Parkinson's Disease vs ALS: Key Differences and Similarities

The number of patients affected by neurodegenerative diseases is increasing globally. With that in mind, it is important to understand the similarities and differences between the diseases. In this blog, we will compare two neurodegenerative diseases affecting the motor function - Parkinson’s disease and Amyotrophic Lateral Sclerosis. We will delve into their symptoms, pathology, genetics, prevalence and the possible treatment for these devastating diseases.
Frederika Malichová

Frederika Malichová

Neuroscientist at the University Of Cambridge.

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What Is The Difference Between Parkinson’s Disease and Amyotrophic Lateral Sclerosis?

The key difference between ALS and Parkinson's lies in the neurons they affect and the symptoms they cause. ALS affects motor neurons, while Parkinson's affects dopaminergic neurons in the basal ganglia. ALS causes muscle weakness and paralysis, while Parkinson's causes tremors and rigidity.

Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease or Motor Neurone Disease, is a progressive, fatal, neurodegenerative disorder that primarily affects the motor neurons in the brain and spinal cord. 
The disease is characterized by the degeneration of motor neurons, leading to muscle weakness and atrophy. The disease usually strikes between the ages of 40 and 60, and it affects more men than women. 
Symptoms of ALS impact motor functions and can include difficulty walking or running, trouble writing, and speech problems. 

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Interestingly, in sporadic cases of ALS, men are more likely to have a spinal onset of ALS, beginning with the symptoms in the muscles of the limbs [1, 2]. 
Women on the other hand, are more likely to have a bulbar onset of ALS, starting with difficulties in controlling the face, head, and neck muscles [2].
As the disease progresses, patients may lose their strength and ability to move. When muscles in the chest fail, respiratory failure can occur, which is often the cause of death in ALS patients. There is currently no cure for ALS, and the cause of the disease is not fully understood [3].  

Parkinson's Disease

Parkinson's Disease (PD), on the other hand, is a neurodegenerative disorder that primarily affects dopaminergic neurons in the brain. 
A notable feature of PD is the accumulation of a protein called α-synuclein into build-ups known as Lewy bodies in the neurons. 
Symptoms of PD also affect motor functions and can include tremors, bradykinesia (slowness of movement), rigidity, and balance problems. 
Interestingly, as with ALS, we observe differences in the disease among sexes. Men are about 1.5 to 2 times more likely to develop PD than women [4].
As with ALS, the cause of PD is not fully understood, and there is currently no cure. However, fortunately, there are treatments available that can help manage the symptoms of the disease [5]
While both ALS and PD are neurodegenerative diseases, they affect different types of neurons and result in distinct sets of symptoms. Both diseases are primarily sporadic, meaning they occur in people with no apparent family history of the disease. 
However, in some cases, they can be traced to specific genetic mutations. Despite the differences, both diseases involve the accumulation of abnormal protein aggregates in neurons, suggesting that common mechanisms may be at work. 

Symptoms: ALS vs Parkinson's Disease

What Are The Symptoms of ALS?

The early symptoms of ALS include difficulties in chewing and swallowing, muscle cramps, twitching particularly in the limbs, muscle weakness, slurred speech, and stiff muscles.

As the disease progresses, individuals have difficulties with motor functions. They become unable to walk and stand on their own, or use their arms and hands efficiently. Swallowing and speaking become more difficult, and breathing becomes problematic. Many people with ALS require a ventilator to survive [1, 3].

Unfortunately, most ALS patients die within 3~5 years of disease onset due to respiratory failure. However, in rare cases, patients may live longer. The famous physicist Stephen Hawking had slow-progressing ALS for over 50 years, and died at the age of 76.

In some cases, due to the link between frontotemporal dementia (FTD) and ALS, patients may also manifest frontal behavior symptoms and cognitive decline, including impairment in facial emotion recognition [6]

What Are The Symptoms of Parkinson's Disease?

Parkinson's disease also results in affecting both motor and non-motor brain functions. The motor symptoms of PD include resting tremor, cogwheel rigidity, extreme slowness of movement, shuffling gait, impaired balance, and akinesia. Swallowing and speaking difficulties are also common in Parkinson's disease.

Non-motor symptoms, which are quite common in PD, include depression, hallucinations, and sleep disturbances that seriously affect quality of life [6]

In comparison, while both diseases affect movement and can lead to difficulties with walking, chewing, swallowing, speaking, and breathing, PD is more likely to cause a broader range of symptoms.

In addition to movement, PD impairs memory, concentration, and decision-making. It can also cause mood swings, personality changes, and depression. Cognitive and psychiatric symptoms can also occur with ALS, but they are less common than in Parkinson's and appear in later stages of the disease.

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Causes: ALS vs Parkinson's Disease

What Causes ALS?

The exact cause of ALS is unknown, but it is divided into two categories: familial ALS (fALS) and sporadic ALS (sALS). Sporadic ALS, which accounts for 90-95% of cases, is thought to be due to environmental factors, although the specifics are not well understood[3, 7].

However, certain risk factors have been identified. Interestingly, it seems that athletes have a higher risk of developing ALS. A retrospective study of professional athletes in the National Football League in the United States found a 40-fold higher prevalence of ALS in comparison to the general US population [8].

Similarly, a study analysing cross-country skiers in Sweden determined a higher risk of ALS among long-distance cross-country skiers. Interestingly recreational skiers showed a largely reduced risk of ALS [9].

Further, a study found significant associations between ALS and exposure to certain pesticides like 2,4-D, glyphosate, carbaryl, and chlorpyrifos, suggesting the exposure to those is a risk factor for ALS [10].

Familial ALS: Can ALS Be Inherited?

ALS can be genetically inherited. Familial ALS, which accounts for 5-10% of cases, is due to gene mutations, with the most common causes associated with mutations in SOD1, TARDBP, FUS, and C9orf72 genes. 

Mutations in the C9orf72 gene have also been found to play an important role in cases of familial Frontotemporal Dementia [11]

What Causes Parkinson's Disease?

From Genome-Wide Association Studies, several genes have been proposed to be associated with PD.  Genes such as SNCA, LRRK2 VPS35, Parkin, PINK1, and DJ-1 were linked to both autosomal dominant or recessive forms of PD [12].

Other factors contributing to a higher probability of getting PD include increasing age, male sex, and pesticide exposure [13]. Interestingly, cigarette smoking and caffeine consumption are inversely associated with PD. 

To expand upon this, components in coffee such as caffeic acid and cholinergic acid seem to be showing neuroprotective properties in mice models of PD [14]

Although cigarette smoking has been associated with a decreased risk of PD, studies suggested that it either might have been only a result of future PD patients’ dislike of engagement in habitual activities [15], or alternatively, that nicotine may increase dopamine levels in the synaptic gap and thus contribute to the inverse association with PD [16]

Some studies suggest that genetic factors and exposure to certain environmental triggers, such as the neurotoxin β-methylamino-L-alanine, which can be found in cyanobacterial blooms in various waterbodies used also for agriculture, or sea food may play a role in the development of PD [17, 18].
In both ALS and PD, there is evidence suggesting that genetic susceptibility and environmental influences contribute to the development of these diseases. However, more research is needed to fully understand the causes and mechanisms of these complex diseases.

Prevalence: ALS vs Parkinson's Disease

What is the Prevalence of ALS?

According to a 2023 report, the prevalence of ALS in the United States is about 7.7 cases per 100,000 people [3]. However, other studies have reported different prevalence rates. The National ALS Registry in the United States reported a prevalence rate of 5.0 per 100,000 [19], and a study in Israel reported a prevalence of 8.1 per 100,000 population in 2013 [20]

What is the Prevalence of Parkinson's Disease?

