Almost half of world’s adults aged 85 and over have Alzheimer’s Disease.
The amyloid-B precursor protein (APP) plays a key role in the development of the amyloid plaques that are the hallmark of Alzheimer’s disease. Now, researchers claim to have identified thousands of genetic variants of the APP gene that codes for the protein in the brains of patients with the most common form of Alzheimer’s disease, known as late-onset or sporadic AD (SAD).
The study reveals for the first time how this genetic variation occurs – by a mechanism involving the enzyme reverse transcriptase, the same type of enzyme used by HIV to infect cells.
APP forms plaques in the brain, as shown above in a light micrograph.
Our findings provide a scientific rationale for immediate clinical evaluations of HIV antiretroviral therapies in people with AD,’ says Jerold Chun, senior VP of Neuroscience Drug Discovery at Sanford Burnham Prebys Medical Discovery Unit (SBP), an idea that the researchers say is supported by the relative absence of proven AD in ageing HIV patients on antiretroviral medication.
The APP gene variants were created by reverse transcription, the researchers note, when RNA acts as a template to form complementary DNA sequences that are then reinserted back into the original genome.
Discovery of possible Alzheimer’s treatment. Video: Sanford Burnham Prebys Medical Discovery Institute
This process of gene recombination – which occurs each time cells divide to make new ones – has not previously been reported in nerve cells (neurons) in the brain but could also help to explain the complexity and diverse functions of our brain cells.
In recent years, novel innovation in healthcare and pharmaceuticals have hit the headlines with increasing regularity. Each story promises a better quality of life for patients and a product that will ‘revolutionise’ healthcare as we know it.
However, many of these innovations fail to materialise due to the complexity of the system. Problems with regulation, intellectual property agreements, and manufacturing are just some of the many issues that industry faces when integrating a new product into hospitals and treatment centres.
Stephen Dorrell. Image: NHS Confederation@Flickr
So, do we need rethink our expectations of innovation? Speaking at New Scientist Live in September, Stephen Dorrell, Chair of NHS Confederation and a former Health Secretary, said that as an innate characteristic of humans, innovation will not stop. However, we should be more concerned about the difficulty of making good innovation available everywhere and rethinking what we consider the most efficient way of treating patients, he said.
As the most common type of dementia – affecting one in six over the age of 80 – Alzheimer’s disease needs good innovation. With no known cure, current efforts rely heavily on having a care plan once symptoms appear and medications can only slightly improve symptoms for a time as well as slow down the progression of the disease.
Progress in pharmaceuticals
The Alzheimer’s research community are well versed in the known causes of the disease, with amyloid plaques and tau tangles the most widely accepted causes of the neurodegeneration that leads to Alzheimer’s. As a result, the majority of research and investment in the field is centred around this theory.
Neuro-Bio is a biotechnology start-up that is taking a different approach to making medicines for Alzheimer’s patients. The company is focused on a ‘previously unidentified mechanism’ of the disease that is linked to the development stages of the brain and cell death, and is working on new drug candidates that can stop the peptide involved in this mechanism from functioning improperly in adults.
After a series of setbacks in Alzheimer’s drug development, Prof Margaret Esiri, a neuropathologist at the Nuffield Department of Clinical Sciences, Oxford, said: ‘Neuro-Bio’s approach to the problem of Alzheimer’s disease is novel and scientifically well-founded. It is a good example of the new thinking that is urgently needed in this field’.
Timing it right
However, with an uncertainty for future success in Alzheimer’s pharmaceuticals, researchers interested in the genetic make-up of neurodegenerative diseases are focusing on how early diagnosis can be beneficial to patients.
Alzheimer’s can cause a significant loss of brain matter (right) compared to a healthy brain (left). Image: National Institutes of Health
According to UCL geneticist John Hardy, a loss in brain matter and amyloid build-up begins 15 to 20 years before symptoms start to appear, highlighting the need for preventative measures. This need is not consistent with what is currently available to patients in the UK however, as to qualify for a clinical trial, patients must be in the advanced stages of Alzheimer’s – often exhibiting severe symptoms that can, quite drastically, negatively affect quality of life for the individual.
Scientists at Case Western Reserve University, Ohio, US, may have solved this issue of early diagnosis after developing a machine learning program that outperforms other methods for diagnosing Alzheimer’s disease. The program integrates known disease indicators and symptoms to predict the likelihood of Alzheimer’s onset. Multiple stage comparisons, which includes associated symptoms that are not always present in Alzheimer’s, allow the program to make a more accurate prediction of who is most vulnerable.
Development of such programs could help initiatives such as the 100,000 Genomes Project which aims to provide the NHS with a new genomic medicine service that can offer better diagnosis and more personalised treatments.
Baroness Susan Greenfield. Image: National Assembly for Wales
SCI is running a Public Evening Lecture in London on Wednesday 28 February – The 21st Century mind: Blowing it, expanding it, losing it. The talk will be given by Baroness Susan Greenfield, neuroscientist and CEO of Neuro-bio. It is free to attend, but spaces are limited. Don’t miss out – booking opening soon.