Biotechnology Neuroscience

Alzheimer’s disease, How close are we in curing it?

Many neurological diseases arise due to blockage of blood towards to brain. There are several factors for these neurological diseases. Some are due to trauma to the head. On the other hand, some are pre-dispose to it. In some instances, such disorders occur due to deteriorating health conditions associated with old age. One such disease is Alzheimer’s disease or AD – a progressive fatal disease.

Types of AD

Alzheimer’s can affect patients through a plethora of ways. For instance, like physically, mentally, emotionally and socially.  Additionally, there are three different stages of the disease. They are the early stage (first year or two), middle stage (second to fifth years), and the late-stage (fifth years and after). Alzheimer’s has three main types; late-onset Alzheimer’s disease (LOAD), early-onset Alzheimer’s disease (EOAD), and Familial Alzheimer’s disease (FAD).

  • Early-onset Alzheimer’s disease, (EOAD): this type comes before the age of 65
  • Late-onset Alzheimer’s disease, (LOAD): this type comes after exceeding 65 years.
  • Familial Alzheimer’s disease (FAD): This type of Alzheimer’s disease runs in the family and it is hereditary.

 

Comparison between a normal brain and Alzheimer's Brain.
Comparison between a normal brain and Alzheimer’s brain. Source: Wikimedia

Genetics of Alzheimer Disease

Alzheimer disease (AD) is the fourth leading cause of death in adults. The incidence of the disease rises steeply with age. AD is twice more common in women than in men. Incidence of such a disease increases with age; meaning it comes steeply to old people, and it is the fourth leading cause of death in adults.

The disease also runs in families, and there are many mutations responsible for causing AD. However, the most common mutations are located on four main genes. They are located on chromosomes with numbers 1, 14, 19, and 21. Some of the genes active in Alzheimer’s are APP, PSEN1, PSEN2 however the most common gene is APOE.  APOE is also more active in LOAD than in EOAD. FAD occurs more than the other two types.

One of the most obvious symptoms of AD is the decline in memory and other motor functions, which result in social impairment. AD results in a high percentage of dementias, Decline in cognitive abilities and memory loss are key symptoms of it.

Causes of Alzheimer Disease

There are many causes for AD, first and the most important cause is the accumulation of the T protein (TAU protein) which form neurofibrillary tangles and neuritic plaques. The second thing is the building up of the APP (abnormal precursor protein). This protein is responsible for the processing of amyloid-beta protein in the central nervous system. It’s a complex cell surface protein found nearly all over the human body.

Amyloid-beta protein is consisted of many other domains and linkers flexibly connect these domains. Its building up and accumulation results in dementia. This also results in malfunctioning of several processes like reasoning, remembering, thinking, and many other behavioral abilities, which lead to disturbances in the daily routine of those affected patients.

Injuries to the brain result in the production of beta-amyloid. But due to a mutation in this gene. Instead of functioning properly, it begins to accumulate in the brain. Afterward, these mutated proteins further damage to brain cells in the form of plaques and tangles of beta-amyloid protein. Hence, changes occur in the structure of the brain and this results in the death of brain cells. Researchers believe that a combination between both environmental and genetic risk factors increases the risk for AD.

Genetic factors

There are around 30000 genes present in the 23 human chromosome pairs and those causing the FAD are:

  • Amyloid precursor protein (APP):

Its gene is present on chromosome 21 with mutations lead to an inherited form of AD.

  • Presenilin-1 (PS-1):

The location of this gene is on chromosome 14 and this one is the most common cause of inherited AD.

  • Presenilin-2 (PS-2):

This one is present on chromosome 1.

  • Apolipoprotein E-e4 (APOE4):

According to recent studies, Researchers find out that there is an increased risk for AD caused by APOE4 which is located on the 19th chromosome.

 Environmental factors

  • Aluminum:

Aluminum is a common element which is found in diverse types of food such as potatoes, and it’s also found in numerous household products. It is found out that accumulation of aluminum over time leads to neurotoxicity and it can also trigger Alzheimer’s.

