Navigation Links
A new factor of genetic susceptibility to Alzheimer's disease
Date:11/19/2012

A large-scale international study involving French researchers from the Inserm-Institut Pasteur Lille-Universit Lille Nord de France "Public health and molecular epidemiology of ageing-related diseases" joint research unit led by Philippe Amouyel, has just discovered a gene for susceptibility to a rare disease that causes susceptibility to a common one, Alzheimer's disease, providing evidence of the heterogeneous aetiology of Alzheimer's disease.

This whole-exome sequencing approach is explained in detail in The New England Journal of Medicine dated 14 November 2012.

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, or Nasu-Hakola disease, is a genetic disorder passed on by means of autosomal recessive transmission. The disease starts at the age of around 30 years with pains in the wrists or shoulders associated with swollen joints. Bone fractures can occur as a result of minor traumas. Bone x-rays show epiphyseal cysts. Slight personality changes then occur followed by frontal neurological signs (euphoria, loss of social inhibitions) evolving into early-onset dementia. The disorder has been associated with mutations of the TREM2 (Triggering Receptor Expressed on Myeloid cells 2) gene on chromosome 6.

British, American and French researchers have now shown that on this same region of chromosome 6, mutations of the TREM2 gene were associated with a five times greater risk of developing late-onset Alzheimer's disease. A complete sequencing was performed on 281 individuals with Alzheimer's disease and 504 controls. Analysis of the TREM2 gene showed excessive TREM2 mutations in those with the disease compared with the control subjects. Characterisation of one of these TREM2 mutations in very large sample populations of patients with Alzheimer's disease has allowed researchers to measure precisely the importance of this association between TREM2 mutations and the disease. Finally, a replication study was performed in another independent series of 1994 cases and 4602 controls, which confirmed this strong association (OR=4.97 CI 95% [2.42-10.21], P<6.10-6).

These results are also confirmed in the same edition of The New England Journal of Medicine by an Icelandic team, which also shows that this gene is a risk factor for Alzheimer's disease in the Finnish population and other European populations.

A pathological analysis of six individuals presenting variants of the TREM2 gene has revealed evidence of Alzheimer's-type brain lesions. The study of TREM2 gene expression in normal human brains has shown high levels in the white matter and in the hippocampus and cortex.

In a transgenic mouse model of Alzheimer's disease, an increase in TREM2 expression was observed in microglial cells surrounding the amyloid plaques and the neurons compared with normal mice. The TREM2 gene encodes a protein that participates in the activation of immune responses in macrophages and dendritic cells.

This discovery has two main consequences. Firstly, this observation provides a better understanding of the immune system's involvement in Alzheimer's disease in which the gene of complement receptor 1 (CR1) had already been implicated, in previous work by Inserm-Lille2-IPL UMR744 . Furthermore, this approach of whole-exome sequencing has allowed the discovery of a gene for susceptibility to a rare disease that causes susceptibility to a common disease, evidence of the heterogeneous aetiology of Alzheimer's disease. It is the loss of function of this gene in its homozygous or heterozygous variants that determines the nature of the disorder.

These results, which demonstrate how much progress has been made in understanding Alzheimer's disease, involved teams from LabEx DISTALZ, and were able to be produced partly through the support of the French Foundation for Scientific Cooperation on Alzheimer's and similar diseases, launched in February 2008.
'/>"/>

Contact: presse
presse@inserm.fr
INSERM (Institut national de la sant et de la recherche mdicale)
Source:Eurekalert

Related medicine news :

1. Early Menstruation Tied to Factors That Raise Heart Disease Risk
2. Social environmental factors affect rehospitalization risk in home healthcare patients
3. Many U.S. Hispanics Have Heart Disease Risk Factors
4. Fat molecule ceramide may factor in muscle loss in older adults
5. Smoking and hyperactivity share common genetic risk factor
6. Atrial fibrillation is a modifiable risk factor for stroke
7. Risk factors in hospital readmissions among general surgery patients identified in study
8. Money key factor in driving med students from primary care careers
9. Scientists Focus on Factors Behind Asthma Attacks
10. Age, not underlying diagnosis, key factor in weight gain in children after tonsillectomy
11. New genetic risk factor for inflammation identified in African-American women
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... Global Healthcare ... scenic Alexandria Park in Milford, NJ. This free event, sponsored by Global Healthcare ... activity. The fun run is geared towards children of all ages; it is ...
(Date:10/13/2017)... ... October 13, 2017 , ... “The Journey: From the Mountains to the ... save lost souls in the Philippines. “The Journey: From the Mountains to the Mission ... of the Bible. She has taught all ages and currently teaches a class of ...
(Date:10/12/2017)... LA (PRWEB) , ... October 12, 2017 , ... Planet ... in the U.S., announced today its plans to open a flagship location in Covington, ... occupy the former Rooms To Go store next to Office Depot in the Holiday ...
(Date:10/12/2017)... ... October 12, 2017 , ... Asante, a nationally recognized health ... expanded their existing home health joint venture through an agreement, effective October 1, ... joint venture home health company with Asante, delivering clinically integrated care, for the ...
(Date:10/12/2017)... ... 2017 , ... Leading pediatric oncology experts at Children’s National Health System ... Congress of the International Society of Paediatric Oncology (SIOP) Oct. 12-15. Chaired by ... and Blood Disorders at Children’s National, and Stephen P. Hunger, M.D., Chief of ...
Breaking Medicine News(10 mins):
(Date:10/12/2017)... Oct. 12, 2017   Divoti USA will ... to the standard of the latest FDA requirements, which stipulates new ... Anyone in need of Medical ID jewelry such as Medical ... are engraved in terms of the new FDA requirements ... Divoti offers this dark ...
(Date:10/11/2017)... , Oct. 11, 2017  True Health, a ... amplified its effort during National Breast Cancer Awareness ... cancer risks. ... Oncology calculated that more than 10 million American ... mutations in BRCA1 or BRCA2 and have not had ...
(Date:10/7/2017)... 2017   Provista, a proven leader in ... in purchasing power, today announced a new resource area ... Newsroom is the online home for case studies, ... bios, news releases, slideshows and events. ... of resources at their fingertips, viewers can also watch ...
Breaking Medicine Technology: