Journal Mobile Options
Table of Contents
Vol. 3, No. 1, 2013
Issue release date: January – December
Section title: Original Research Article
Open Access Gateway
Dement Geriatr Cogn Disord Extra 2013;3:161-167
(DOI:10.1159/000351419)

Lack of Genetic Associations of PPAR-γ and PGC-1α with Alzheimer's Disease and Parkinson's Disease with Dementia

Shibata N.a · Motoi Y.b, d · Tomiyama H.b, c · Ohnuma T.a · Kuerban B.a · Tomson K.a, e · Komatsu M.a · Shimazaki H.a · Hattori N.b, c · Arai H.a
Departments of aPsychiatry, bNeurology and cNeuroscience for Neurodegenerative Disorders, Juntendo University School of Medicine, and dDepartment of Diagnosis, Prevention and Treatment of Dementia, Graduate School of Juntendo University, Tokyo, Japan; eDoctoral School of Behavioural, Social and Health Sciences, University of Tartu, Tartu, Estonia
email Corresponding Author

Abstract

Background and Aims: Similar clinical and pathological features have been observed in Alzheimer's disease (AD) and Parkinson's disease with dementia (PDD). Both the peroxisome proliferator-activated receptor-γ (PPAR-γ) gene and the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) gene are candidates modifying the risk for both diseases. The aim of this study was to clarify whether common single nucleotide polymorphisms (SNPs) of the PPAR-γ gene and the PGC-1α gene affect the onset of AD and PDD genetically. Methods: Four exonic SNPs of both genes (rs1801282 and rs3856806 of the PPAR-γ gene, rs3736265 and rs8192678 of the PGC-1α gene) were genotyped in 171 AD patients, 136 age-matched controls and 53 PDD patients. Haplotype analysis and logistic regression analysis with apolipoprotein E (APO E) status were performed for AD. Results: There was no statistical difference between AD cases and controls for the 4 SNPs, nor was there any statistical difference between PDD cases and controls for the 4 SNPs. We could not find any synergetic associations between these SNPs, APO E4 and AD. Conclusions: The 4 SNPs studied here did not influence the risk for AD in a Japanese population. As the number of PDD cases was small, comprehensive genetic studies considering diabetes would be needed.

© 2013 S. Karger AG, Basel


  

Key Words


  • PPAR-γ
  • PGC-1α
  • Apolipoprotein E
  • Polymorphism
  • Alzheimer’s disease
  • Parkinson’s disease
  • Dementia


 Introduction

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative disorders, and the onsets of the diseases are known to be affected by genetic and environmental factors. Similar clinical and pathological features have been observed in AD and PD [1,2]. One of the most frequent nonmotor symptoms in PD patients is dementia. PD with dementia (PDD) is supposed to have a more similar pathophysiological background with AD than PD. While apolipoprotein E4 (APO E4) is recognized as a genetic risk factor for familial and sporadic AD, the association between APO E4 and PDD has not been fully elucidated [3].

The peroxisome proliferator-activated receptor-γ (PPAR-γ) is a ligand-activated transcriptional factor and influences the expression or activity of various genes, including glucose homeostasis, energy metabolism and inflammation [4]. PPAR-γ agonists have been reported to provide neuroprotective effects against neurodegenerative diseases, including AD and PD [5,6]. These effects were surmised to result from anti-inflammatory actions of PPAR-γ [4]. A recent study showed that PPAR-γ affects amyloidogenic pathways and reduces amyloid β-stimulated inflammatory responses in primary astrocytes [6]. In addition, PPAR-γ also reduces amyloid deposition by repressing β-site amyloid precursor protein-cleaving enzyme-1 (BACE1) promoter activity [7]. These pieces of evidence have suggested that PPAR-γ could be a candidate gene for AD. The abundance of PPAR-γ in basal ganglia supports the association between PD and PPAR-γ. PPAR-γ agonists also rescue dopaminergic neurons in the PD model by inhibition of microglial activation [8]. There is increasing evidence that antioxidant mechanisms by PPAR-γ are also important for PD pathogenesis [9,10].

