Fine mapping of genetic variants in BIN1, CLU, CR1 and PICALM for association with cerebrospinal fluid biomarkers for Alzheimer's disease.

• Recent genome-wide association studies of Alzheimer's disease (AD) have identified variants in BIN1, CLU, CR1 and PICALM that show replicable association with risk for disease. We have thoroughly sampled common variation in these genes, genotyping 355 variants in over 600 individuals for whom measurements of two AD biomarkers, cerebrospinal fluid (CSF) 42 amino acid amyloid beta fragments (Aβ(42)) and tau phosphorylated at threonine 181 (ptau(181)), have been obtained. Association analyses were performed to determine whether variants in BIN1, CLU, CR1 or PICALM are associated with changes in the CSF levels of these biomarkers. Despite adequate power to detect effects as small as a 1.05 fold difference, we have failed to detect evidence for association between SNPs in these genes and CSF Aβ(42) or ptau(181) levels in our sample. Our results suggest that these variants do not affect risk via a mechanism that results in a strong additive effect on CSF levels of Aβ(42) or ptau(181).

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Psykiatri (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Psychiatry (hsv//eng)

Nyckelord

Adaptor Proteins

Signal Transducing

genetics

Aged

Aged

80 and over

Alzheimer Disease

cerebrospinal fluid

genetics

Amyloid beta-Peptides

cerebrospinal fluid

Biological Markers

cerebrospinal fluid

Clusterin

genetics

Female

Genetic Predisposition to Disease

genetics

Humans

Male

Middle Aged

Monomeric Clathrin Assembly Proteins

genetics

Nuclear Proteins

genetics

Peptide Fragments

cerebrospinal fluid

Phosphorylation

Polymorphism

Single Nucleotide

Receptors

Complement 3b

genetics

Serine

metabolism

Tumor Suppressor Proteins

genetics

tau Proteins

cerebrospinal fluid

chemistry

metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)