Alzheimer’s Research: Are We a Step Closer to Early Diagnosis?

Alzheimer’s is a progressive disorder that causes brain cells to waste away (degenerate) and die.

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Alzheimer’s is a progressive disorder that causes brain cells to waste away (degenerate) and die.
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Every four seconds, someone in the world is diagnosed with Alzheimer’s. The disease is the major cause of dementia, which affects more than 50 million people worldwide.

Alzheimer’s disease is an irreversible, progressive brain disease that slowly destroys memory and thinking skills, and eventually, the ability to carry out the simplest tasks of daily living.

The World Health Organization says, by 2030, the number of people suffering from Alzheimer’s is set to double and it will triple by 2050.

The degenerative neurological disorder is yet not fully understood. Memory loss is a key symptom of this disease. As it progresses, remembering things becomes more difficult and more symptoms start showing up.

Current Methods Of Diagnosis & Treatment

Although scientists are learning more every day, right now, they still do not know what causes Alzheimer’s disease.

Certain lifestyle choices such as eating a healthy balanced diet, exercising and getting enough sleep could help maintain healthy brain activity and possibly even delay the onset of memory disorders like Alzheimer's and Dementia. But, there is no strong evidence that even these measures could prevent either of the illnesses altogether.

The most definite way of diagnosing Alzheimer’s, until this century, was autopsy after the death of the person, by finding certain levels of two specific lesions, or areas of abnormal tissue, according to a report in The Conversation. Those two lesions are beta-amyloid plaques and neurofibrillary tangles.

At present, these are some of the methods involved in the diagnosis of the disorder:

  • Cognitive assessment which involves answering questions and solving puzzles
  • Physical, neurological and neurophysical examination
  • MRI scans to monitor brain networks
  • PET scan for different forms of dementia to look into various brain regions using imaging
  • Specialised tests metabolic markers, vitamin levels, endocrine assessment, infection and tumour markers
  • Electroencephalogram (EEG), in which electrodes are placed on the scalp to identify the stage of the disease and rule out other dementias

Blood Tests

Researchers have been trying to devise blood tests to detect the abnormal presence of two key biomarkers, amyloid and tau proteins, in the brain as an indication of Alzheimer’s. The challenge is for these tests to be sensitive and specific enough - and there is some good news here.

For instance, a new blood test for Alzheimer’s has been able to detect the illness as accurately as other more expensive and invasive methods, The New York Times reported on Tuesday, 28 July.

The promising test could determine whether people with dementia had Alzheimer’s instead of another condition, and could identify signs of the disease almost 20 years before memory and thinking problems are expected to show up in the patients.

This newly developed test measures a form of the tau protein found in the brain in Alzheimer’s and showed better results than MRI brain scans; was equally good as PET scans or spinal taps and was ‘nearly as accurate’ as autopsies - which is the most accurate diagnostic method. Researchers found that measuring this protein, p-tau217, could predict Alzheimer's dementia with 96% accuracy, BBC reported.

Scientists believe that blood tests such as this would help speed up the search for new therapies by making it ‘faster and cheaper to screen participants for clinical trials’.

Medicines & Treatment

Currently, there is no cure for the disease, but there are drugs available to alleviate symptoms, improve cognitive abilities and delay functional decline. There are also medicines available to regulate the activity of chemical messengers in the brain, and medical treatments available for behavioral problems that accompany Alzheimer’s.

The real challenge in developing treatments and drugs for Alzheimer’s is the inability to diagnose it in its early stages.

Approving a medication requires clinical trials, which need participation from people diagnosed with the disease. But when patients enrolled in them are too far advanced in their illness, they cannot be ideal participants as there is enough damage in the brain already.

This is the reason why blood tests for early detection of Alzheimer’s show promise. They can be relatively cheaper, less invasive, convenient and timely.

According to a Mayo Clinic report, “Future Alzheimer's treatments may include a combination of medications, similar to how treatments for many cancers or HIV/AIDS include more than a single drug.”

Several treatments in development aim to target clumps of plaque using various approaches, such as deploying antibodies which recruite the immune system, preventing the destruction of connections between nerve cells (synapses) in the brain, and blocking the production of a parent protein. Similarly, other drugs, as well as vaccines, aim to prevent the tau protein from tangling and causing brain abnormalities. Other than this, researchers are also looking at approaches to study the effects of insulin resistance on the brain, inflammation, repurposing drugs used for blood pressure and vascular disease, and hormone therapy for women - although research is still ongoing for each of these.

Alzheimer’s Vaccine?

A preventive treatment for dementia may proceed to clinical trials after successful animal testing, say researchers. The research is looking to develop effective immunotherapy through a new vaccine to remove the protein aggregates linked to Alzheimer’s disease, reported news agency IANS.

Recent success in bigenic mice models supports progression to human trials in years to come, the research added.

The study, published in the journal Alzheimer's Research & Therapy paves the way for more work in the future. The researchers tested the universal MultiTEP platform-based vaccines formulated in the adjuvant developed at Australian lab.

The research team says in a report, “Current therapeutic approaches have primarily aimed to reduce pathological aggregates of either Aβ or tau, yet phase 3 clinical trials of these approaches have thus far failed to delay disease progression in humans.” The scientists believe that “combinatorial therapies that concurrently target both Aβ and tau might be needed for effective disease modification.”

“Taken together, these findings warrant further development of this dual vaccination strategy based on the MultiTEP technology for ultimate testing in human Alzheimer’s disease.”
Study lead authors Professor Anahit Ghochikyan and Mathew Blurton-Jones

Professor Petrovsky said the Advax adjuvant method is a pivotal system to help take the combination MultiTEP-based Aß/tau vaccines therapy, as well as separate vaccines targeting these pathological molecules, to clinical trials - perhaps within two years.

“Our approach is looking to cover all bases and get past previous roadblocks in finding a therapy to slow the accumulation of Aß/tau molecules and delay Alzheimer’s disease progression in a the rising number of people around the world.”
Professor Anahit Ghochikyan and Mathew Blurton-Jones

A recent report on human monoclonal antibody, aducanumab, showed that its high dose of this antibody reduced clinical decline in patients with early Alzheimer's disease as measured by primary and secondary endpoints. But it could not be used as a preventive measure in healthy subjects due to the need for frequent (monthly) administration of high concentrations of the immunotherapeutic.

(With inputs from IANS)

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