cognitive impairment

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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