Early warning gene signature for Alzheimer's

DNA
A depiction of the double helical structure of DNA. Its four coding units (A, T, C, G) are color-coded in pink, orange, purple and yellow. Credit: NHGRI

A 'gene signature' that could be used to predict the onset of diseases, such as Alzheimer's, years in advance has been developed in research published in the open access journal Genome Biology.

The study aimed to define a set of associated with 'healthy ageing' in 65 year olds. Such a molecular profile could be useful for distinguishing people at earlier risk of age-related diseases. This could improve upon the use of and complement traditional indicators of disease, such as blood pressure.

Lead author James Timmons, from King's College London, UK, said: "We use birth year, or chronological age, to judge everything from insurance premiums to whether you get a medical procedure or not. Most people accept that all 60 year olds are not the same, but there has been no reliable test for underlying 'biological age'.

"Our discovery provides the first robust molecular 'signature' of biological age in humans and should be able to transform the way that 'age' is used to make medical decisions. This includes identifying those more likely to be at risk of Alzheimer's, as catching those at 'early' risk is key to evaluating potential treatments."

The researchers analyzed the RNA of healthy 65 year old subjects, and used the information to develop a signature of 150 RNA genes that indicated 'healthy ageing'. The signature was found to be a reliable predictor for risk of age-related disease when studying RNA from tissues including human muscle, brain and skin.

With this RNA signature, they developed a 'healthy age gene score' which they used to test and compare the RNA profiles of different individuals, and demonstrated that a greater score was associated with better health in men and women.

The researchers studied RNA from healthy 70 year old subjects and analyzed follow-up health data over two decades. Despite all subjects being born within a year of each other, their RNA at around 70 years of age demonstrated a very wide distribution in 'healthy age gene score', varying over a four-fold range. This variation was shown to link to . A greater gene score was also associated with better cognitive health and renal function across a 12 year span - both important determinants of mortality.

In particular, they demonstrated that patients diagnosed with Alzheimer's Disease had an altered 'healthy ageing' RNA signature in their blood, and therefore a lower healthy age gene score, suggesting significant association with the disease.

Timmons added: "This is the first blood test of its kind that has shown that the same set of molecules are regulated in both the blood and the brain regions associated with dementia, and it can help contribute to a dementia diagnosis. This also provides strong evidence that dementia in humans could be called a type of 'accelerated ageing' or 'failure to activate the healthy ageing program'."

Given that early intervention is important in Alzheimer's and there is a need to identify those at greatest risk, the authors say that their 'healthy age gene score' could be integrated to help decide which middle-aged subjects could be offered entry into a preventative clinical trial many years before the clinical expression of Alzheimer's.


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More information: A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status, Sanjana Sood, Iain J. Gallagher, Katie Lunnon, Eric Rullman, Aoife Keohane, Hannah Crossland, Bethan E. Phillips, Tommy Cederholm, Thomas Jensen, Luc JC van Loon, Lars Lannfelt, William E. Kraus, Philip J. Atherton, Robert Howard, Thomas Gustafsson, Angela Hodges and James A. Timmons, Genome Biology 2015. DOI: 10.1186/s13059-015-0750-x
Journal information: Genome Biology

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Citation: Early warning gene signature for Alzheimer's (2015, September 6) retrieved 23 August 2019 from https://medicalxpress.com/news/2015-09-early-gene-signature-alzheimer.html
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JVK
Sep 06, 2015
Excerpt: "Timmons added: "This is the first blood test of its kind that has shown that the same set of molecules are regulated in both the blood and the brain regions associated with dementia, and it can help contribute to a dementia diagnosis."

What set of molecules links ecological variation to ecological adaptation via RNA-mediated events that link atoms to ecosystems via the nutrient-dependent physiology of reproduction in all genera?

http://www.genome...16/1/185 Journal article conclusion: We did not note any significant ontology pathway enrichment within our healthy ageing diagnostic gene lists (Fig. 6a). Thus, we cannot neatly place the genes that contribute to the healthy physiological age diagnostic into a convenient canonical signaling pathway.

Sep 06, 2015
Conclusions
"We identify a novel and statistically robust multi-tissue RNA signature of human healthy ageing that can act as a diagnostic of future health, using only a peripheral blood sample. This RNA signature has great potential to assist research aimed at finding treatments for and/or management of AD and other ageing-related conditions."
http://www.genome...16/1/185

The two studies complement each other, they are not at odds.

JVK
Sep 06, 2015
I asked: "What set of molecules links ecological variation to ecological adaptation via RNA-mediated events that link atoms to ecosystems via the nutrient-dependent physiology of reproduction in all genera? "

See also: A Genome-Wide Scan Reveals Important Roles of DNA Methylation in Human Longevity by Regulating Age-Related Disease Genes http://journals.p....0120388

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