A report on Parkinson's disease

Illustration of Parkinson's disease by William Richard Gowers, first published in A Manual of Diseases of the Nervous System (1886)
A man with PD displaying a flexed walking posture pictured in 1892
Handwriting of a person affected by PD
Parkin crystal structure
A Lewy body (stained brown) in a brain cell of the substantia nigra in Parkinson's disease: The brown colour is positive immunohistochemistry staining for alpha-synuclein.
An illustration of the dopamine pathways throughout the brain.
"Hot Cross Bun" sign that is commonly found in MRI of Multiple System Atrophy.
Pharmacological treatment of Parkinson's disease
COMT metabolizes levodopa to 3-O-methyldopa. COMT inhibitors help stop this reaction, allowing for more levodopa to cross the blood-brain barrier and become dopamine where it is needed.
Placement of an electrode into the brain: The head is stabilised in a frame for stereotactic surgery.
Deaths from PD per million persons in 2012
Jean-Martin Charcot, who made important contributions to the understanding of the disease and proposed its current name honoring James Parkinson
"Parkinson's awareness" logo with red tulip symbol
Muhammad Ali at the World Economic Forum in Davos, at the age of 64. He had shown signs of parkinsonism from the age of 38 until his death.

Long-term degenerative disorder of the central nervous system that mainly affects the motor system.

- Parkinson's disease
Illustration of Parkinson's disease by William Richard Gowers, first published in A Manual of Diseases of the Nervous System (1886)

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Skeletal formula of dopamine

Dopamine

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Neuromodulatory molecule that plays several important roles in cells.

Neuromodulatory molecule that plays several important roles in cells.

Skeletal formula of dopamine
Dopamine processing in a synapse. After release dopamine can either be taken up again by the presynaptic terminal, or broken down by enzymes.
TH: tyrosine hydroxylase
DOPA: L-DOPA
DAT: dopamine transporter
DDC: DOPA decarboxylase
VMAT: vesicular monoamine transporter 2
MAO: Monoamine oxidase
COMT: Catechol-O-methyl transferase
HVA: Homovanillic acid
Major dopamine pathways. As part of the reward pathway, dopamine is manufactured in nerve cell bodies located within the ventral tegmental area (VTA) and is released in the nucleus accumbens and the prefrontal cortex. The motor functions of dopamine are linked to a separate pathway, with cell bodies in the substantia nigra that manufacture and release dopamine into the dorsal striatum.
Main circuits of the basal ganglia. The dopaminergic pathway from the substantia nigra pars compacta to the striatum is shown in light blue.
Illustration of dopaminergic reward structures
Dopamine HCl preparation, single dose vial for intravenous administration
Cocaine increases dopamine levels by blocking dopamine transporters (DAT), which transport dopamine back into a synaptic terminal after it has been emitted.
Methamphetamine hydrochloride also known as crystal meth
Dopamine can be found in the peel and fruit pulp of bananas.

Parkinson's disease, a degenerative condition causing tremor and motor impairment, is caused by a loss of dopamine-secreting neurons in an area of the midbrain called the substantia nigra.

Normal brain on left contrasted with structural changes shown in brain on right of person with Alzheimer's disease, the most common neurodegenerative disease.

Neurodegenerative disease

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Caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration.

Caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration.

Normal brain on left contrasted with structural changes shown in brain on right of person with Alzheimer's disease, the most common neurodegenerative disease.
Comparison of brain tissue between healthy individual and Alzheimer's disease patient, demonstrating extent of neuronal death

Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple system atrophy, and prion diseases.

Image of a man diagnosed with dementia in the 1800s

Dementia

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Disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease.

Disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease.

Image of a man diagnosed with dementia in the 1800s
Image of a man diagnosed with dementia in the 1800s
A drawing of a woman diagnosed with dementia
A drawing of an old man diagnosed with senile dementia
Brain atrophy in severe Alzheimer's
Donepezil
Deaths per million persons in 2012 due to dementia
Disability-adjusted life year for Alzheimer and other dementias per 100,000 inhabitants in 2004.
Woman with dementia being cared for at home in Ethiopia

Causative subtypes of dementia may be based on a known disorder, such as Parkinson's disease, for Parkinson's disease dementia; Huntington's disease, for Huntington's disease dementia; vascular disease, for vascular dementia–as vascular brain injury, including stroke, often results in vascular dementia; or many other medical conditions, including HIV infection, causing HIV dementia; and prion diseases.