The Pro12Ala polymorphism (rs1801282) of the PPAR-γ gene has been reported to reduce the transcriptional activity of PPAR-γ [11]. It has been shown to be functional and to play potential roles in the AD pathogenesis [11,12]. Although several genetic studies on the polymorphism and the risk for AD have been issued, the associations are in debate. There have been few genetic studies on the polymorphism of the gene and PD.

The peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a metabolic coactivator playing a critical role in the control of glucose, lipid and energy metabolism. PGC-1α also induces mitochondrial biogenesis and exerts neuroprotective effects against several neurodegenerative diseases [13]. A number of studies reported that PGC-1α expressions were decreased in the AD brain [14]. Upregulation of PGC-1α protects against neurotoxicity induced by amyloid β1-42 [15,16]. These pieces of evidence also suggest that PGC-1α plays an important role in the pathophysiology of AD. Many researches showed that there are links between PD and type 2 diabetes mellitus (T2DM) with insulin resistance [17,18]. Insulin resistance was considered to be associated with mitochondrial dysfunction [19]. Polymorphisms in the PGC-1α gene have been associated with an increased risk for T2DM [20]. It was also shown that overexpression of PGC-1α has the potential to protect against dopaminergic cell loss induced by the mitochondrial toxin rotenone [21]. Converging data implicated that PGC-1α plays a major role in the PD pathogenesis.

Only a few pilot studies investigated the genetic association between the PGC-1α gene and AD, and there are few reports on the PGC-1α polymorphisms and PD. In this study, we tested whether common single nucleotide polymorphisms (SNPs) of the PPAR-γ gene and the PGC-1α gene affect the onset of AD and PDD genetically.

 

 Materials and Methods

DNA was extracted from white blood cells using a standard method. Our sporadic Japanese AD cases were obtained from the Department of Psychiatry, Juntendo University Hospital, Tokyo, Japan, and the Department of Psychiatry, Juntendo Koshigaya Hospital, Saitama, Japan. All the AD cases were diagnosed according to the NINCDS-ADRDA criteria and none had a familial history of AD. Japanese PDD cases were recruited from the Department of Neurology, Juntendo University Hospital. All the PDD cases were diagnosed using the UK PD Society Brain Bank clinical diagnostic criteria, and the scores of the Mini-Mental State Examination were under 24. The control cases were healthy volunteers with no history of dementia or other neuropsychiatric diseases.

The mean age of the AD group [n = 171 (male = 82, female = 89), age (mean ± SD) = 66.1 ± 10.1 years] was not significantly different from that of the control group [n = 136 (male = 63, female = 73), age = 63.8 ± 6.7 years]. However, the mean age of the PDD group [n = 53 (male = 32, female = 21), age = 60.4 ± 12.5 years] was significantly lower than that of the control group. The purpose and significance of this study were explained in detail to each patient and his/her family, and all subjects provided informed consent. The study protocols were approved by the Ethics Committee of the Juntendo University School of Medicine.

Information on the SNPs was obtained from the SNP database established by the National Center for Biotechnology Information. Two SNPs each of the PGC-1α gene and the PPAR-γ gene were genotyped using TaqMan technology on an ABI7500 system (Applied Biosystems, Carlsbad, Calif., USA). All probes and primers were designed by the Assay-by-Design service of Applied Biosystems. A standard PCR was carried out using the TaqMan Universal PCR Master Mix reagent kit in a 10-μl volume. Hardy-Weinberg equilibrium tests were performed for all SNPs. APO E genotypes for all the samples were determined according to a previous report [22]. Differences in the genotypic frequencies were evaluated using a case-control study design and applying Fisher's exact probabilities test.

Linkage disequilibrium (LD) between the SNPs as well as a haplotype analysis were performed using SNPAlyse version 5.1 (Dynacom, Yokohama, Japan). LD, denoted as D', was calculated from the haplotype frequency using the expectation-maximization algorithm. SNPs were considered to be in LD if D' was greater than 0.75. The individual haplotypes were tested for association by grouping all others together and applying the 2 tests with 1 degree of freedom. p values were calculated on the basis of 10,000 replications, and all p values reported are two-tailed. A logistic regression analysis was performed to estimate the relationship between the 4 SNPs of the PPAR-γ gene and the PGC-1α gene, APO E status and AD onset using SPSS software version 17.0 for Windows (Chicago, Ill., USA). A p value of <0.05 was considered statistically significant.

