Neuroglobin and Alzheimer's dementia: genetic association and gene expression changes.
We previously reported strong genetic linkage on chromosome 14q to Alzheimer's disease (AD) using the presence of co-morbid hallucinations as a covariate. Those results suggested the presence of a gene increasing the risk for a genetically homogeneous form of AD characterized by the absence of comorbid hallucinations. Here we report our follow up of that study through the analysis of single nucleotide polymorphisms (SNPs) in five functional candidate genes. This work provides significant evidence of association for the gene coding for neuroglobin (NGB), a nervous system globin known to protect cells against amyloid toxicity and to attenuate the AD phenotype of transgenic mice. On further experiments we found that NGB expression is reduced with increasing age and lower in women consistent with their increased risk. NGB expression is up-regulated in the temporal lobe of AD patients consistent with a response to the disease process, as reported for NGB and hypoxia. We speculate that a compromised response due to DNA variation might increase the risk for AD. Our and others' data strongly support the involvement of NGB in AD.
Szymanski
Megan
M
McKusick Nathans Institute of Genetic Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Wang
Ruihua
R
Fallin
M Danielle
MD
Bassett
Susan S
SS
Avramopoulos
Dimitrios
D
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics*; D016022:Case-Control Studies; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005914:Globins / Q000235:genetics* / Q000378:metabolism; D006212:Hallucinations / Q000150:complications / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D000078787:Neuroglobin; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000150:complications / Q000235:genetics*; D012016:Reference Values; D012737:Sex Factors; D013702:Temporal Lobe / Q000378:metabolism
D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D005914:Globins