Genetic polymorphism of cathepsin D is strongly associated with the risk for developing sporadic Alzheimer's disease

Papassotiropoulos, Andreas; Bagli, Metin; Feder, Oliver; Jessen, Frank; Maier, Wolfgang; Rao, Marie Luise; Ludwig, Michael; Schwab, Sibylle G.; Heun, Reinhard

doi:10.1016/s0304-3940(99)00071-3

Cited by 73 publications

(74 citation statements)

References 19 publications

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“…The case-control studies looking at the association between the CTSD C4T polymorphism and AD have produced inconclusive results with two positive and four negative associations. [9][10][11][12][13][14] However, three case-control studies that reported a negative association in Caucasians did observe a nonsignificant increase in T allele frequency in AD cases compared to controls. [11][12][13] The fourth negative case-control study showed a nonsignificant increase in younger AD patients carrying the T allele.…”

Section: Discussionmentioning

confidence: 98%

“…A functional polymorphism (C4T, Ala4Val) within exon 2 of the CTSD gene increases the secretion of pro-CTSD from the cell 8 and has also been reported as a risk factor in AD, although this finding has been challenged. [9][10][11][12][13][14][15] A role for CTSD in apoptosis has also been established, 16,17 and its importance in brain development has recently been highlighted owing to its involvement in congenital ovine neuronal lipofuscinosis. 18 …”

Section: Introductionmentioning

confidence: 99%

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Cathepsin D exon 2 polymorphism associated with general intelligence in a healthy older population

et al. 2003

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General intelligence is a heritable trait that is a risk factor for both the onset of dementia and the rate of cognitive decline in community-dwelling older persons. Previous studies screening for quantitative trait loci (QTLs) that influence general intelligence in healthy individuals have identified four loci, two of which are located within the genes insulin-like growth factor 2 receptor (IGF2R) and the Msx1 homeobox. Here, we report the finding of another QTL associated with general intelligence that is located within exon 2 of the cathepsin D (CTSD) gene. A group of 767 healthy adults with a follow-up period of over 15 years have been analyzed for cross-sectional and longitudinal trends in cognitive change using the Heim intelligence test score (AH4-1). We observed a significant association (P ¼ 0.01) between a functional C4T (Ala4Val) transition within exon 2 of the CTSD gene that increases the secretion of pro-CTSD from the cell, and the AH4-1 score at initial testing on entry to the longitudinal study. Interestingly, CTSD is transported by IGF2R from the trans Golgi network to the lysosome.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Cathepsin D exon 2 polymorphism associated with general intelligence in a healthy older population

et al. 2003

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“…Cathepsin D protein level and activity are increased in aging brain, and the CSF of AD patients (Cataldo et al, 1995;Hoffman et al, 1998). It is reported that cathepsin D gene is associated with sporadic AD (Papassotiropoulos et al, 1999) (Figure 2). …”

Section: 23mentioning

confidence: 94%

Amyloid Hypothesis and Alzheimer's Disease

Sun¹,

Zhang²

2011

Advanced Understanding of Neurodegenerative Diseases

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“…Indivíduos que apresentam esta síndrome manifestam um envelhecimento precoce e a maioria apresenta DA confirmada entre os 40 e 50 anos de idade, a nível clínico e neurolôgico 4 . Este gene codifica a proteína precursora da β-amilóide (APP) que se deposita nas placas senis do cérebro dos indivíduos afetados [5][6][7][8][9][10] .…”

Section: Introductionunclassified

“…A análise da ligação genética permitiu a identificação da maioria dos genes envolvidos. Para além do gene codificante de APP anteriormente mencionado, genes codificantes das proteínas presenilina 1 (PSEN1), presenilina 2 (PSEN2), apolipoproteína E (apoE), α-2-macroglobulina (A2M) e catepsina D foram também identificados [5][6][7][8][9][10] Entretanto, outros genes têm sido estudados, tendo sido encontrada uma possível ligação com a DAIT para os genes codificantes da apolipoproteína CI (apoCI), da α-1-antiquimiotripsina, do receptor sigma tipo 1, da enzima conversora de angiotensina, da α-2-macroglobulina, da proteína relacionada ao receptor de LDL (LRP), da interleucina 1α e β, da paraxonase, do transportador de serotonina e do receptor de serotonina [17][18][19][20][21] .…”

Section: Introductionunclassified

Apolipoproteína E e Doença de Alzheimer

Prado

Cardoso

2013

RNC

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RESUMOContexto. A doença de Alzheimer (DA) é uma demência que afeta indivíduos tanto em idades avançadas como em idades precoces. Trata-se de uma doença resultante de perdas das funções neuronais cognitivas que envolve principalmente a memória. Objetivo. Neste artigo pretende-se fazer uma breve revisão bibliográfica sobre o papel da apolipoproteína E (apoE) como fator de risco genético para o desenvolvimento de DA. Método. Para tal foi realizada uma revisão sistemática da literatura existente sobre o tema, tendo sido revistos 72 artigos científicos entre 1972 e 2007. Foram efetuadas pesquisas nos motores de busca da PubMed, B-on, Google Acadêmico, Medline e Science Direct, utilizando os unitermos: "apolipoprotein E" e "Alzheimer's disease". Resultados. Como resultados desta pesquisa verificou-se existir influência da apoE na acumulação do péptido β-amilóide e consequentemente na patogénese da DA. Foi ainda possível relacionar a presença dos diversos alelos codificantes da apoE (com localização 19q13.2) e suas combinações com um melhor ou pior prognóstico para o desenvolvimento de DA, sendo o alelo ε4 o responsável pelo aumento do risco de desenvolvimento precoce de DA. Conclusão. No entanto, esta apolipoproteína não é em si suficiente para causar DA, mas promove o aumento do risco do indivíduo vir a desenvolver a doença.Unitermos. Apolipoproteína E, Doença de Alzheimer, Demência, Fatores de Risco, Alelos da APOE.Citação. Prado D, Cardoso IL. Apolipoproteína E e Doença de Alzheimer. ABSTRACTBackground. Alzheimer's disease (AD) is a dementia that occurs not only in elderly individuals but also at young ages. It is a disease caused by loss of neuronal functions that mainly involves cognitive memory. Objective. In this paper, we intend to present a brief review of the role of apolipoprotein E (apoE) as a genetic risk factor for the development of AD. Method. For that, a systematic literature review about this subject was performed, being red 72 scientific papers from 1972 to 2007. Searches were done in the websites PubMed, B-on, Academic Google, Medline and Science Direct, using the keywords: "apolipoprotein E" and "Alzheimer's disease". Results. As results of this search, it was confirmed the influence of apoE in the accumulation of the β-amyloid peptide and consequently in the pathogenesis of AD. It was also possible to relate the presence of the various alleles coding for apoE (with location 19q13.2) and its combinations with a better or worse prognosis for AD development, being ε4 allele the one responsible for an increased risk for early development of AD. Conclusion. However, this apolipoprotein alone is not sufficient to cause AD, but promotes an increased risk of AD development.

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Genetic polymorphism of cathepsin D is strongly associated with the risk for developing sporadic Alzheimer's disease

Cited by 73 publications

References 19 publications

Cathepsin D exon 2 polymorphism associated with general intelligence in a healthy older population

Cathepsin D exon 2 polymorphism associated with general intelligence in a healthy older population

Amyloid Hypothesis and Alzheimer's Disease

Apolipoproteína E e Doença de Alzheimer

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