 

 Results

The 4 SNPs of the PPAR-γ gene and the PGC-1α gene were found to be in Hardy-Weinberg equilibrium. LD examination showed strong LD between rs1801282 and rs3856806 on the PPAR-γ gene in our Japanese cases. We also found that both rs3736265 and rs8192678 of the PGC-1α gene were in the same LD. The genotypic frequencies of the 4 SNPs are shown in table 1. There was no statistical difference between AD cases and controls for the 4 SNPs, nor was there any statistical difference between PDD cases and controls for the 4 SNPs. The haplotype frequencies on the 2 genes of the AD group did not differ from those of the control group (tables 2, 3). The multiple regression analysis, which analyzed the simultaneous effect of APO E and the 4 SNPs on AD onset, only detected an association between APO E4 and the risk for AD (table 4).

TAB01
Table 1. Genotypic frequencies of the SNPs of the PPAR-γ and PGC-1α genes

TAB02
Table 2. Case-control haplotype analysis for the 2 PPAR-γ SNPs

TAB03
Table 3. Case-control haplotype analysis for the 2 PGC-1α SNPs

TAB04
Table 4. Multiple regression analysis for the effect of PPAR-γ and PGC-1α SNPs and APO E on AD

 

 Discussion


 Alzheimer's Disease

To date, this is the first study to clarify genetic associations between common exonic SNPs of the PPAR-γ and PGC-1α genes and AD in a Japanese population. We failed to show a genetic association between the 4 SNPs and the onset of the disease. The 2 SNPs on each gene studied here were in the same LD; haplotype analysis could not detect any positive findings. Recently, a genetic association between the PPAR-γ Pro12Ala polymorphism and AD was studied in several populations [23]. Two studies have shown that the polymorphism modifies the risk for late-onset AD [24,25]. Scacchi et al. [26] reported that positive associations were observed only in AD patients aged 80 years or older. Compared with this, our case-control data set consisted of younger patients. Many studies have shown that the Pro12Ala polymorphism affects the risk for T2DM. Moreover, it was observed that the cognitive decline of a demented population with DM is influenced by this polymorphism [27]. Helisalmi et al. [28] have shown that the genetic risk of AD was not directly associated significantly with the polymorphism. Although our negative results are partially due to the difference in age, we suppose that the Pro12Ala polymorphism does not have a direct impact on the onset of AD. We also showed genotype data of rs3856806, which is a silent mutation and is in the same LD as the Pro12Ala polymorphism. Our haplotype analysis could not detect a genetic association between the 2 mutations and AD. Although the results were in accordance with previous studies of a Caucasian population [28], further genetic studies including several ethnic groups are needed.

One genetic association study analyzing 8 SNPs and AD has been reported previously [29]. We confirmed that rs8192678 (Gly482Ser) and rs3736265 (Thr612Met) are not associated with the disease. For rs8192678, our results were consistent with the former report. Although rs3736265 has not been previously analyzed in AD cases, our LD analysis revealed that the SNP was in the same LD as rs8192678. This suggested that the 2 SNPs genotyped here did not have effects on the risk for AD.

 Parkinson's Disease

To date, this is the first study to clarify the genetic association between SNPs of the PPAR-γ gene and PDD. Despite the small number of PDD cases, we could not find any associations between the 2 SNPs of the PPAR-γ gene and PDD. Recent studies suggested that diabetes is associated with an increased risk of PD. A number of reports proposed that insulin resistance, the main cause for T2DM, is mediated through mitochondrial dysfunctions. Mitochondrial dysfunctions are also surmised to be a pathological feature of PD. While cognitive decline among T2DM patients is supposed to be associated with the Pro12Ala polymorphism, its modification seemed complicated [30]. The current cohort was too small to perform a multifactorial analysis taking into account the polymorphism, T2DM and PDD. However, these detailed researches would clarify the pathological significance of the polymorphism in PDD.

