Navigation Links
Study finds genes associated with hippocampal atrophy
Date:6/28/2012

(Boston) -- In a genome-wide association (GWA) study, researchers from Boston University Schools of Medicine (BUSM) and Public Health (BUSPH) have identified several genes which influence degeneration of the hippocampus, the part of the brain most associated with Alzheimer disease (AD). The study, which currently appears online as a Rapid Communication in the Annals of Neurology, demonstrates the efficacy of endophenotypes for broadening the understanding of the genetic basis of and pathways leading to AD.

AD is a progressive neurodegenerative disorder for which there are no prevention methods. Available drugs only marginally affect disease severity and progression, making AD effectively untreatable.

GWA studies using very large samples have increased the number of robust associations to 10 genes, including APOE. However, these genes account for no more than 35 percent of the inherited risk of AD and most of the genetic underpinning of the disorder remains unexplained. According to the researchers, magnetic resonance imaging (MRI) of the brain provides in vivo quantitative measures of neurodegenerative and cerebrovascular brain injury that may represent AD-related changes long before clinical symptoms appear. These measures are more powerful than comparisons of individuals with AD with cognitively healthy persons because they avoid misclassification of normal persons who will develop disease in the future.

BUSM researchers conducted a two-stage GWA study for quantitative measures of hippocampal volume (HV), total cerebral volume (TCV) and white matter hyperintensities (WMH). Brain MRI measures of HV, TCV and WMH were obtained from 981 Caucasian and 419 African-American AD cases and their cognitively normal siblings in the MIRAGE (Multi Institutional Research in Alzheimer's Genetic Epidemiology) Study. In addition, similar MRI measures were obtained from 168 AD cases, 336 individuals with mild cognitive impairment and 188 controls (all Caucasian) in the AD Neuroimaging Initiative (ADNI) Study. The MIRAGE Caucasian families and ADNI subjects were included in the first stage and the MIRAGE African American families were added in stage two. Results from the two Caucasians data sets were combined by meta-analysis.

In stage two, one genetic marker (i.e. single nucleotide polymorphism or SNP) from each of the gene regions that were most significantly associated with AD in the Caucasian data sets was evaluated in the African-American data set.

Novel genome-wide significant associations were observed for HV with SNPs in the APOE, F5/SELP, LHFP, and GCFC2 gene regions. All of these associations were supported by evidence in each data set.

"Our two-stage GWAS identified highly significant associations between a measure of degeneration in the brain region most strongly correlated with AD and several genes in both Caucasian and African American samples containing AD, cognitively impaired and cognitively healthy subjects. One of these associations was with the ε4 variant of APOE which is the most well-established genetic risk factor for AD.

Other associations were demonstrated with markers in F5/SELP, LHFP, and GCFC2, genes not previously implicated in this disease" explained senior author Lindsay Farrer, PhD, chief of biomedical genetics at BUSM. He also noted, "previous studies showed that blood level of P-selectin (the protein encoded by SELP) has been correlated with rate of cognitive decline in AD patients."

Farrer believes it is very likely that the number and specificity of these associations will increase in future studies using larger samples and focused on additional precise structural and functional MRI measures. "These findings will inform experiments designed to increase our understanding of disease-causing mechanism and may lead to new therapeutics targets," added Farrer.


'/>"/>

Contact: Gina DiGravio
gina.digravio@bmc.org
617-638-8480
Boston University Medical Center
Source:Eurekalert

Related medicine news :

1. Study Suggests Vaccine May Help Kids With Brain Cancer
2. Study reveals how cancer drug causes diabetic-like state
3. Coffee Drinking in Pregnancy Wont Lead to Sleepless Baby: Study
4. Lower GI problems plague many with rheumatoid arthritis, Mayo Clinic study finds
5. Veggies Like Broccoli, Cabbage May Help Fight Breast Cancer: Study
6. No Added Cancer Risk From Hip Replacement Materials: Study
7. Reported Decline in U.S. Pneumonia Deaths May Be False: Study
8. Early Study Finds Some Promise for Lung Cancer Vaccine
9. Narcissists Often Ace Job Interviews, Study Finds
10. Sexual objectification of female artists in music videos exists regardless of race, MU study finds
11. Soy may alleviate hot flashes in menopause, large-scale study finds
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:7/23/2017)... Melbourne, Fla. (PRWEB) , ... July 23, 2017 ... ... Stern, M.D., has joined Florida Pain Relief Group – Melbourne, a practice owned ... to board certification in interventional pain management, Dr. Stern also is certified in ...
(Date:7/22/2017)... ... July 22, 2017 , ... ... irreparable rotator cuff repairs the opportunity to return to sports and jobs that ... Orthopaedic Society for Sports Medicine’s Annual Meeting in Toronto, Ontario, Canada. ...
(Date:7/21/2017)... ... July 21, 2017 , ... Roderick ... planning services to families and business owners in northern Florida, is joining the ... provide support to area adults with developmental challenges. , The First Coast YMCA ...
(Date:7/21/2017)... ... , ... Hospital M&A activity slowed in the second quarter of 2017, according ... to 23 in the second quarter, up 15% from the 20 publicly announced acquisitions ... in the year-ago second quarter. Only four of the transactions disclosed a purchase price ...
(Date:7/21/2017)... La. (PRWEB) , ... July 21, 2017 , ... ... allow 4th-year medical students improve their chances of acceptance to a residency in ... those who have earned degrees outside the U.S. , According to data released ...
Breaking Medicine News(10 mins):
(Date:7/13/2017)... , July 13, 2017  New York City-based market ... pharmaceutical markets should be aware of.  From new products to ... are detailed in a recently completed study, Potential Pipeline ... 1.  Age-Driven Growth - ... have been aware of the impact the growing population and, ...
(Date:7/11/2017)... WHIPPANY, N.J. , July 11, 2017  Bayer has ... across eight countries as part of its prestigious Bayer Hemophilia ... Children,s Hospital of Philadelphia and Uniformed ... are among the winners. Grant recipients were announced ... Thrombosis and Hemostasis (ISTH) 2017 Congress, Berlin, Germany ...
(Date:7/11/2017)... -- Oramed Pharmaceuticals Inc. (NASDAQ: ORMP ) ... the development of oral drug delivery systems, announced today ... agreed to schedule an End-of-Phase II meeting with Oramed ... oral insulin capsule ORMD-0801 in the treatment of type ... secondary endpoints by indicating a statistically significant lowering of ...
Breaking Medicine Technology: