Neurodegenerative diseases: Amyotrophic lateral sclerosis, Multiple sclerosis, Parkinson, Alzheimer, Huntington

Neurodegenerative disease is an umbrella term for a range of conditions which primarily affect the neurons in the human brain. Neurodegenerative diseases represent a major threat to human health. These age-dependent disorders are becoming increasingly prevalent, in part because the elderly population has increased in recent years.

· Neurons are the building blocks of the nervous system which includes the brain and spinal cord. Neurons normally don’t reproduce or replace themselves, so when they become damaged or die they cannot be replaced by the body.

Neurodegenerative diseases are incurable and debilitating conditions that result in progressive degeneration and / or death of nerve cells. This causes problems with movement (called ataxias), mental functioning (called dementias) and affect a person's ability to move, speak and breathe. Neurodegenerative disorders impact many families - these disorders are not easy for the individual nor their loved ones.

Neurodegenerative diseases are basically caused by the death of cells in the brain.

In Alzheimer’s, this destruction primarily destroys memory.

In Parkinson’s and Huntington’s, it primarily affects movement.

Different proteins have been implicated in each of the three diseases: Alzheimer’s, Parkinson’s, and Huntington’s. In Alzheimer’s, it’s tau. In Parkinson’s, it’s alpha-synuclein. In Huntington’s, it’s huntingtin.

Molecular Abnormality

The most common neurodegenerative disorders are amyloidoses, tauopathies, α-synucleinopathies, and TDP-43 proteinopathies. The protein abnormalities in these disorders have abnormal conformational properties. Growing experimental evidence suggests that abnormal protein conformers may spread from cell to cell along anatomically connected pathways, which may in part explain the specific anatomical patterns observed at autopsy.

1. Amyloids are insoluble fibrous proteins that have specific structural characteristics, including a β-sheet-rich secondary structure. The protein abnormalities of almost all common neurodegenerative diseases have some characteristics of amyloid. In neurodegenerative diseases, amyloid-like filamentous aggregates are mostly within the cytoplasm of neurons and glia. Extracellular deposits of amyloid can be found in the brain parenchyma as plaques or in the walls of blood vessels as amyloid angiopathy. eg  Gerstmann–Sträussler–Scheinker disease (GSS) (A,B), Creutzfeldt–Jakob disease (CJD) (C,D), and Alzheimer’s disease are all Amyloidoses

2. Tauopathies: Tau is a type of protein that is part of the structural function of nerves, necessary for nerves to transmit impulses efficiently. Certain diseases can change normal tau into forms that disrupt nerve impulses, and this group of diseases are called tauopathies. Examples include Alzheimer's Disease, Parkinson's Disease and corticobasal degeneration. Many of these diseases develop in the later stages of life, although some develop in middle age or earlier. Tauopathies also include progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), argyrophilic grain disease (AGD) and frontotemporal dementia.

3. Synucleinopathies are a group of neurodegenerative disorders characterized by fibrillary aggregates of alpha-synuclein protein in the cytoplasm of selective populations of neurons and glia. These disorders include Parkinson's disease (PD), dementia with Lewy bodies (DLB), pure autonomic failure (PAF), and multiple system atrophy (MSA). Because of clinical overlap, differential diagnosis is sometimes very difficult. eg Parkinsonism is the predominant symptom of PD, but it can be indistinguishable from the parkinsonism of DLB and MSA. The deposition of aggregates of synuclein in neurons and glia suggests that a common pathogenic mechanism may exist for these disorders.

4. TDP-43 proteinopathies are a set of neurodegenerative disorders characterized pathologically by cytoplasmic inclusions composed of TDP-43. The pathology has been implicated in three major diseases

· Motor Neuron Disease (vast majority of cases)

· Frontotemporal lobar degeneration

· Limbic-predominant age-related TDP-43 encephalopathy (by definition; often diagnosed clinically as dementia of the Alzheimer type)

· Others neurodegenerative disorders are less well known to feature TDP-43 proteinopathy: Huntington disease; Parkinson disease and variants, eg Perry syndrome, postencephalitic parkinsonism 

5. Prion Diseases are asociated with the build up in the brain (and some other organs) of an abnormal or ‘rogue’ form of a naturally occurring cellular protein, known as the prion protein.

Amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) are both neurodegenerative diseases that affect the central nervous system (CNS). Each attacks different portions of the body’s nerves and affects muscle movements.

In a few ways, these two diseases are similar. However, their key differences determine a lot about their treatment and outlook:

Amyotrophic lateral sclerosis (ALS)	Multiple sclerosis (MS)
affects the motor neurons of the central nervous system (CNS), near the spinal cord	affects the brain and spinal cord
often leaves people paralyzed in its later stages	can affect mobility in its later stages, but rarely leaves people completely debilitated
causes more physical difficulties	causes more cognitive impairment
not proven to be an autoimmune disease	an immune-mediated disease
more common in men	more common in women
most commonly diagnosed between 40 to 70 years old	most commonly diagnosed between 20 to 50 years old
no known cure	no known cure
often debilitating and ultimately fatal	rarely debilitating or fatal