We found one pilot study that tested the relationship between SNPs on the PGC-1α gene and PD. Although the authors observed potential associations between some SNPs on the gene and the risk or age of onset of the disease, rs8192678 was not found to be associated [31]. They did not show any LD or haplotype analysis of the PGC-1α gene from their Caucasian samples. A meta-analysis has indicated that rs8192678 was associated with the risk for T2DM in an Asian population [20]. The size of the PGC-1α gene is approximately 150 kb and is not fully clarified for PDD. We showed that the 2 exonic SNPs did not affect the risk for PDD. Our study could not cover the entire gene region. As some pieces of evidence showed that the polymorphisms of the PGC-1α gene might affect PD [31], comprehensive genetic studies covering the PGC-1α gene should be performed for both PDD and PD without dementia.

 

 Acknowledgements

This study was partially supported by the High Technology Research Center Grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan and the Sportology Center, Juntendo University Graduate School of Medicine. We are grateful for the technical assistance of Ms. K. Yamamoto.

 

 Disclosure Statement

We have no potential conflicts.


References

  1. Farlow MR, Cummings J: A modern hypothesis: the distinct pathologies of dementia associated with Parkinson's disease versus Alzheimer's disease. Dement Geriatr Cogn Disord 2008;25:301-308.
  2. Jellinger KA: Neuropathological aspects of Alzheimer disease, Parkinson disease and frontotemporal dementia. Neurodegener Dis 2008;5:118-121.
  3. Shibata N, Motoi Y, Tomiyama H, Ohnuma T, Kuerban B, Tomson K, Komatsu M, Hattori N, Arai H: Lack of genetic association of the UCHL1 gene with Alzheimer's disease and Parkinson's disease with dementia. Dement Geriatr Cogn Disord 2012;33:250-254.
  4. Chen YC, Wu JS, Tsai HD, Huang CY, Chen JJ, Sun GY, Lin TN: Peroxisome proliferator-activated receptor gamma (PPAR-γ) and neurodegenerative disorders. Mol Neurobiol 2012;46:114-124.
  5. Schintu N, Frau L, Ibba M, Caboni P, Garau A, Carboni E, Carta AR: PPAR-γ-mediated neuroprotection in a chronic mouse model of Parkinson's disease. Eur J Neurosci 2009;29:954-963.
  6. Wang HM, Zhao YX, Zhang S, Liu GD, Kang WY, Tang HD, Ding JQ, Chen SD: PPAR-γ agonist curcumin reduces the amyloid-β-stimulated inflammatory responses in primary astrocytes. J Alzheimers Dis 2010;20:1189-1199.
  7. Sastre M, Dewachter I, Rossner S, Bogdanovic N, Rosen E, Borghgraef P, Evert BO, Dumitrescu-Ozimek L, Thal DR, Landreth G, Walter J, Klockgether T, van Leuven F, Heneka MT: Nonsteroidal anti-inflammatory drugs repress beta-secretase gene promoter activity by the activation of PPARgamma. Proc Natl Acad Sci USA 2006;103:443-448.
  8. Sadeghian M, Marinova-Mutafchieva L, Broom L, Davis JB, Virley D, Medhurst AD, Dexter DT: Full and partial peroxisome proliferation-activated receptor-γ agonists, but not δ agonist, rescue of dopaminergic neurons in the 6-OHDA parkinsonian model is associated with inhibition of microglial activation and MMP expression. J Neuroimmunol 2012;246:69-77.
  9. Carta AR, Pisanu A: Modulating microglia activity with PPAR-γ agonists: a promising therapy for Parkinson's disease? Neurotox Res 2013;23:112-123.
  10. Carta AR, Pisanu A, Carboni E: Do PPAR-γ agonists have a future in Parkinson's disease therapy? Parkinsons Dis 2011;2011:689181.
  11. d'Abramo C, Zingg JM, Pizzuti A, Argellati F, Pronzato MA, Ricciarelli R: In vitro effect of PPAR-gamma2 Pro12Ala polymorphism on the deposition of Alzheimer's amyloid-beta peptides. Brain Res 2007;1173:1-5.
  12. Sauder S, Kolsch H, Lutjohann D, Schulz A, von Bergmann K, Maier W, Heun R: Influence of peroxisome proliferator-activated receptor gamma gene polymorphism on 24S-hydroxycholesterol levels in Alzheimer's patients. J Neural Transm 2005;112:1381-1389.