  • Sleep Deprivation:

Researchers at the University of Washington concluded that adults who don’t sleep well are at a higher risk to have AD, and this has been concluded after experimenting Vivo microdialysis to notice that amyloid-beta protein increases in when mice aware mostly in the night.

Video: What you can do to prevent Alzheimer’s | Lisa Genova

Diagnosis of Alzheimer’s Disease

  •  Neuropsychological tests:

For neuropsychological deficits, several tests are performed.  Mainly the aim of these tests to judge the memory retention capabilities of the patients, their temporal and spatial judgment, decision making, motor movements. These tests tell about the relationship between brain, behavior and the patient.

  • Brain-imaging scans:

These scans tell about the structural abnormalities of the brain. The presence of tangles and plaques of Tau and beta-amyloid proteins and physical damage done to the brain. Most commonly use brain-imaging techniques are Computed tomography (CT), structural magnetic resonance imaging, and positron emission tomography (PET).

with the help of radioactive labels, we can tell the levels of tau proteins, which in turn tell us about the progression level of Alzheimer’s disease.

 

Progression levels of Alzheimer’s disease. Source: Swarbrick, S., Wragg, N., Ghosh, S. et al

Possible Treatments for Alzheimer’s Disease

Unfortunately, there are no available treatments for Alzheimer’s disease.  However, researchers spare no effort to discover new ways and novel target sites to decrease and reduce its progression. Even though we can’t stop its progression, but its rate can be decreased in many different ways. For example, three cholinesterase inhibitors enzymes; donepezil, galantamine, and rivastigmine helps in reduction of its progression rate. Moreover, chemicals like N-methyl-D-aspartate (NMDA) receptor antagonist and the anti-amyloid disease-modifying treatment also show some success in reducing progression rate.

There are several ways in which researchers are trying to cure Alzheimer’s. They are targetting several factors, aiming to reduce and stop the progression of Alzheimer’s Disease.

  •  Medication Treatment

Currently, there are two types of medication use for the treatment purpose;

  • Acetylcholinesterase inhibitors
  • NMDA receptor antagonists

Unfortunately, the National Institute for Health and Care Excellence (NICE) has reviewed the trials and the results were mixed with just 40% of positive impact from such a treatment.

  • Herbal remedies, dietary supplements, and “medical foods” Treatments

Several alternative medications which allegedly use as memory enhancers to stop the progression of Alzheimer’s disease. However, the FDA does not approve of them because of their unknown safety and effectiveness.

  • Stem cells therapy for Alzheimer’s disease

Stem cell therapy holds immense potential for treating neurodegenerative diseases like Alzheimer’s disease.  AD destroys the brain cells, so with the help of stem cells, we can again successfully regenerate those cells. Furthermore, In animal models, stem cell therapy successfully increased the levels of synaptic proteins. This tells us that stem cell therapy indeed will be a possible treatment for Alzheimer’s disease. On the other hand, currently, research is underway in this field to find out how to properly control the molecular mechanism of these stem cells. So that they can work without any problem.

  • Nanoparticles Treatment of Alzheimer’s disease

Nanoparticles are an excellent way of carrying drugs and other chemicals inside the body. It can carry to those parts of the body, where normally drugs are unable to reach easily.  Similarly, research is currently underway on using nanoparticles to target tangles of tau protein and plaques of beta-amyloid protein.

 

  • miRNA-mediated gene silencing genetic therapy for Alzheimer’s disease

miRNA are small non-coding RNA, they range from 22-23 nucleotides. They have a major function in regulating gene expression. They bind to UTR and block the translation in mRNA and suppresses the gene expression.

Several miRNA helps in the expression of several proteins, which directly plays a role in the pathogenesis of AD. Therefore, silencing these miRNA will become a possible treatment for Alzheimer’s disease as well as for other neurodegenerative diseases shortly.

Read more:  11 Diseases CRISPR Technology Could Cure!

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