Cutting Edge: An early warning system for Alzheimer’s?

Can we detect Alzheimer’s early enough through gene coding? A Gujarat Biotechnology Research Centre (GBRC) study has found a variation in the AChE gene that could be linked to early onset but needs further investigation to be recognised as a definitive diagnostic module.
As part of the Gandhinagar-based Gujarat Biotechnology Research Centre’s (GBRC) broader scope of work towards developing an early diagnostic kit for Alzheimer’s disease, a study of a small cohort of 43 DNA samples has found a correlation between a protein-coding gene variant and the disease. However, given the small sample size of the study GBRC, the Hospital of Mental Health and the Institute of Mental Health in Ahmedabad — 32 diagnosed Alzheimer’s disease patients and 11 healthy individuals as control group — the correlation may not be equated to causation at this stage.
If a significant causation is linked through future large-scale studies, it would be a breakthrough of sorts. For it would mean that if an individual’s genetic coding shows the AChE variation, he/she may run the risk of Alzheimer’s. This could then be useful as an early warning system.
Alzheimer’s disease, a progressive neuro-degenerative disorder, is classified into two broad groups. Early onset happens in people aged below 65, usually between 40s and 50s. Late onset is seen in the 65-plus age group.Best of Express PremiumPremiumPremiumPremiumPremium
The pre-print paper, which has not been peer-reviewed yet, took DNA samples from 32 patients diagnosed with Alzheimer’s with no family hory of dementia from various mental health hospitals of Gujarat, namely, Hospital of Mental Health in Ahmedabad, Bhuj and Vadodara. The average age of the patient sample was 68.11 years, test cases ranging from 52 to 79 years. DNA samples from 11 other healthy individuals were also taken as a control group. All 43 DNA samples were sequenced and analysed.
The study notes that three genes — amyloid precursor protein (APP), which is expressed in tissues and is concentrated in synapses of neurons, presenilin1 (PSEN1), and presenilin2 (PSEN2) — have been linked with early onset autosomal dominant Alzheimer disease. But the next generation sequencing now suggests that the “frequency of mutations in these genes varies dramatically among populations, with genetic background playing a profound impact in this variance.”
Because of a lack of data and studies from the Indian context in this regard, on how the genetic mutations may vary in the Indian and Gujarat’s population, the study established a basic association using targetted sequencing of 94 genes, which were identified on exing literature review.
The single nucleotide polymorphism analysis, which looks at variation in a genetic sequence that affects only one of the four basic building blocks of DNA, found that the AChE gene, which encodes an enzyme that is responsible for breakdown of neurotransmitters, has a link with Alzheimer’s Disease. This, the authors of the paper claim, is a first, as according to them, “There is currently no literature on AChE and its variants that have a role in Alzheimer’s disease.”
GBRC director, Prof Chaitanya Joshi, who is a co-author of the study, told The Indian Express that it is too early to say whether the correlation is associated with early or late onset of the disease. He also noted sample size as one of the limitations of the study. “We need to increase the number of patients in the study, and if the same AChE variation is seen then, we can say this result is significant.”
Senior genetic counsellor at Apollo Hospitals in Ahmedabad Reena Trivedi said that genetic testing is not par for the course in Alzheimer’s diagnosis, especially in late onset cases which are generally age-related. She added that even for early onset, a mutational variation need not be indicative of an individual’s vulnerability to one specific disorder. “It is not a common practice among neurologs to get genetic testing done for Alzheimer’s. Perhaps when someone young shows signs, genetic testing is done. Generally, when a disease has an early onset, we assume it is inherited, possibly due to a genetic mutation that may be running in the family. Alzheimer’s is usually clinically identified and is symptomatically treated. But if there is a genetic mutation that has been discovered early and then they find out it is running in the family, then the offspring and siblings of the patient are also tested for the mutation. However, any change is not diagnostic or suggestive of any perfect disorder-causing variant. The mutation can also be due to a normal change in the (genetic coding) of the population, or in people of a particular group. In terms of genetic study done worldwide so far, we have discovered 22,000 genes, covered 88,000 clinically relevant genes and know about 8,000 disorders which are caused those,” said Trivedi.