  13. Rona-Voros K, Weydt P: The role of PGC-1α in the pathogenesis of neurodegenerative disorders. Curr Drug Targets 2010;11:1262-1269.
  14. Qin W, Haroutunian V, Katsel P, Cardozo CP, Ho L, Buxbaum JD, Pasinetti GM: PGC-1alpha expression decreases in the Alzheimer disease brain as a function of dementia. Arch Neurol 2009;66:352-361.
  15. Katsouri L, Parr C, Bogdanovic N, Willem M, Sastre M: PPARγ co-activator-1α (PGC-1α) reduces amyloid-β generation through a PPARγ-dependent mechanism. J Alzheimers Dis 2011;25:151-162.
  16. Zhu X, Chen C, Ye D, Guan D, Ye L, Jin J, Zhao H, Chen Y, Wang Z, Wang X, Xu Y: Diammonium glycyrrhizinate upregulates PGC-1α and protects against Aβ1-42-induced neurotoxicity. PLoS One 2012;7:e35823.
  17. Cereda E, Barichella M, Cassani E, Caccialanza R, Pezzoli G: Clinical features of Parkinson disease when onset of diabetes came first: a case-control study. Neurology 2012;78:1507-1511.
  18. Sun Y, Chang YH, Chen HF, Su YH, Su HF, Li CY: Risk of Parkinson disease onset in patients with diabetes: a 9-year population-based cohort study with age and sex stratifications. Diabetes Care 2012;35:1047-1049.
  19. Aviles-Olmos I, Limousin P, Lees A, Foltynie T: Parkinson's disease, insulin resistance and novel agents of neuroprotection. Brain 2013;136:374-384.
  20. Jing C, Xueyao H, Linong J: Meta-analysis of association studies between five candidate genes and type 2 diabetes in Chinese Han population. Endocrine 2012;42:307-320.
  21. Ciron C, Lengacher S, Dusonchet J, Aebischer P, Schneider BL: Sustained expression of PGC-1α in the rat nigrostriatal system selectively impairs dopaminergic function. Hum Mol Genet 2012;21:1861-1876.
  22. Wenham PR, Price WH, Blandell G: Apolipoprotein E genotyping by one-stage PCR. Lancet 1991;337:1158-1159.
  23. Hamilton G, Proitsi P, Jehu L, Morgan A, Williams J, O'Donovan MC, Owen MJ, Powell JF, Lovestone S: Candidate gene association study of insulin signaling genes and Alzheimer's disease: evidence for SOS2, PCK1, and PPARgamma as susceptibility loci. Am J Med Genet B Neuropsychiatr Genet 2007;144B:508-516.
  24. Koivisto AM, Helisalmi S, Pihlajamaki J, Hiltunen M, Koivisto K, Moilanen L, Kuusisto J, Helkala EL, Hanninen T, Kervinen K, Kesaniemi YA, Laakso M, Soininen H: Association analysis of peroxisome proliferator-activated receptor gamma polymorphisms and late onset Alzheimer's disease in the Finnish population. Dement Geriatr Cogn Disord 2006;22:449-453.
  25. Yao L, Li K, Zhang L, Yao S, Piao Z, Song L: Influence of the Pro12Ala polymorphism of PPAR-gamma on age at onset and sRAGE levels in Alzheimer's disease. Brain Res 2009;1291:133-139.
  26. Scacchi R, Pinto A, Gambina G, Rosano A, Corbo RM: The peroxisome proliferator-activated receptor gamma (PPAR-gamma2) Pro12Ala polymorphism is associated with higher risk for Alzheimer's disease in octogenarians. Brain Res 2007;1139:1-5.
  27. Johnson W, Harris SE, Starr JM, Whalley LJ, Deary IJ: PPARG Pro12Ala genotype and risk of cognitive decline in elders? Maybe with diabetes. Neurosci Lett 2008;434:50-55.
  28. Helisalmi S, Tarvainen T, Vepsalainen S, Koivisto AM, Hiltunen M, Soininen H: Lack of genetic association between PPARG gene polymorphisms and Finnish late-onset Alzheimer's disease. Neurosci Lett 2008;441:233-236.
  29. Helisalmi S, Vepsalainen S, Hiltunen M, Koivisto AM, Salminen A, Laakso M, Soininen H: Genetic study between SIRT1, PPARD, PGC-1alpha genes and Alzheimer's disease. J Neurol 2008;255:668-673.
  30. West NA, Haan MN, Morgenstern H: The PPAR-gamma Pro12Ala polymorphism and risk of cognitive impairment in a longitudinal study. Neurobiol Aging 2010;31:741-746.

