Five new genetic susceptibility factors identified for Alzheimer’s disease

Alzheimer’s is the leading cause of memory disorders and intellectual functions among elderly people and represents a major public health issue.

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European researchers are pooling their strengths to combat this disease more quickly and efficiently. As a result, a consortium of 108 European laboratories coordinated by a French team (“Public Health and molecular epidemiology of diseases related to aging” UMR 744 Inserm-Lille-Institut Pasteur de Lille) and a British team (Centre for Genetic and Genomic Neuropsychiatry, University of Cardiff) have recently identified five new genetic predisposition factors involved in the development of the disease.

The research was conducted by Inserm in close collaboration with the CEA (French national genotyping centre, CEA-IG-CNG), the Fondation Jean Dausset-CEPH and a European consortium of 25 teams.

The discoveries were made thanks to support from the Fondation Plan Alzheimer, which coordinated the research section of the plan, launched in February 2008, to fight Alzheimer’s and other related diseases.

In September 2009, the research undertaken by these French and British teams uncovered three new genetic susceptibility factors for Alzheimer’s disease (CLU, CR1, PICALM) in addition to the apolipoprotein-coding gene allele ε4 (APOA) discovered over 15 years ago.

In this new study, the researchers analysed the genomes of 59,176 individuals, 19,870 of whom suffered from Alzheimer's disease; the analysis led to the discovery of five new predisposition genes: ABCA7, MS4A, EPHA1, CD2AP and CD33. The researchers also confirmed the importance of the BIN1 gene. These results are published in the online version of Nature Genetics dated 3 April 2011.

The results present two key advantages. Firstly, the identification of new genes associated with Alzheimer’s disease will expand the number of research hypotheses on the causes of the illness. This stage is essential since it paves the way to identify new channels for curative treatments (current medication only has symptomatic effects). Secondly, the genes identified through this research will help to improve the definition of individual ‘terrain’ that favours the development of Alzheimer’s disease and will provide valuable help when preventive treatments become available. Knowledge of these genes will help researchers from across the globe to better understand Alzheimer trigger events that precede the characteristic destruction of nerve cells and the loss of intellectual functions.

In the same edition of Nature Genetics, a US consortium coordinated by the University of Pennsylvania also identified four of these genes in a population comparing more than 11,000 patients with an equivalent number of healthy individuals. All the researchers from Europe and the US who contributed to these discoveries met for the first time in Paris in November 2010 to create the world IGAP consortium (International Genomics Alzheimer Project) funded by the Fondation Plan Alzheimer in France and the Alzheimer’s Association in the US. "This unique global initiative will boost the fight against the disease and underline the importance of international collaborative studies to tackle the complexities of this kind of illness" indicates Philippe Amouyel, its coordinator for France and the International Consortium.

Alzheimer’s disease is one of the main causes of dependency among the elderly. It results from neurone degradation in different areas of the brain. Its symptoms include increased alterations to memory, cognitive functions and behaviour disorders that lead to a progressive loss of independence. In France, Alzheimer’s disease affects more than 850,000 people and represents major social and economic costs.
Alzheimer’s disease is characterized by the development in the brain of two types of lesions: amyloid plaques and neurofibrillary degeneration. Amyloid plaques originate from the extracellular accumulation of a peptide, the β amyloid (Aβ) peptide, in specific areas of the brain. Neurofibrillary degeneration is characterized by intra-neuronal lesions caused by the abnormal aggregation of the Tau protein in the form of filaments.
Identifying genes that participate in the incidence of Alzheimer’s disease and its development will make it possible to tackle the phsyiopathological mechanisms behind this affliction more rapidly, to identify the target metabolic channels for new treatments and to provide a means of identifying individuals that are most at risk when effective preventive treatments become available.

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Source

“Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease”

Paul Hollingworth et al.
Nature Genetics, April 3rd 2011

Research contact

Philippe Amouyel
Director of Inserm Unit 744 "Public health and molecular epidemiology of aging-related illnesses"
Tel.: +33 (0)6 86 43 23 34