Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Neurology
Published in: BMC Neurology 1/2014

Open Access 01-12-2014 | Research article

Lack of association between cathepsin D C224T polymorphism and Alzheimer’s disease risk: an update meta-analysis

Authors: Cuiju Mo, Qiliu Peng, Jingzhe Sui, Jian Wang, Yan Deng, Li Xie, Taijie Li, Yu He, Xue Qin, Shan Li

Published in: BMC Neurology | Issue 1/2014

Login to get access

Abstract

Background

Cathepsin D C224T polymorphism has been reported to associate with AD susceptibility. But the results were inconsistent. This study aimed to assess the relationship between C224T polymorphism and AD risk.

Methods

The relevant studies were identified by searching PubMed, Embase, Web of Science, Google Scholar and Wan fang electronic databases updated on July 2013. The relationship between Cathepsin D C224T polymorphism and AD risk was evaluated by ORs and 95% CIs.

Results

A total of 25 case-control studies including 5,602 cases and 11,049 controls were included in the meta-analysis. There was no association between C224T polymorphism and AD risk with all the studies were pooled in the meta-analysis (CT vs. CC: OR = 1.125, 95% CI = 0.974-1.299, P = 0.109; CT + TT vs. CC: OR = 1.136, 95% CI = 0.978-1.320, P = 0.094). Furthermore, when stratified by ethnicity, age of onset and APOEϵ4 status, significant association did not found in all subgroups.

Conclusion

The present meta-analysis suggested that the Cathepsin D C224T polymorphism was not associated with AD susceptibility.
Appendix
Available only for authorised users
Literature
1.
Caracciolo B, Palmer K, Monastero R, Winblad B, Backman L, Fratiglioni L: Occurrence of cognitive impairment and dementia in the community: a 9-year-long prospective study. Neurology. 2008, 70 (19 Pt 2): 1778-1785.CrossRefPubMed
2.
Gao S, Hendrie HC, Hall KS, Hui S: The relationships between age, sex, and the incidence of dementia and Alzheimer disease: a meta-analysis. Arch Gen Psychiatry. 1998, 55 (9): 809-815. 10.1001/archpsyc.55.9.809.CrossRefPubMed
3.
Launer LJ, Andersen K, Dewey ME, Letenneur L, Ott A, Amaducci LA, Brayne C, Copeland JR, Dartigues JF, Kragh-Sorensen P, et al: Rates and risk factors for dementia and Alzheimer’s disease: results from EURODEM pooled analyses. EURODEM Incidence Research Group and Work Groups. European Studies of Dementia. Neurology. 1999, 52 (1): 78-84. 10.1212/WNL.52.1.78.CrossRefPubMed
4.
Campion D, Dumanchin C, Hannequin D, Dubois B, Belliard S, Puel M, Thomas-Anterion C, Michon A, Martin C, Charbonnier F, et al: Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum. Am J Hum Genet. 1999, 65 (3): 664-670. 10.1086/302553.CrossRefPubMedPubMedCentral
5.
Rocca WA, Hofman A, Brayne C, Breteler MM, Clarke M, Copeland JR, Dartigues JF, Engedal K, Hagnell O, Heeren TJ, et al: Frequency and distribution of Alzheimer’s disease in Europe: a collaborative study of 1980-1990 prevalence findings. The EURODEM-Prevalence Research Group. Ann Neurol. 1991, 30 (3): 381-390. 10.1002/ana.410300310.CrossRefPubMed
6.
Li Y, Grupe A, Rowland C, Nowotny P, Kauwe JS, Smemo S, Hinrichs A, Tacey K, Toombs TA, Kwok S, et al: DAPK1 variants are associated with Alzheimer’s disease and allele-specific expression. Hum Mol Genet. 2006, 15 (17): 2560-2568. 10.1093/hmg/ddl178.CrossRefPubMed
7.
Reitz C, Jun G, Naj A, Rajbhandary R, Vardarajan BN, Wang LS, Valladares O, Lin CF, Larson EB, Graff-Radford NR, et al: Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E 4, and the risk of late-onset Alzheimer disease in African Americans. JAMA. 2013, 309 (14): 1483-1492. 10.1001/jama.2013.2973.CrossRefPubMedPubMedCentral
8.
Coon KD, Myers AJ, Craig DW, Webster JA, Pearson JV, Lince DH, Zismann VL, Beach TG, Leung D, Bryden L, et al: A high-density whole-genome association study reveals that APOE is the major susceptibility gene for sporadic late-onset Alzheimer’s disease. J Clin Psychiatry. 2007, 68 (4): 613-618. 10.4088/JCP.v68n0419.CrossRefPubMed
9.
Carrasquillo MM, Belbin O, Hunter TA, Ma L, Bisceglio GD, Zou F, Crook JE, Pankratz VS, Sando SB, Aasly JO, et al: Replication of BIN1 association with Alzheimer’s disease and evaluation of genetic interactions. J Alzheimers Dis. 2011, 24 (4): 751-758.PubMedPubMedCentral
10.
Sadik G, Kaji H, Takeda K, Yamagata F, Kameoka Y, Hashimoto K, Miyanaga K, Shinoda T: In vitro processing of amyloid precursor protein by cathepsin D. Int J Biochem Cell Biol. 1999, 31 (11): 1327-1337. 10.1016/S1357-2725(99)00053-9.CrossRefPubMed
11.
Wischik CM, Novak M, Thogersen HC, Edwards PC, Runswick MJ, Jakes R, Walker JE, Milstein C, Roth M, Klug A: Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease. Proc Natl Acad Sci USA. 1988, 85 (12): 4506-4510. 10.1073/pnas.85.12.4506.CrossRefPubMedPubMedCentral
12.
Touitou I, Capony F, Brouillet JP, Rochefort H: Missense polymorphism (C/T224) in the human cathepsin D pro-fragment determined by polymerase chain reaction–single strand conformational polymorphism analysis and possible consequences in cancer cells. Eur J Cancer. 1994, 30A (3): 390-394.CrossRefPubMed
13.
Payton A, Holland F, Diggle P, Rabbitt P, Horan M, Davidson Y, Gibbons L, Worthington J, Ollier WE, Pendleton N: Cathepsin D exon 2 polymorphism associated with general intelligence in a healthy older population. Mol Psychiatry. 2003, 8 (1): 14-18. 10.1038/sj.mp.4001239.CrossRefPubMed
14.
Papassotiropoulos A, Bagli M, Feder O, Jessen F, Maier W, Rao ML, Ludwig M, Schwab SG, Heun R: Genetic polymorphism of cathepsin D is strongly associated with the risk for developing sporadic Alzheimer’s disease. Neurosci Lett. 1999, 262 (3): 171-174. 10.1016/S0304-3940(99)00071-3.CrossRefPubMed
15.
Papassotiropoulos A, Bagli M, Kurz A, Kornhuber J, Forstl H, Maier W, Pauls J, Lautenschlager N, Heun R: A genetic variation of cathepsin D is a major risk factor for Alzheimer’s disease. Ann Neurol. 2000, 47 (3): 399-403. 10.1002/1531-8249(200003)47:3<399::AID-ANA22>3.0.CO;2-5.CrossRefPubMed
16.
Beyer K, Lao JI, Latorre P, Ariza A: Age at onset: an essential variable for the definition of genetic risk factors for sporadic Alzheimer’s disease. Ann N Y Acad Sci. 2005, 1057: 260-278. 10.1196/annals.1322.021.CrossRefPubMed
17.
Mariani E, Seripa D, Ingegni T, Nocentini G, Mangialasche F, Ercolani S, Cherubini A, Metastasio A, Pilotto A, Senin U, et al: Interaction of CTSD and A2M polymorphisms in the risk for Alzheimer’s disease. J Neurol Sci. 2006, 247 (2): 187-191. 10.1016/j.jns.2006.05.043.CrossRefPubMed
18.
Schuur M, Ikram MA, van Swieten JC, Isaacs A, Vergeer-Drop JM, Hofman A, Oostra BA, Breteler MM, van Duijn CM: Cathepsin D gene and the risk of Alzheimer’s disease: a population-based study and meta-analysis. Neurobiol Aging. 2011, 32 (9): 1607-1614. 10.1016/j.neurobiolaging.2009.10.011.CrossRefPubMed
19.
Sun Y, Shi JJ, Zhang SZ, Tang MN, Han HY, Guo YB, Ma C, Liu XH, Li T: [The C224T polymorphism in the cathepsin D gene is not associated with sporadic Alzheimer’s disease in Chinese]. Yi Chuan. 2005, 27 (2): 190-194.PubMed
20.
Li XQ, Chen D, Zhang ZX, Qu QM, Zhang JW: Association between cathepsin D polymorphism and Alzheimer’s disease in a Chinese Han population. Dement Geriatr Cogn Disord. 2004, 18 (2): 115-119. 10.1159/000079189.CrossRefPubMed
21.
Jhoo JH, Park WY, Kim KW, Lee KH, Lee DY, Youn JC, Choo IH, Seo JS, Woo JI: Lack of association of cathepsin D genetic polymorphism with Alzheimer’s disease in Koreans. Arch Gerontol Geriatr. 2005, 41 (2): 121-127. 10.1016/j.archger.2004.12.003.CrossRefPubMed
22.
Matsui T, Morikawa Y, Tojo M, Okamura N, Maruyama M, Hirai H, Chiba H, Matsushita S, Higuchi S, Arai H, et al: Cathepsin D polymorphism not associated with Alzheimer’s disease in Japanese. Ann Neurol. 2001, 49 (4): 544-545.CrossRefPubMed
23.
McIlroy SP, Dynan KB, McGleenon BM, Lawson JT, Passmore AP: Cathepsin D gene exon 2 polymorphism and sporadic Alzheimer’s disease. Neurosci Lett. 1999, 273 (2): 140-141. 10.1016/S0304-3940(99)00635-7.CrossRefPubMed
24.
Bhojak TJ, DeKosky ST, Ganguli M, Kamboh MI: Genetic polymorphisms in the cathespin D and interleukin-6 genes and the risk of Alzheimer’s disease. Neurosci Lett. 2000, 288 (1): 21-24. 10.1016/S0304-3940(00)01185-X.CrossRefPubMed
25.
Menzer G, Muller-Thomsen T, Meins W, Alberici A, Binetti G, Hock C, Nitsch RM, Stoppe G, Reiss J, Finckh U: Non-replication of association between cathepsin D genotype and late onset Alzheimer disease. Am J Med Genet. 2001, 105 (2): 179-182. 10.1002/ajmg.1204.CrossRefPubMed
26.
Bertram L, Guenette S, Jones J, Keeney D, Mullin K, Crystal A, Basu S, Yhu S, Deng A, Rebeck GW, et al: No evidence for genetic association or linkage of the cathepsin D (CTSD) exon 2 polymorphism and Alzheimer disease. Ann Neurol. 2001, 49 (1): 114-116. 10.1002/1531-8249(200101)49:1<114::AID-ANA18>3.0.CO;2-M.CrossRefPubMed
27.
Emahazion T, Feuk L, Jobs M, Sawyer SL, Fredman D, St Clair D, Prince JA, Brookes AJ: SNP association studies in Alzheimer’s disease highlight problems for complex disease analysis. Trends Genet. 2001, 17 (7): 407-413. 10.1016/S0168-9525(01)02342-3.CrossRefPubMed
28.
Bagnoli S, Nacmias B, Tedde A, Guarnieri BM, Cellini E, Ciantelli M, Petruzzi C, Bartoli A, Ortenzi L, Serio A, et al: Cathepsin D polymorphism in Italian sporadic and familial Alzheimer’s disease. Neurosci Lett. 2002, 328 (3): 273-276. 10.1016/S0304-3940(02)00547-5.CrossRefPubMed
29.
Mateo I, Sanchez-Guerra M, Combarros O, Llorca J, Infante J, Gonzalez-Garcia J, del Molino JP, Berciano J: Lack of association between cathepsin D genetic polymorphism and Alzheimer disease in a Spanish sample. Am J Med Genet. 2002, 114 (1): 31-33. 10.1002/ajmg.1623.CrossRefPubMed
30.
Styczynska M, Religa D, Pfeffer A, Luczywek E, Wasiak B, Styczynski G, Peplonska B, Gabryelewicz T, Golebiowski M, Kobrys M, et al: Simultaneous analysis of five genetic risk factors in Polish patients with Alzheimer’s disease. Neurosci Lett. 2003, 344 (2): 99-102. 10.1016/S0304-3940(03)00438-5.CrossRefPubMed
31.
Ingegni T, Nocentini G, Mariani E, Spazzafumo L, Polidori MC, Cherubini A, Catani M, Cadini D, Senin U, Mecocci P: Cathepsin D polymorphism in Italian elderly subjects with sporadic late-onset Alzheimer’s disease. Dement Geriatr Cogn Disord. 2003, 16 (3): 151-155. 10.1159/000071003.CrossRefPubMed
32.
Blomqvist ME, Reynolds C, Katzov H, Feuk L, Andreasen N, Bogdanovic N, Blennow K, Brookes AJ, Prince JA: Towards compendia of negative genetic association studies: an example for Alzheimer disease. Hum Genet. 2006, 119 (1–2): 29-37.CrossRefPubMed
33.
Davidson Y, Gibbons L, Pritchard A, Hardicre J, Wren J, Tian J, Shi J, Stopford C, Julien C, Thompson J, et al: Genetic associations between cathepsin D exon 2 C–> T polymorphism and Alzheimer’s disease, and pathological correlations with genotype. J Neurol Neurosurg Psychiatry. 2006, 77 (4): 515-517. 10.1136/jnnp.2005.063917.CrossRefPubMedPubMedCentral
34.
Capurso C, Solfrizzi V, D’Introno A, Colacicco AM, Capurso SA, Bifaro L, Menga R, Santamato A, Seripa D, Pilotto A, et al: Short arm of chromosome 11 and sporadic Alzheimer’s disease: catalase and cathepsin D gene polymorphisms. Neurosci Lett. 2008, 432 (3): 237-242. 10.1016/j.neulet.2007.12.026.CrossRefPubMed
35.
Albayrak O, Tirniceriu A, Riemenschneider M, Kurz A, Scherag A, Egensperger R: The cathepsin D (224C/T) polymorphism confers an increased risk to develop Alzheimer’s disease in men. J Gerontol A Biol Sci Med Sci. 2010, 65 (3): 219-224.CrossRefPubMed
36.
Crawford FC, Freeman MJ, Schinka J, Abdullah LI, Richards D, Sevush S, Duara R, Mullan MJ: The genetic association between Cathepsin D and Alzheimer’s disease. Neurosci Lett. 2000, 289 (1): 61-65. 10.1016/S0304-3940(00)01260-X.CrossRefPubMed
37.
Bertram L, McQueen MB, Mullin K, Blacker D, Tanzi RE: Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat Genet. 2007, 39 (1): 17-23. 10.1038/ng1934.CrossRefPubMed
38.
Ntais C, Polycarpou A, Ioannidis JP: Meta-analysis of the association of the cathepsin D Ala224Val gene polymorphism with the risk of Alzheimer’s disease: a HuGE gene-disease association review. Am J Epidemiol. 2004, 159 (6): 527-536. 10.1093/aje/kwh069.CrossRefPubMed