    External Resources

  31. Clark J, Reddy S, Zheng K, Betensky RA, Simon DK: Association of PGC-1alpha polymorphisms with age of onset and risk of Parkinson's disease. BMC Med Genet 2011;12:69.

  

Author Contacts

Nobuto Shibata, MD, PhD
Department of Psychiatry
Juntendo University School of Medicine
2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan)
E-Mail nshibata@juntendo.ac.jp

  

Article Information

Published online: May 18, 2013
Number of Print Pages : 7
Number of Figures : 0, Number of Tables : 4, Number of References : 31

  

Publication Details

Dementia and Geriatric Cognitive Disorders Extra

Vol. 3, No. 1, Year 2013 (Cover Date: January - December)

Journal Editor: Chan-Palay V. (Boston, Mass.)
ISSN: 1664-5464 (Print), eISSN: 1664-5464 (Online)

For additional information: http://www.karger.com/DEE


Open Access License / Drug Dosage / Disclaimer

Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Background and Aims: Similar clinical and pathological features have been observed in Alzheimer's disease (AD) and Parkinson's disease with dementia (PDD). Both the peroxisome proliferator-activated receptor-γ (PPAR-γ) gene and the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) gene are candidates modifying the risk for both diseases. The aim of this study was to clarify whether common single nucleotide polymorphisms (SNPs) of the PPAR-γ gene and the PGC-1α gene affect the onset of AD and PDD genetically. Methods: Four exonic SNPs of both genes (rs1801282 and rs3856806 of the PPAR-γ gene, rs3736265 and rs8192678 of the PGC-1α gene) were genotyped in 171 AD patients, 136 age-matched controls and 53 PDD patients. Haplotype analysis and logistic regression analysis with apolipoprotein E (APO E) status were performed for AD. Results: There was no statistical difference between AD cases and controls for the 4 SNPs, nor was there any statistical difference between PDD cases and controls for the 4 SNPs. We could not find any synergetic associations between these SNPs, APO E4 and AD. Conclusions: The 4 SNPs studied here did not influence the risk for AD in a Japanese population. As the number of PDD cases was small, comprehensive genetic studies considering diabetes would be needed.

© 2013 S. Karger AG, Basel


  

Author Contacts

Nobuto Shibata, MD, PhD
Department of Psychiatry
Juntendo University School of Medicine
2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan)
E-Mail nshibata@juntendo.ac.jp

  

Article Information

Published online: May 18, 2013
Number of Print Pages : 7
Number of Figures : 0, Number of Tables : 4, Number of References : 31

  

Publication Details

Dementia and Geriatric Cognitive Disorders Extra

Vol. 3, No. 1, Year 2013 (Cover Date: January - December)

Journal Editor: Chan-Palay V. (Boston, Mass.)
ISSN: 1664-5464 (Print), eISSN: 1664-5464 (Online)

For additional information: http://www.karger.com/DEE


Article / Publication Details

First-Page Preview
Abstract of Original Research Article

Published online: 5/18/2013
Issue release date: January – December

Number of Print Pages: 7
Number of Figures: 0
Number of Tables: 4

ISSN: (Print)
eISSN: 1664-5464 (Online)

