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Plaques In The Brain May Cause Alzheimer's Disease, Study Reveals

One of the most common kinds of dementia, Alzheimer's Disease (AD) is a neurodegenerative disease. While the symptoms are often quite mild at the onset of the disease, they gradually progress to take on a more severe form.

Several theories have been put forward to account for why some people are more predisposed to getting AD than the rest, with some of the most common causes of the condition being advanced age, dysfunction of the immune system, genetic factors and environmental factors such as exposure to aluminium etc.

According to the National Center for Biotechnology Information (NCBI), depending on the level of cognitive impairment, AD is classified into preclinical, mild, moderate, and late-stage. As an incurable disorder, the therapeutic options available for AD have revolved around reducing the symptoms and checking the rate of progression of damage [1] [2] .

Prevention is undoubtedly a much better solution for tackling AD. Precise diagnosis, as early as possible, is probably the best line of defence. Generally, antidepressants and anti-psychotics are given to patients with confirmed AD [3] .

Consequently, a recent study focused on exploring the possible role plaques play in the development of Alzheimer's.

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Memory Decline Begins Before The Build-up Of Plaques

Scientists, researchers and health professionals have been aware of the fact that Alzheimer's disease is accompanied by the buildup of clumps of amyloid protein between brain cells. However, there has been an ambiguity regarding where the plaque build-up was causing the condition.

The prevailing theory which substantiated that an individual undergoes memory decline after the amyloid plaques begin to appear in the brain was discredited by the study published in the journal Neurology.

In a recent study, researchers asserted that the early declines in memory and thinking reported in Alzheimer's patients tend to occur before amyloid plaques begin to appear in the brain and not after.

The head researcher pointed out, "our study was able to detect subtle thinking and memory differences in study participants and these participants had faster amyloid accumulation on brain scans over time, suggesting that amyloid may not necessarily come first in the Alzheimer's disease process."

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The Focus Has To Be Shifted From Amyloid

Until now, studies on Alzheimer's diseases were solely focused on exploring the role of amyloid - a protein that is deposited in the liver, kidneys, spleen, or other tissues in certain diseases. Majority of the studies focused on exploring possible treatments for Alzheimer's disease has focused on targeting amyloid. However, the recent study has opened up the need to shift focus on to other possible targets.

Consequently, these study findings were not the first to point out that amyloid plaques might not cause Alzheimer's disease. A previous study published in the New England Journal of Medicine tested the impact of verubecestat (an experimental Alzheimer's drug) and was found that the drug reduced amyloid plaque levels in patients' brains and spinal fluid.

However, the reduction in the level of plaque build-up did not cause the patients to show any easing or slowing of their disease. The researcher went on to say that, "these results suggested that amyloid lowering is the wrong target. Although the medicine has been hitting the targets, individuals suffering from the condition showed no improvement and some even got worse, both in terms of brain structure and brain cognition.

Similar poor results were seen with another amyloid-focused drug, aducanumab and were halted due to the ineffectiveness of it and are in the talks of being restarted.

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The Study And Its Findings

The research team tracked the neurological health of 747 people, average age 72 years. Various tests on the cognitive health of the individuals were done and the study revealed that 305 people were deemed to have normal thinking and memory skills, 153 had very subtle thinking and memory differences, and 289 people had mild cognitive impairment - indicating a risk of developing the condition.

The participants also underwent high-tech brain scans at the beginning of the study and then yearly scans over the next four years, to check for any signs of amyloid plaque buildup. The study also gathered the understanding that amyloid plaque accumulation occurred no faster in people with mild cognitive impairment than it did in people with normal thinking and memory skills.

Some other changes were also reported, such as faster thinning of the brain's entorhinal cortex and brain shrinkage of the hippocampus. The researcher said, "from the previous study, we know that another biomarker of Alzheimer's disease, a [brain] protein called tau, shows a consistent relationship with thinking and memory symptoms."

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More Studies Can Help Calculate The Risk For Developing Alzheimer's

The researchers pointed out the need to carry out more studies to find out and determine whether tau is already present in the brain when subtle thinking and memory differences begin to appear. In addition to that, conducting more studies on the subject could help might lead to a better way to calculate a person's risk for Alzheimer's.

"Our study demonstrated a method to successfully detect subtle differences in thinking and memory either before or during the phase when amyloid is accumulating at a faster rate," explained the researcher. "This could lead to non-invasive screenings that may be able to detect very early who are at risk of developing Alzheimer's disease.

View Article References
  1. [1] Bhuvanendran, S., Hanapi, N. A., Ahemad, N., Othman, I., Yusof, S. R., & Shaikh, M. F. (2019). Embelin, a Potent Molecule for Alzheimer's Disease: A Proof of Concept From Blood-Brain Barrier Permeability, Acetylcholinesterase Inhibition and Molecular Docking Studies. Frontiers in neuroscience, 13.
  2. [2] Mathys, H., Davila-Velderrain, J., Peng, Z., Gao, F., Mohammadi, S., Young, J. Z., ... & Martorell, A. J. (2019). Single-cell transcriptomic analysis of Alzheimer’s disease. Nature, 1.
  3. [3] Simunkova, M., Alwasel, S. H., Alhazza, I. M., Jomova, K., Kollar, V., Rusko, M., & Valko, M. (2019). Management of oxidative stress and other pathologies in Alzheimer’s disease. Archives of toxicology, 1-23.
Story first published: Thursday, January 2, 2020, 17:10 [IST]
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