Research breakthrough identifies genes that increase Alzheimer’s risk

By Mark Waghorn via SWNS

Dozens of genes that increase the risk of Alzheimer's have been identified.

Many fuel rogue brain proteins known as amyloid beta and tau, say scientists.

They collect in clumps and tangles respectively - destroying neurons.

The breakthrough offers hope for new treatments for the memory-robbing disease.

Patients could be screened in middle age - and given cutting-edge gene therapy.

The findings are based on almost 800,000 people across Europe and the UK.

DNA mapping linked 75 regions, or 'loci', of the genome to the illness - 42 of which have never previously been implicated.

Co-ordinator Professor Jean-Charles Lambert, of The Pasteur Institue of Lille in France,
said: "Following this major discovery, we characterized these in order to give them meaning in relation to our clinical and biological knowledge, and thereby gain a better understanding of the cellular mechanisms and pathological processes at play."

Alzheimer's is believed to be triggered by a combination of environmental factors - such as diet and lifestyle, and mutations pre-dispose certain individuals.

The study included 111,326 people who had either been diagnosed themselves or had close relatives who had. They were compared with 677,663 healthy 'controls'.

Dementia cases worldwide are expected to triple in the next three decades to more than 150 million. Current medications only target the symptoms - not the cause.

Prof Lambert said: "A recent study estimated fewer than 100 causal common
variants may explain the entire Alzheimer's risk.

"If that estimate is correct, then our study might have already characterized a large proportion of this genetic component."

Accumulation of amyloid-beta and tau is a common feature in brain tissue from people who have died with Alzheimer's.

The study confirmed that some of the genes are involved in the production of proteins. Others block immune cells called microglia.

They lie in the central nervous system and help clear the build-up of these toxic substances.

Finally, it showed for the first time that a harmful body chemical called TNF-alpha (tumor necrosis factor-alpha) may be to blame for the advance of Alzheimer's.

The international team called for clinical trials of drugs targeting the amyloid precursor protein and TNF-alpha.

They also advised the continuation of microglial cell research initiated a few years ago - and the targeting of the TNF-alpha signaling pathway.

A genetic risk score based on the findings has been developed which can predict Alzheimer's - within three years of clinical manifestation of cognitive impairment.

Prof Lambert added: "While this tool is not at all intended for use in clinical practice at present, it could be very useful when setting up therapeutic trials in order to categorize participants according to their risk and improve the evaluation of the medications being tested."

The researchers now plan to validate and expand the results in an even broader group - and are developing numerous cellular and molecular biology approaches to determine their roles in Alzheimer's.

Gene editing replaces a target area of DNA. It has been described as a 'cut and paste' tool - removing mutations that arise when genes fuse to make an unhealthy hybrid.

The study was published in Nature Genetics.