For additional information: http://www.karger.com/DEE


Open Access License / Drug Dosage

Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Farlow MR, Cummings J: A modern hypothesis: the distinct pathologies of dementia associated with Parkinson's disease versus Alzheimer's disease. Dement Geriatr Cogn Disord 2008;25:301-308.
  2. Jellinger KA: Neuropathological aspects of Alzheimer disease, Parkinson disease and frontotemporal dementia. Neurodegener Dis 2008;5:118-121.
  3. Shibata N, Motoi Y, Tomiyama H, Ohnuma T, Kuerban B, Tomson K, Komatsu M, Hattori N, Arai H: Lack of genetic association of the UCHL1 gene with Alzheimer's disease and Parkinson's disease with dementia. Dement Geriatr Cogn Disord 2012;33:250-254.
  4. Chen YC, Wu JS, Tsai HD, Huang CY, Chen JJ, Sun GY, Lin TN: Peroxisome proliferator-activated receptor gamma (PPAR-γ) and neurodegenerative disorders. Mol Neurobiol 2012;46:114-124.
  5. Schintu N, Frau L, Ibba M, Caboni P, Garau A, Carboni E, Carta AR: PPAR-γ-mediated neuroprotection in a chronic mouse model of Parkinson's disease. Eur J Neurosci 2009;29:954-963.
  6. Wang HM, Zhao YX, Zhang S, Liu GD, Kang WY, Tang HD, Ding JQ, Chen SD: PPAR-γ agonist curcumin reduces the amyloid-β-stimulated inflammatory responses in primary astrocytes. J Alzheimers Dis 2010;20:1189-1199.
  7. Sastre M, Dewachter I, Rossner S, Bogdanovic N, Rosen E, Borghgraef P, Evert BO, Dumitrescu-Ozimek L, Thal DR, Landreth G, Walter J, Klockgether T, van Leuven F, Heneka MT: Nonsteroidal anti-inflammatory drugs repress beta-secretase gene promoter activity by the activation of PPARgamma. Proc Natl Acad Sci USA 2006;103:443-448.
  8. Sadeghian M, Marinova-Mutafchieva L, Broom L, Davis JB, Virley D, Medhurst AD, Dexter DT: Full and partial peroxisome proliferation-activated receptor-γ agonists, but not δ agonist, rescue of dopaminergic neurons in the 6-OHDA parkinsonian model is associated with inhibition of microglial activation and MMP expression. J Neuroimmunol 2012;246:69-77.
  9. Carta AR, Pisanu A: Modulating microglia activity with PPAR-γ agonists: a promising therapy for Parkinson's disease? Neurotox Res 2013;23:112-123.
  10. Carta AR, Pisanu A, Carboni E: Do PPAR-γ agonists have a future in Parkinson's disease therapy? Parkinsons Dis 2011;2011:689181.
  11. d'Abramo C, Zingg JM, Pizzuti A, Argellati F, Pronzato MA, Ricciarelli R: In vitro effect of PPAR-gamma2 Pro12Ala polymorphism on the deposition of Alzheimer's amyloid-beta peptides. Brain Res 2007;1173:1-5.
  12. Sauder S, Kolsch H, Lutjohann D, Schulz A, von Bergmann K, Maier W, Heun R: Influence of peroxisome proliferator-activated receptor gamma gene polymorphism on 24S-hydroxycholesterol levels in Alzheimer's patients. J Neural Transm 2005;112:1381-1389.
  13. Rona-Voros K, Weydt P: The role of PGC-1α in the pathogenesis of neurodegenerative disorders. Curr Drug Targets 2010;11:1262-1269.
  14. Qin W, Haroutunian V, Katsel P, Cardozo CP, Ho L, Buxbaum JD, Pasinetti GM: PGC-1alpha expression decreases in the Alzheimer disease brain as a function of dementia. Arch Neurol 2009;66:352-361.
  15. Katsouri L, Parr C, Bogdanovic N, Willem M, Sastre M: PPARγ co-activator-1α (PGC-1α) reduces amyloid-β generation through a PPARγ-dependent mechanism. J Alzheimers Dis 2011;25:151-162.