Skeletal formula of L -DOPA

L-DOPA

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Amino acid that is made and used as part of the normal biology of some plants and animals, including humans.

Amino acid that is made and used as part of the normal biology of some plants and animals, including humans.

Skeletal formula of L -DOPA

As a drug, it is used in the clinical treatment of Parkinson's disease and dopamine-responsive dystonia.

Microscopic image of a Lewy body (arrowhead) in a neuron of the substantia nigra; scale bar=20 microns (0.02mm)

Dementia with Lewy bodies

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Type of dementia characterized by changes in sleep, behavior, cognition, movement, and regulation of automatic bodily functions.

Type of dementia characterized by changes in sleep, behavior, cognition, movement, and regulation of automatic bodily functions.

Microscopic image of a Lewy body (arrowhead) in a neuron of the substantia nigra; scale bar=20 microns (0.02mm)
People with DLB are very sensitive to antipsychotic medications like haloperidol, which carry an increased risk of morbidity and mortality in DLB.
A ribbon diagram of apolipoprotein E. Variants of this protein influence the risk of developing DLB.
This photomicrograph shows brown-immunostained alpha-synuclein in Lewy bodies (large clumps) and Lewy neurites (thread-like structures) in the neocortical tissue of a person who died with Lewy body disease.
Positron emission tomography, for example, using PiB is helpful in the diagnosis of DLB.
Adult connected to wires from sensors for polysomnography
According to his widow, Robin Williams (pictured in 2011) was diagnosed during autopsy as having diffuse Lewy bodies.

The synucleinopathies include Parkinson's disease, multiple system atrophy, and other rarer conditions.

Drawing comparing a normal aged brain (left) and the brain of a person with Alzheimer's. Characteristics that separate the two are pointed out.

Alzheimer's disease

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Neurodegenerative disease that usually starts slowly and progressively worsens.

Neurodegenerative disease that usually starts slowly and progressively worsens.

Drawing comparing a normal aged brain (left) and the brain of a person with Alzheimer's. Characteristics that separate the two are pointed out.
Stages of atrophy in Alzheimer's.
A normal brain on the left and a late-stage Alzheimer's brain on the right
In Alzheimer's disease, changes in tau protein lead to the disintegration of microtubules in brain cells.
Histopathologic images of Alzheimer's disease, in the CA3 area of the hippocampus, showing an amyloid plaque (top right), neurofibrillary tangles (bottom left), and granulovacuolar degeneration bodies (bottom center)
PET scan of the brain of a person with Alzheimer's disease showing a loss of function in the temporal lobe
Cognitive tests such as the Mini–Mental State Examination (MMSE) can help in the diagnosis of Alzheimer's disease. In this test instructions are given to copy drawings like the one shown, remember some words, read, and subtract numbers serially.
Intellectual activities such as playing chess or regular social interaction have been linked to a reduced risk of Alzheimer's disease in epidemiological studies, although no causal relationship has been found.
Three-dimensional molecular model of donepezil, an acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease symptoms
Molecular structure of memantine, a medication approved for advanced Alzheimer's disease symptoms
Alois Alzheimer's patient Auguste Deter in 1902. Hers was the first described case of what became known as Alzheimer's disease.
Self-portrait of artist William Utermohlen, created after Alzheimer's disease diagnosis

Excitotoxicity occurs not only in Alzheimer's disease, but also in other neurological diseases such as Parkinson's disease and multiple sclerosis.

Substantia nigra highlighted in red.

Substantia nigra

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Basal ganglia structure located in the midbrain that plays an important role in reward and movement.

Basal ganglia structure located in the midbrain that plays an important role in reward and movement.

