Cathepsin D gene and the risk of Alzheimer's disease: a population-based study and meta-analysis

M Schuur; M A Ikram; J C van Swieten; A Isaacs; J M Vergeer-Drop; A Hofman; B A Oostra; M M B Breteler; C M van Duijn

doi:10.1016/j.neurobiolaging.2009.10.011

Cathepsin D gene and the risk of Alzheimer's disease: a population-based study and meta-analysis

M Schuur, M A Ikram, J C van Swieten, A Isaacs, J M Vergeer-Drop, A Hofman, B A Oostra, M M B Breteler, C M van Duijn^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Cathepsin D (CTSD) is a gene involved in amyloid precursor protein processing and is considered a candidate for Alzheimer's disease (AD). The aim of the current study was to examine if variation in CTSD increases the risk of AD. We performed a candidate-gene analysis in a population-based cohort study (N=7983), and estimated the effect of CTSD on the risk of AD. Additionally, a large meta-analysis was performed incorporating our data and previously published data. The T-allele of CTSD rs17571 was associated with an increased risk of AD (p-value 0.007) in the Rotterdam Study. This association was predominantly found in APOE ε4 noncarriers. A meta-analysis of previously published data showed a significantly increased risk of AD in carriers of the T-allele of rs17571 (OR 1.22, 95% CI 1.03-1.44), irrespective of APOE ε4 carrier status. This study adds to the evidence that CTSD increases the risk of AD, although the effect size is moderate.

Original language	English
Pages (from-to)	1607-14
Number of pages	8
Journal	Neurobiology of Aging
Volume	32
Issue number	9
DOIs	https://doi.org/10.1016/j.neurobiolaging.2009.10.011
Publication status	Published - Sept 2011
Externally published	Yes

Keywords

Aged
Aged, 80 and over
Alzheimer Disease/epidemiology
Case-Control Studies
Cathepsin D/genetics
Cohort Studies
Evidence-Based Medicine/trends
Female
Genetic Predisposition to Disease/epidemiology
Humans
Longitudinal Studies
Male
Polymorphism, Single Nucleotide/genetics
Risk Factors

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10.1016/j.neurobiolaging.2009.10.011

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title = "Cathepsin D gene and the risk of Alzheimer's disease: a population-based study and meta-analysis",

abstract = "Cathepsin D (CTSD) is a gene involved in amyloid precursor protein processing and is considered a candidate for Alzheimer's disease (AD). The aim of the current study was to examine if variation in CTSD increases the risk of AD. We performed a candidate-gene analysis in a population-based cohort study (N=7983), and estimated the effect of CTSD on the risk of AD. Additionally, a large meta-analysis was performed incorporating our data and previously published data. The T-allele of CTSD rs17571 was associated with an increased risk of AD (p-value 0.007) in the Rotterdam Study. This association was predominantly found in APOE ε4 noncarriers. A meta-analysis of previously published data showed a significantly increased risk of AD in carriers of the T-allele of rs17571 (OR 1.22, 95% CI 1.03-1.44), irrespective of APOE ε4 carrier status. This study adds to the evidence that CTSD increases the risk of AD, although the effect size is moderate.",

keywords = "Aged, Aged, 80 and over, Alzheimer Disease/epidemiology, Case-Control Studies, Cathepsin D/genetics, Cohort Studies, Evidence-Based Medicine/trends, Female, Genetic Predisposition to Disease/epidemiology, Humans, Longitudinal Studies, Male, Polymorphism, Single Nucleotide/genetics, Risk Factors",

author = "M Schuur and Ikram, {M A} and {van Swieten}, {J C} and A Isaacs and Vergeer-Drop, {J M} and A Hofman and Oostra, {B A} and Breteler, {M M B} and {van Duijn}, {C M}",

year = "2011",

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doi = "10.1016/j.neurobiolaging.2009.10.011",

language = "English",

volume = "32",

pages = "1607--14",

journal = "Neurobiology of Aging",

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T1 - Cathepsin D gene and the risk of Alzheimer's disease

T2 - a population-based study and meta-analysis

AU - Schuur, M

AU - Ikram, M A

AU - van Swieten, J C

AU - Isaacs, A

AU - Vergeer-Drop, J M

AU - Hofman, A

AU - Oostra, B A

AU - Breteler, M M B

AU - van Duijn, C M

PY - 2011/9

Y1 - 2011/9

N2 - Cathepsin D (CTSD) is a gene involved in amyloid precursor protein processing and is considered a candidate for Alzheimer's disease (AD). The aim of the current study was to examine if variation in CTSD increases the risk of AD. We performed a candidate-gene analysis in a population-based cohort study (N=7983), and estimated the effect of CTSD on the risk of AD. Additionally, a large meta-analysis was performed incorporating our data and previously published data. The T-allele of CTSD rs17571 was associated with an increased risk of AD (p-value 0.007) in the Rotterdam Study. This association was predominantly found in APOE ε4 noncarriers. A meta-analysis of previously published data showed a significantly increased risk of AD in carriers of the T-allele of rs17571 (OR 1.22, 95% CI 1.03-1.44), irrespective of APOE ε4 carrier status. This study adds to the evidence that CTSD increases the risk of AD, although the effect size is moderate.

AB - Cathepsin D (CTSD) is a gene involved in amyloid precursor protein processing and is considered a candidate for Alzheimer's disease (AD). The aim of the current study was to examine if variation in CTSD increases the risk of AD. We performed a candidate-gene analysis in a population-based cohort study (N=7983), and estimated the effect of CTSD on the risk of AD. Additionally, a large meta-analysis was performed incorporating our data and previously published data. The T-allele of CTSD rs17571 was associated with an increased risk of AD (p-value 0.007) in the Rotterdam Study. This association was predominantly found in APOE ε4 noncarriers. A meta-analysis of previously published data showed a significantly increased risk of AD in carriers of the T-allele of rs17571 (OR 1.22, 95% CI 1.03-1.44), irrespective of APOE ε4 carrier status. This study adds to the evidence that CTSD increases the risk of AD, although the effect size is moderate.

KW - Aged

KW - Aged, 80 and over

KW - Alzheimer Disease/epidemiology

KW - Case-Control Studies

KW - Cathepsin D/genetics

KW - Cohort Studies

KW - Evidence-Based Medicine/trends

KW - Female

KW - Genetic Predisposition to Disease/epidemiology

KW - Humans

KW - Longitudinal Studies

KW - Male

KW - Polymorphism, Single Nucleotide/genetics

KW - Risk Factors

U2 - 10.1016/j.neurobiolaging.2009.10.011

DO - 10.1016/j.neurobiolaging.2009.10.011

M3 - Article

C2 - 19926167

SN - 0197-4580

VL - 32

SP - 1607

EP - 1614

JO - Neurobiology of Aging

JF - Neurobiology of Aging

IS - 9

ER -

Cathepsin D gene and the risk of Alzheimer's disease: a population-based study and meta-analysis

Abstract

Keywords

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