Overview

A fatal, but rare neurodegenerative disease, Creutzfeldt-Jakob Disease (CJD) is a currently untreatable prion disease. When it comes to the brain, Creutzfeldt-Jakob Disease is the ultimate disrupter, turning healthy neurons into a chaotic tangle faster than you can say "protein misfolding." Affecting about 1 in every 100,000 people, it progresses quite swiftly ending with fatality for about 70% of the patients afflicted by it.¹ Although not as well-known as other neurodegenerative diseases, such as Alzheimer’s Disease or other forms of dementia, it still bears profound impacts on the individuals as well as on the families of those affected. 

What are prion diseases?

Prion diseases are caused due to issues in protein conformations. They are neither afflicted by a virus or a viroid but a separate structure known as a PRION. ‘Prion’ comes from the words ‘protein infection’. Different strains of prions cause varying diseases such as bovine spongiform encephalopathy (BSE, also referred to as “mad cow disease”), scrapie, and chronic wasting disease. Prions are cell surface proteins found within the neurotransmitters and receptors of the brain (and less commonly in the spleen) that exist in the form PrPc which does not cause disease. 

Figure 1. Brain tissue from a CJD patient under microscopic examination shows a high concentration of prion proteins that are responsible for progressive neurodegeneration.⁸

Prion diseases are a group of fatal and infectious neurodegenerative diseases affecting humans and diverse animal species.² The infectious nature of prion diseases first became evident more than 70 years ago when accidental transmission of scrapie occurred in sheep. In humans an infectious origin was suspected for kuru, a prion disease identified in some cannibalistic tribes of New Guinea.³

It shares the characteristics of late-age onset cognitive decline, accumulation of misfolded protein aggregates in the central nervous system, and neurodegeneration with a large group of disorders including Alzheimer’s and Parkinson’s diseases. Despite the similarities, prion disease is the only naturally occurring infectious protein misfolding disorder that can be transmitted within and, in rare occasions, between species.

How does CJD affect your brain?

Initially described by Hans Gerhard Creutzfeldt in 1920 and Alfons Maria Jakob in 1923; the term CJD was finally coined after Clearance J. Gibbs began using the term “Creutzfeldt-Jakob Disease” since the acronym CJD was similar to his initials.⁴

CJD mainly affects the central nervous system. The chief functional unit of the central nervous system is a neuron, which is a cell that can store, receive, and transmit information. Neurons are organised topographically and allow various body areas to function with accuracy, together making up the entirety of the brain. 

When somebody is afflicted with CJD, they develop spongy-like textures within the vacuoles of the brain. This can be seen in a piece of brain tissue from the frontal cortex of the brain when viewed under the microscope.⁶ This sponge-like texture is due to cell death caused by the accumulation of prions as a result of protein misfolding, leading to brain shrinkage. 

Figure 2. Pathological analysis of tissue specimens affected with CJD showing spongy-like appearance using Hematoxylin and Eosin stain.⁹

Changes in brain structure and function due to CJD

CJD mainly leads to involuntary muscle spasms within the body, thereby causing changes to the fronto-temporal lobes within the brain. At terminal stages, because of neuronal loss, it causes changes in the cerebellum, cortex, striatum, and thalamus, causing a reduction in grey matter.⁷ 

Figure 3. Labelled structure of the brain showing the major parts.¹⁰ 

The damage to the brain structure, mainly the frontal and temporal lobe (that control movement and emotions and memory respectively) causes memory impairment, behavioural changes, cognitive decline, impaired gait as some of the early symptoms. 

People affected by CJD also experience a condition that is opposite to hypochondria termed as anosognosia, which is when an individual does not have enough insight on their current medical condition and cannot comprehend a disease that is affecting them. 

Anosognosia tends to cause feelings of depression, anxiety, and mood swings. Either due to their own feelings or the emotional toll on the caretakers that eventually manifests onto the person, symptoms of paranoia, behaviour changes such as increase in depression and aggression, confusion may occur.

Other symptoms may present, such as:

• loss of coordination and balance (ataxia) 
• involuntary muscle spasms (myoclonus, or myoclonic jerks)
• dementia
• problems swallowing (dysphagia)
• difficulty speaking (aphasia) 
• blurry vision, possibly leading to blindness 
• loss of appetite

Clinical manifestations

The aforementioned symptoms - such as myoclonic jerks, advancing dementia, and cerebellar ataxia - are in line with the spongiform (sponge-like texture) changes that occur in the tissue of the brain and they also correlate with neuronal loss as a result of prion accumulation in the brain regions. Further, the symptoms can translate to visual disturbances and dysphagia which can be quite frustrating to experience for the sufferer. 

When the sufferer has difficulty swallowing or speaking due to dysphagia, it can be hard to consume food and lead to loss of appetite and weight. There can also be respiratory depression that leads to difficulty or shallow breathing, which may lead to the development of pneumonia when paired with anosognosia.

When grossly examined, advanced CJD can show marked atrophy in the cerebellum and cerebral cortex. 

FAQs

How does Creutzfeldt-Jakob disease affect the brain?

Being a neurodegenerative disease, Creutzfeldt-Jakob disease (CJD) is a rare disorder. Affecting only 1 in a 100,000 people, it tends to spread quite quickly once manifested. This happens due to the development of misfolded proteins as a result of changes in cellular homeostasis leading to the formation of prions that accumulate in the brain cells causing a decline in neurons.

CJD tends to affect various regions of the brain including the cerebellum, cerebral cortex, and basal ganglia. This mainly affects the part of the brain associated with movement, hence its characteristic symptom being involuntary muscle jerks. CJD also is followed by a series of other symptoms such as change in behaviour, loss in memory, progressive dementia, and impaired gait. Since it mainly affects the fronto-temporal lobe, the individual experiences difficulty swallowing and speaking, muscle twitches, and further confusion and loss of memory and appetite.

What are the involuntary movements involved in CJD?

Myoclonic jerks, colloquially termed as involuntary movement, are a principal feature of CJD. This is due to CJD primarily affecting the frontal lobe of the brain. Myoclonus refers to brief, sudden, involuntary movement in the muscles that affect various regions within the body. These jerky movements are usually spontaneous and irregular, and they can occur in the presence or absence of an external stimuli.

These muscle jerks can be severe or subtle and they may interfere with regular day-to-day activities. One of the earliest and most prominent symptoms of CJD is myoclonus followed by rapidly progressive dementia and other aforementioned symptoms.

What disease destroys brain cells?

Diseases that tend to negatively affect and destroy brain cells are termed as prion or neurodegenerative diseases. They cause a decline in one’s cognitive abilities as a result of neurological dysfunction because of neuronal loss. One of the most common brain cell-destroying diseases is Alzhiemer’s disease, characterised by the accumulation of protein aggregates to an abnormal degree. There are different proteins that accumulate for different diseases, such as beta-amyloid plaques for Alzheimer’s.

Parkinson's disease is another such example of a neurodegenerative disease that causes progressive loss of dopamine-producing neurons within the brain that causes cell death. This disease also causes the death of neurons followed by motor dysfunction and symptoms such as bradykinesia, rigidity, and tremors. 

Creutzfeldt-Jakob disease (CJD) is also one of the other examples of a disease that tends to destroy cells in the brain. In CJD, the abnormal aggregation of misfolded prion proteins in the tissue within the brain tends to cause widespread damage to the neurons, which then leads to rapidly progressive dementia amongst other neurological deficits.

How do prions cause brain damage?

Insoluble aggregates are formed due to the increased protein misfolding because of prions from increased disruption in cellular homeostasis. These aggregates then accumulate in the brain, causing brain cell death and the loss of neurons, which ultimately leads to progressive neurodegeneration and the onset of brain damage.

In the case of Creutzfeldt-Jakob disease (CJD) and other prion diseases, such as variant CJD and kuru, the abnormal prion protein (PrPSc) is believed to be the causative agent of brain damage. PrPSc is formed when the normal prion protein (PrPC) undergoes a conformational change and adopts an abnormal, infectious form. PrPSc can then induce the misfolding of other PrPC molecules, leading to the spread of pathological protein aggregates throughout the brain.

The accumulation of PrPSc in the brain tissue disrupts neuronal function, triggers neuroinflammation, and ultimately results in the death of brain cells. This widespread neuronal damage leads to the characteristic symptoms of prion diseases, including rapidly progressive dementia, involuntary movements, and other neurological deficits.

Summary 

CJD, often characterised by spongiform-like vacuoles being formed within the brain when examined via immunohistological laboratory techniques, is a progressive but rare neurodegenerative disorder. It is characterised by myoclonic movements, mainly due to prion formation in the brain affecting various regions, but rudimentarily the frontal and temporal lobe in the brain. It leads to a shrinkage of brain regions due to the accumulation of misfolded proteins and thereby reducing grey matter.