Islamabad - Researchers have described in their research how mutations in a specific gene that codes for a neural growth factor appear to predict how quickly memory loss will progress in people with Alzheimer’s disease.

Researchers from University of Wisconsin School of Medicine in Madison recently set out to investigate whether they could identify an early marker for Alzheimer’s disease. They focused on brain-derived neurotrophic factor (BDNF), a protein coded by a gene of the same name.

BDNF is known to support nerve cells, helping them to grow, specialize, and survive. This makes it a good target for Alzheimer’s research. Earlier research has not always found solid links between levels of BDNF and Alzheimer’s, so this time, the team looked specifically at a gene mutation called the BDNF Val66Met allele, or simply Met allele.

In total, 1,023 participants - aged 55 on average - were included, and all were healthy but at risk of developing Alzheimer’s. They were followed for a maximum of 13 years. At the start of the study, blood samples were taken to test for the Met allele mutation, and it was found to be present in 32 per cent of the individuals.

All participants carried out cognitive and memory tests at the beginning of the trial and up to five more times throughout the study’s duration. Also, 140 of them underwent neuro imaging to look for beta-amyloid plaques.

The data showed that those with the Met allele mutation lost cognitive and memory skills ‘more rapidly’ when compared with those who did not have the mutation. Furthermore, individuals who carried both the mutation and plaques experienced an even quicker decline.

In verbal learning and memory tests, individuals without the gene mutation improved by 0.002 units per year, whereas those with the mutation worsened by 0.021 units each year.

Study author Ozioma Okonkwo said, “When there is no mutation, it is possible the BDNF gene, and the protein it produces are better able to be protective, thereby preserving memory and thinking skills. This is especially interesting because previous studies have shown that exercise can increase levels of BDNF.

It is critical for future studies to further investigate the role that the BDNF gene and protein have in beta-amyloid accumulation in the brain.”

Because current treatment is most successful if given earlier in the disease’s progression, this could be a vital part of the jigsaw. Okonkwo says, “Because this gene can be detected before the symptoms of Alzheimer’s start, and because this pre symptomatic phase is thought to be a critical period for treatments that could delay or prevent the disease, it could be a great target for early treatments.”

There are some shortfalls in the research. These include the fact that all participants were white, whereas various ethnicities are affected differently by the disease. For instance, African Americans appear to be more susceptible. Another shortfall of the study is that the beta-amyloid data were limited. Meanwhile, scientists from University College London and Imperial College London in the United Kingdom have identified new genetic locations that might make some people more prone to developing type 2 diabetes.

Using a UCL-developed method of genetic mapping, Maniatis and team examined large samples of European and African American people, summarizing 5,800 cases of type 2 diabetes and almost 9,700 healthy controls.

They found that the new loci - together with the ones previously identified - control the expression of more than 266 genes surrounding the genetic location of the disease.

Most of the newly discovered loci were found outside of the coding regions of these genes, but within so-called hotspots that change the expression of these genes in body fat.

Of the newly identified 111 loci, 93 (or 84 per cent) were found in both European and African American population samples.

After identifying genetic loci, the next step was to use deep sequence analysis to try to determine the genetic mutations responsible for the disease.

Maniatis and colleagues used deep sequencing to further examine three of the cross-population loci with the aim of identifying the genetic mutations. They then investigated a different sample of 94 Europeans with type 2 diabetes, as well as 94 healthy controls.

The researchers found that the three loci coincided with chromosomal regions that regulate gene expression, contain epigenetic markers, and present genetic mutations that have been suggested to cause type 2 diabetes.

Dr Winston Lau said, “Our results mean that we can now target the remaining loci on the genetic maps with deep sequencing to try and find the causal mutations within them. We are also very excited that most of the identified disease loci appear to confer risk of disease in diverse populations such as African Americans, implying our findings are likely to be universally applicable and not just confined to Europeans.”

Dr Maniatis also highlights the contribution their study brings to the research community,

“No disease with a genetic predisposition has been more intensely investigated than type 2 diabetes. We have proven the benefits of gene mapping to identify hundreds of locations where causal mutations might be across many populations, including African Americans. This provides a larger number of characterized loci for scientists to study and will allow us to build a more detailed picture of the genetic architecture of type 2 diabetes,” says the lead author.

Dr Andrew also adds, “Before we can conduct the functional studies required in order to better understand the molecular basis of this disease, we first need to identify as many plausible candidate loci as possible. Genetic maps are key to this task, by integrating the cross-platform genomic data in a biologically meaningful way.”