Protein Build Up Causes Disorientation In Alzehimer’s Disease Patients

Experts from Columbia University Medical Center (CUMC) have linked buildup of tau protein in the brain of Alzheimer’s patients that causes spatial disorientation – inability to correctly determine body position – during the early stage of the disease.

This spatial disorientation manifests itself as unawareness of one’s surroundings and wandering.

This study, which holds a great potential in the early diagnosis and treatment for Alzheimer’s disease, was also recently published in Neuron.

According to the Alzheimer’s Association, over 5 million Americans are currently living with Alzheimer’s disease, the most commonly occurring type of dementia. One in 3 older adults are estimated to be suffering from Alzheimer’s or some other type of dementia which has now become the 6th most common cause of deaths in the US.

Researchers from CUMC estimate that three of every five Alzheimer’s disease patients experience spatial disorientation which causes a great risk to their wellbeing.

This observation was made on Alzheimer’s disease-induced mice model and can help neurologists in studying spatial orientation at the neural level.

It was also observed that the grid cells in the entorhinal cortex (EC), which play a central role in the memory formation and navigation, were mainly damaged because of this buildup.

Comparing the pathology in aged mice and control group, the adverse effects were found only in the aged mice. It was also discovered that from among the excitatory and inhibitory neurons, only the excitatory neurons were affected. The researchers analyzed the electrophysiological recording obtained in response of firing of grid cells when a movement through space was made to reach this finding.

Alzheimer’s Disease-Where Does It start In Your Head?

Over decades of research, the role of tau protein has emerged as a hallmark for the progression of Alzheimer’s disease. It has also been learnt that this neurodegenerative disease is triggered by two core factors.

At the beginning of disease pathology amyloid-β peptide (AB peptide) buildup in neural cells takes place.

In a normal person, the amyloid-β peptide is produced when a large trans-membrane protein known as amyloid precursor protein is cleaved.

The enzymatic activity in the neural cells assures that the amyloid-β peptide doesn’t accumulate in cells and is cleaved by an enzyme called -secretase into a neuro-protective molecule sAPP .

Another enzymatic pathway is carried down by two enzymes, namely  secretase and γ secretase, which cleave the amyloid-β to affirm that AB- peptide build up is not taking place in the neural cells.

However, if this catalytic activity is compromised, then the AB peptide begins to accumulate in the brain and with time manifest the symptoms of Alzheimer’s disease.

With time, the AB peptide aggregates accumulate to take forms of plagues which clog neural pathways and cause neuro-toxic effects. The AP peptides’ further interaction with certain signaling pathways in the brain also leads to phosphorylation of tau protein.

Tau protein helps in stabilizing microtubules which are responsible for an array of functions like intracellular transportation, cell division and organization of structures and organelles within cells.

In normal circumstances, normal functioning of tau protein and microtubule regulation takes place and the proliferation and replacement of worn out neural cells with new ones is carried out.

When the normal functioning of tau protein is disrupted, the neural transportation is severely disturbed and leads to the buildup of neurofibrillary tangles and other neuro-toxic substances in the brain. These neurofibrillary tangles, essentially the aggregates of increasingly phosphorylated tau protein, are insoluble in nature and qualify as a prime marker molecule of Alzheimer’s disease diagnosis.

What Is Next In Alzheimer’s Disease Treatment?

In a press release, Dr Eric Kandel, MD Nobel Laureate and Kavli Professor of Brian Science at Columbia University said, “This study clearly shows that tau pathology, beginning in the entorhinal cortex, can lead to deficits in grid cell firing and underlies the deterioration of spatial cognition that we see in human Alzheimer’s disease”.

He further added that this was a significant advancement in understanding early progression of Alzheimer’s disease.

Researchers are excited about the findings in this study and are hopeful that it will help them learn more about the neuro-pathology of Alzheimer’s disease. Not only will this finding help in diagnosing the onset of Alzheimer’s disease earlier than before, it will also help in the formulation of targeted therapeutics with improved drug efficacy.

Leave A Reply

Your email address will not be published.