The prevalence of Parkinson's disease is age-dependent. A systematic analysis from a study in 2016 detected 6.1 million of patients with PD, which went up from 2.5 million in 1990 [21]. However, the proportion of people affected by the disease can vary from region to region.

In conclusion, both ALS and Parkinson's disease are prevalent neurodegenerative diseases, with Parkinson's disease generally having a higher prevalence, particularly among the elderly. However, the exact prevalence rates can vary depending on the population and the methodology of the studies.

ALS vs Parkinson's Pathology: What Are the Mechanisms Behind the Diseases?

ALS Pathology

The major pathological hallmark of ALS is the abnormal accumulation of protein inclusions containing TDP-43, FUS, or SOD1 protein. This accumulation leads to the gradual degeneration of motor neurons, resulting in muscle weakness, atrophy, and eventually, at end-stage respiratory failure.

In familial cases of ALS, there is a clear indication of genetic inheritance and its contribution to the disease pathology [1, 22]

The pathology of ALS also involves a prion-like mechanism, where insoluble fibrillar aggregates of SOD1, TDP-43, and FUS proteins can act as seeds to trigger the aggregation of native counterparts, leading to a self-propagation mechanism similar to prion replication and spreading [22].

Interestingly, in a relatively recent development, researchers have proposed a link between the pathogenesis of ALS and the gut microbiome. We explored the evidence behind this fascinating connection in an earlier blog post.

Parkinson's Disease Pathology

Parkinson's is often associated with the presence of intraneuronal inclusions known as Lewy bodies, which are primarily composed of the protein α-synuclein. α-synuclein is involved in vesicle trafficking and contributes to proper synaptic functioning [23]

In PD, the pathology involves the misfolding and aggregation of the protein forming Lewy bodies. This process is thought to be a major contributor to the disease's onset and progression [24]

PD and ALS share some common features, including the presence of proteinaceous inclusions and the involvement of the dopamine system.

While both ALS and PD are neurodegenerative diseases characterized by the presence of protein inclusions, they affect different classes of neurons and involve different proteins and mechanisms.

ALS vs Parkinson's Treatment: What Are the Possible Treatments? 

Neurodegenerative diseases often present challenges in treatment. In some cases, we are fortunate to have available treatments, while in others, effective treatment remains an aspiration.
Currently, there is no cure for ALS. Therefore the treatment revolves around managing symptoms and improving the quality of life of the patients suffering from the disease. Such include physical therapies which are aimed to improve the mobility of the patients boosting flexibility, strength and independence.
Therapeutics such as Riluzole or Endaravone are approved treatments for ALS to lower the degree of damage to motor neurons. Last year (2023) a new drug – Tofersen – was approved, providing hope for ALS patients with a mutation on the SOD1 gene [25]
Excitingly, clinical trials using STEM-cell approaches are investigated to serve as a potential help to these patients [26]
However, with PD the treatment story is much different. As we explored in our separate blog about Parkinson’s disease, there are several treatments available for PD. These include therapeutical interventions as well as neurological surgeries.
Pharmaceutical treatments include dopamine precursor L-DOPA, monoamine oxidase type B (MAOB) inhibitors, Catecgol-O-methyltransferase (COMT) inhibitors and dopamine agonists [27].
Non-pharmaceutical treatments include deep brain stimulation, in which the patients get electrodes implanted into the subcortical structures of the brain.
Recently spinal cord implants were reported to improve the movement functioning of patients with PD which can serve as a novel non-pharmaceutical treatment [28]

Frederika Malichová

Frederika Malichová

Frederika is a postgraduate researcher at the University of Cambridge, where she investigates new biomarkers for Frontotemporal Dementia and other tauopathies. Her research has been published at prestigious conferences such as the Alzheimer’s Association International Conference 2023. She obtained her BSc in Biomedical Sciences from UCL, where she worked closely with the UK Dementia Research Institute.