39.
Papassotiropoulos A, Lewis HD, Bagli M, Jessen F, Ptok U, Schulte A, Shearman MS, Heun R: Cerebrospinal fluid levels of beta-amyloid(42) in patients with Alzheimer’s disease are related to the exon 2 polymorphism of the cathepsin D gene. Neuroreport. 2002, 13 (10): 1291-1294. 10.1097/00001756-200207190-00015.CrossRefPubMed
40.
Corder EH, Huang R, Cathcart HM, Lanham IS, Parker GR, Cheng D, Smith S, Poduslo SE: Membership in genetic groups predicts Alzheimer disease. Rejuvenation Res. 2006, 9 (1): 89-93. 10.1089/rej.2006.9.89.CrossRefPubMed
41.
Papassotiropoulos A, Bagli M, Jessen F, Maier W, Forstl H, Kurz A, Heun R: Interaction of two genes possibly involved in the regulation of the amyloid precursor protein (APP) processing. Mol Psychiatry. 2000, 5 (3): 240-241. 10.1038/sj.mp.4000699.CrossRefPubMed
42.
Kolsch H, Ptok U, Majores M, Schmitz S, Rao ML, Maier W, Heun R: Putative association of polymorphism in the mannose 6-phosphate receptor gene with major depression and Alzheimer’s disease. Psychiatr Genet. 2004, 14 (2): 97-100. 10.1097/01.ypg.0000129204.58574.c2.CrossRefPubMed
43.
Capurso C, Solfrizzi V, D’Introno A, Colacicco AM, Capurso SA, Mastroianni F, Liaci M, Vendemiale G, Capurso A, Panza F: The cathepsin D gene exon 2 (C224T) polymorphism and sporadic Alzheimer’s disease in European populations. J Gerontol A Biol Sci Med Sci. 2005, 60 (8): 991-996. 10.1093/gerona/60.8.991.CrossRefPubMed
44.
Prince JA, Feuk L, Sawyer SL, Gottfries J, Ricksten A, Nagga K, Bogdanovic N, Blennow K, Brookes AJ: Lack of replication of association findings in complex disease: an analysis of 15 polymorphisms in prior candidate genes for sporadic Alzheimer’s disease. Eur J Hum Genet. 2001, 9 (6): 437-444. 10.1038/sj.ejhg.5200651.CrossRefPubMed
45.
Bernstein HG, Bruszis S, Schmidt D, Wiederanders B, Dorn A: Immunodetection of cathepsin D in neuritic plaques found in brains of patients with dementia of Alzheimer type. J Hirnforsch. 1989, 30 (5): 613-618.PubMed
46.
Cataldo AM, Barnett JL, Berman SA, Li J, Quarless S, Bursztajn S, Lippa C, Nixon RA: Gene expression and cellular content of cathepsin D in Alzheimer’s disease brain: evidence for early up-regulation of the endosomal-lysosomal system. Neuron. 1995, 14 (3): 671-680. 10.1016/0896-6273(95)90324-0.CrossRefPubMed
Metadata
Title
Lack of association between cathepsin D C224T polymorphism and Alzheimer’s disease risk: an update meta-analysis
Authors
Cuiju Mo
Qiliu Peng
Jingzhe Sui
Jian Wang
Yan Deng
Li Xie
Taijie Li
Yu He
Xue Qin
Shan Li
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2014
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/1471-2377-14-13

Other articles of this Issue 1/2014

BMC Neurology 1/2014 Go to the issue

Study protocol

Long-term sequelae of severe sepsis: cognitive impairment and structural brain alterations – an MRI study (LossCog MRI)

Research article

Clinical baseline factors predict response to natalizumab: their usefulness in patient selection

Case report

Multifocal hemosiderin depositions on T2*-weighted magnetic resonance imaging in a patient with pathology-proven systemic diffuse large B-cell lymphoma

Case report

Guillain-Barré syndrome presenting with Raynaud's phenomenon: a case report

Research article

Mindfulness-based interventions in multiple sclerosis: beneficial effects of Tai Chi on balance, coordination, fatigue and depression

Study protocol

Long term cerebral and vascular complications after irradiation of the neck in head and neck cancer patients: a prospective cohort study: study rationale and protocol