Substantia nigra highlighted in red.
Coronal slices of human brain showing the basal ganglia, globus pallidus: external segment (GPe), subthalamic nucleus (STN), globus pallidus: internal segment (GPi), and substantia nigra (SN, red). The right section is the deeper one, closer to the back of the head
Diagram of the main components of the basal ganglia and their interconnections
Anatomical overview of the main circuits of the basal ganglia, substantia nigra is shown in black. Picture shows 2 coronal slices that have been superimposed to include the involved basal ganglia structures. + and – signs at the point of the arrows indicate respectively whether the pathway is excitatory or inhibitory in effect. refer to excitatory glutamatergic pathways, refer to inhibitory GABAergic pathways and  refer to dopaminergic pathways that are excitatory on the direct pathway and inhibitory on the indirect pathway.
Substantia nigra with loss of cells and Lewy body pathology
Dopamine and serotonin
Degradation of substantia nigra associated with Parkinson's disease.
Horizontal MRI (T1 weighted) slice with highlighting indicating location of the substantia nigra.
Enhanced Neuromelanin MRI with Color images (RGB) showing Substantia nigra pars compacta
Microfilming

Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta.

The skeletal structure of dopamine

Dopamine agonist

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Compound that activates dopamine receptors.

Compound that activates dopamine receptors.

The skeletal structure of dopamine
Bromocriptine
Apomorphine
Rotigotine

Dopamine agonists are used in Parkinson’s disease and, to a lesser extent, to treat depression, hyperprolactinemia and restless legs syndrome.

Photomicrographs of regions of substantia nigra in this Parkinson's patient show Lewy bodies and Lewy neurites in various magnifications. Top panels show a 60× magnification of the alpha-synuclein intraneuronal inclusions aggregated to form Lewy bodies. The bottom panels are 20× magnification images that show strand-like Lewy neurites and rounded Lewy bodies of various sizes. Neuromelanin-laden cells of the substantia nigra are visible in the background. Stains used: mouse monoclonal alpha-synuclein antibody; counterstained with Mayer's haematoxylin

Lewy body

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Photomicrographs of regions of substantia nigra in this Parkinson's patient show Lewy bodies and Lewy neurites in various magnifications. Top panels show a 60× magnification of the alpha-synuclein intraneuronal inclusions aggregated to form Lewy bodies. The bottom panels are 20× magnification images that show strand-like Lewy neurites and rounded Lewy bodies of various sizes. Neuromelanin-laden cells of the substantia nigra are visible in the background. Stains used: mouse monoclonal alpha-synuclein antibody; counterstained with Mayer's haematoxylin
Lewy bodies
Photomicrograph of the dorsal motor nucleus of the vagus nerve (DmX) in a transverse section along the upper medulla shown to be affected by the abnormally deposited alpha synuclein as part of intraneuronal Lewy bodies found (extreme right)
Lewy neurites in a DLB case. Stain application: immunohistochemical

Lewy bodies are the inclusion bodies – abnormal aggregations of protein – that develop inside nerve cells affected by Parkinson's disease (PD), the Lewy body dementias (Parkinson's disease dementia and dementia with Lewy bodies (DLB)), and some other disorders.

An edited microscopic image of a medium spiny neuron (yellow) with an inclusion body (orange), which occurs as part of the disease process (image width 360 µm)

Huntington's disease

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Neurodegenerative disease that is mostly inherited.

Neurodegenerative disease that is mostly inherited.

An edited microscopic image of a medium spiny neuron (yellow) with an inclusion body (orange), which occurs as part of the disease process (image width 360 µm)
Graphic showing at top normal range of repeats, and disease-causing range of repeats.
Huntington's disease is inherited in an autosomal dominant fashion. The probability of each offspring inheriting an affected gene is 50%. Inheritance is independent of sex, and the phenotype does not skip generations.
A microscope image of a neuron with an inclusion body (stained orange) caused by HD, image width 250 µm
The area of the brain most damaged in early Huntington's disease is the dorsal striatum made up of the caudate nucleus and the putamen.
Coronal section from an MR brain scan of a patient with HD, showing atrophy of the heads of the caudate nuclei, enlargement of the frontal horns of the lateral ventricles (hydrocephalus ex vacuo), and generalized cortical atrophy
Chemical structure of tetrabenazine, an approved compound for the management of chorea in HD
In 1872, George Huntington described the disorder in his first paper "On Chorea" at the age of 22.
The death of Woody Guthrie led to the foundation of the Committee to Combat Huntington's Disease

About eight percent of cases start before the age of 20 years, and are known as juvenile HD, which typically present with the slow movement symptoms of Parkinson's disease rather than those of chorea.