  16. Zhu X, Chen C, Ye D, Guan D, Ye L, Jin J, Zhao H, Chen Y, Wang Z, Wang X, Xu Y: Diammonium glycyrrhizinate upregulates PGC-1α and protects against Aβ1-42-induced neurotoxicity. PLoS One 2012;7:e35823.
  17. Cereda E, Barichella M, Cassani E, Caccialanza R, Pezzoli G: Clinical features of Parkinson disease when onset of diabetes came first: a case-control study. Neurology 2012;78:1507-1511.
  18. Sun Y, Chang YH, Chen HF, Su YH, Su HF, Li CY: Risk of Parkinson disease onset in patients with diabetes: a 9-year population-based cohort study with age and sex stratifications. Diabetes Care 2012;35:1047-1049.
  19. Aviles-Olmos I, Limousin P, Lees A, Foltynie T: Parkinson's disease, insulin resistance and novel agents of neuroprotection. Brain 2013;136:374-384.
  20. Jing C, Xueyao H, Linong J: Meta-analysis of association studies between five candidate genes and type 2 diabetes in Chinese Han population. Endocrine 2012;42:307-320.
  21. Ciron C, Lengacher S, Dusonchet J, Aebischer P, Schneider BL: Sustained expression of PGC-1α in the rat nigrostriatal system selectively impairs dopaminergic function. Hum Mol Genet 2012;21:1861-1876.
  22. Wenham PR, Price WH, Blandell G: Apolipoprotein E genotyping by one-stage PCR. Lancet 1991;337:1158-1159.
  23. Hamilton G, Proitsi P, Jehu L, Morgan A, Williams J, O'Donovan MC, Owen MJ, Powell JF, Lovestone S: Candidate gene association study of insulin signaling genes and Alzheimer's disease: evidence for SOS2, PCK1, and PPARgamma as susceptibility loci. Am J Med Genet B Neuropsychiatr Genet 2007;144B:508-516.
  24. Koivisto AM, Helisalmi S, Pihlajamaki J, Hiltunen M, Koivisto K, Moilanen L, Kuusisto J, Helkala EL, Hanninen T, Kervinen K, Kesaniemi YA, Laakso M, Soininen H: Association analysis of peroxisome proliferator-activated receptor gamma polymorphisms and late onset Alzheimer's disease in the Finnish population. Dement Geriatr Cogn Disord 2006;22:449-453.
  25. Yao L, Li K, Zhang L, Yao S, Piao Z, Song L: Influence of the Pro12Ala polymorphism of PPAR-gamma on age at onset and sRAGE levels in Alzheimer's disease. Brain Res 2009;1291:133-139.
  26. Scacchi R, Pinto A, Gambina G, Rosano A, Corbo RM: The peroxisome proliferator-activated receptor gamma (PPAR-gamma2) Pro12Ala polymorphism is associated with higher risk for Alzheimer's disease in octogenarians. Brain Res 2007;1139:1-5.
  27. Johnson W, Harris SE, Starr JM, Whalley LJ, Deary IJ: PPARG Pro12Ala genotype and risk of cognitive decline in elders? Maybe with diabetes. Neurosci Lett 2008;434:50-55.
  28. Helisalmi S, Tarvainen T, Vepsalainen S, Koivisto AM, Hiltunen M, Soininen H: Lack of genetic association between PPARG gene polymorphisms and Finnish late-onset Alzheimer's disease. Neurosci Lett 2008;441:233-236.
  29. Helisalmi S, Vepsalainen S, Hiltunen M, Koivisto AM, Salminen A, Laakso M, Soininen H: Genetic study between SIRT1, PPARD, PGC-1alpha genes and Alzheimer's disease. J Neurol 2008;255:668-673.
  30. West NA, Haan MN, Morgenstern H: The PPAR-gamma Pro12Ala polymorphism and risk of cognitive impairment in a longitudinal study. Neurobiol Aging 2010;31:741-746.

    External Resources

  31. Clark J, Reddy S, Zheng K, Betensky RA, Simon DK: Association of PGC-1alpha polymorphisms with age of onset and risk of Parkinson's disease. BMC Med Genet 2011;12:69.