ABCA1 modulates CSF cholesterol levels and influences the age at onset of Alzheimer's disease

Autor: M. Axel Wollmer, Thomas Hegi, Vassiliki Iakovidou, Dieter Lütjohann, Johannes Streffer, Roger M. Nitsch, Andreas Papassotiropoulos, Klaus von Bergmann, Magdalini Tsolaki, Hans H. Jung, Christoph Hock, Thomas Pasch
Přispěvatelé: University of Zurich, Wollmer, M A
Jazyk: angličtina
Rok vydání: 2003
Předmět:
Male
Aging
medicine.medical_specialty
Single-nucleotide polymorphism
Late onset
610 Medicine & health
2717 Geriatrics and Gerontology
Biology
1309 Developmental Biology
chemistry.chemical_compound
1302 Aging
Alzheimer Disease
Risk Factors
Internal medicine
medicine
ABCA1 Gene
Humans
Age of Onset
Allele
Aged
Amyloid beta-Peptides
Polymorphism
Genetic
Greece
Cholesterol
General Neuroscience
2800 General Neuroscience
11359 Institute for Regenerative Medicine (IREM)
Middle Aged
medicine.disease
Endocrinology
2728 Neurology (clinical)
chemistry
Case-Control Studies
ABCA1
Immunology
biology.protein
ATP-Binding Cassette Transporters
Female
lipids (amino acids
peptides
and proteins)
Neurology (clinical)
Geriatrics and Gerontology
Alzheimer's disease
Age of onset
Switzerland
ATP Binding Cassette Transporter 1
Developmental Biology
DOI: 10.5167/uzh-50350
Popis: Increased formation of the beta-amyloid peptide (Abeta) is a central event in the pathogenesis of Alzheimer's disease (AD). High cellular cholesterol load promotes Abeta formation. The ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol efflux from cells. We hypothesized that genetic variability in ABCA1 may influence cholesterol metabolism in the central nervous system (CNS) and, thus, interfere with the development of AD. Healthy elderly carriers of the A allele of a non-synonymous (R219K) single nucleotide polymorphism (SNP) in the ABCA1 gene (rs2234884) had on average 33% lower total cholesterol in cerebrospinal fluid (CSF) than non-carriers. In 169 patients with late onset, sporadic AD, this allele was associated with delayed age at onset of the disease by 1.7 years on average. Rs2234884 and another non-synonymous SNP (R1587K) in ABCA1 (rs2234886) failed to show significant association with the risk for AD. We conclude that genetic variability of ABCA1 influences the development of AD, possibly by interfering with CNS cholesterol homeostasis.
Databáze: OpenAIRE
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