Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia, rigidity, and postural instability. These are the four motor symptoms found in Parkinson's disease (PD) – after which it is named – dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), and many other conditions. This set of symptoms occurs in a wide range of conditions and may have many causes, including neurodegenerative conditions, drugs, toxins, metabolic diseases, and neurological conditions other than PD.
Dementia with Lewy bodies (DLB) is a type of dementia characterized by changes in sleep, behavior, cognition, movement, and regulation of automatic bodily functions. Memory loss is not always an early symptom. The disease worsens over time and is usually diagnosed when cognitive impairment interferes with normal daily functioning. Together with Parkinson's disease dementia, DLB is one of the two Lewy body dementias. It is a common form of dementia, but the prevalence is not known accurately and many diagnoses are missed. The disease was first described by Kenji Kosaka in 1976.
Lewy body dementias are two similar and common subtypes of dementia: Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). Both are characterized by changes in thinking, movement, behavior, and mood. The two conditions have similar features and may have similar causes, and are believed to belong on a spectrum of Lewy body disease that includes Parkinson's disease. As of 2014, they were more often misdiagnosed than any other common dementia.
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, and some other disorders. They are also seen in cases of multiple system atrophy, particularly the parkinsonian variant (MSA-P).
Alpha-synuclein(aSyn) is a protein that, in humans, is encoded by the SNCA gene. Alpha-synuclein is a neuronal protein that regulates synaptic vesicle trafficking and subsequent neurotransmitter release.
Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by autonomic dysfunction, tremors, slow movement, muscle rigidity, and postural instability and ataxia. This is caused by progressive degeneration of neurons in several parts of the brain including the basal ganglia, inferior olivary nucleus, and cerebellum.
Tauopathy belongs to a class of neurodegenerative diseases involving the aggregation of tau protein into neurofibrillary or gliofibrillary tangles in the human brain. Tangles are formed by hyperphosphorylation of the microtubule protein known as tau, causing the protein to dissociate from microtubules and form insoluble aggregates. The mechanism of tangle formation is not well understood, and whether tangles are a primary cause of Alzheimer's disease or play a peripheral role is unknown.
A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple system atrophy, tauopathies, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well.
Beta-synuclein is a protein that in humans is encoded by the SNCB gene.
Leucine-rich repeat kinase 2 (LRRK2), also known as dardarin and PARK8, is a large, multifunctional kinase enzyme that in humans is encoded by the LRRK2 gene. LRRK2 is a member of the leucine-rich repeat kinase family. Variants of this gene are associated with an increased risk of Parkinson's disease and Crohn's disease.
Neurogenetics studies the role of genetics in the development and function of the nervous system. It considers neural characteristics as phenotypes, and is mainly based on the observation that the nervous systems of individuals, even of those belonging to the same species, may not be identical. As the name implies, it draws aspects from both the studies of neuroscience and genetics, focusing in particular how the genetic code an organism carries affects its expressed traits. Mutations in this genetic sequence can have a wide range of effects on the quality of life of the individual. Neurological diseases, behavior and personality are all studied in the context of neurogenetics. The field of neurogenetics emerged in the mid to late 20th century with advances closely following advancements made in available technology. Currently, neurogenetics is the center of much research utilizing cutting edge techniques.
Alzheimer's Disease Neuroimaging Initiative (ADNI) is a multisite study that aims to improve clinical trials for the prevention and treatment of Alzheimer's disease (AD). This cooperative study combines expertise and funding from the private and public sector to study subjects with AD, as well as those who may develop AD and controls with no signs of cognitive impairment. Researchers at 63 sites in the US and Canada track the progression of AD in the human brain with neuroimaging, biochemical, and genetic biological markers. This knowledge helps to find better clinical trials for the prevention and treatment of AD. ADNI has made a global impact, firstly by developing a set of standardized protocols to allow the comparison of results from multiple centers, and secondly by its data-sharing policy which makes available all at the data without embargo to qualified researchers worldwide. To date, over 1000 scientific publications have used ADNI data. A number of other initiatives related to AD and other diseases have been designed and implemented using ADNI as a model. ADNI has been running since 2004 and is currently funded until 2021.
The history of Parkinson's disease expands from 1817, when British apothecary James Parkinson published An Essay on the Shaking Palsy, to modern times. Before Parkinson's descriptions, others had already described features of the disease that would bear his name, while the 20th century greatly improved knowledge of the disease and its treatments. PD was then known as paralysis agitans. The term "Parkinson's disease" was coined in 1865 by William Sanders and later popularized by French neurologist Jean-Martin Charcot. Paralysis
Parkinson's disease (PD) is a degenerative disorder of the central nervous system. Most people with PD have idiopathic Parkinson's disease. A small proportion of cases, however, can be attributed to known genetic factors. Other factors such as environmental toxins, herbicides, pesticides, and fungicides, have been associated with the risk of developing PD, but no causal relationships have been proven.
Alice M. Lazzarini is a scientist, author and researcher on neurogenetic disorders, including Huntington's disease and Parkinson's disease. She is an assistant professor of Neurology at Rutgers Robert Wood Johnson Medical School, where her work helped establish the genetic basis of Parkinson's. Later in life, she was diagnosed with Parkinson's—the very disease she had spent decades researching.
Synucleinopathies are neurodegenerative diseases characterised by the abnormal accumulation of aggregates of alpha-synuclein protein in neurons, nerve fibres or glial cells. There are three main types of synucleinopathy: Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Other rare disorders, such as various neuroaxonal dystrophies, also have α-synuclein pathologies. Additionally, autopsy studies have shown that around 6% of sporadic Alzheimer's Disease exhibit α-synuclein positive Lewy pathology, and are sub-classed as Alzheimer's Disease with Amygdalar Restricted Lewy Bodies (AD/ALB).
David Chaim Rubinsztein FRS FMedSci is the Deputy Director of the Cambridge Institute of Medical Research (CIMR), Professor of Molecular Neurogenetics at the University of Cambridge and a UK Dementia Research Institute Professor.
The neuroscience of aging is the study of the changes in the nervous system that occur with ageing. Aging is associated with many changes in the central nervous system, such as mild atrophy of the cortex that is considered non-pathological. Aging is also associated with many neurological and neurodegenerative disease such as amyotrophic lateral sclerosis, dementia, mild cognitive impairment, Parkinson's disease, and Creutzfeldt–Jakob disease.
Bryan J. Traynor is a neurologist and a senior investigator at the National Institute on Aging, and an adjunct professor at Johns Hopkins University. Dr. Traynor studies the genetics of human neurological conditions such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). He led the international consortium that identified pathogenic repeat expansions in the C9orf72 gene as a common cause of ALS and FTD. Dr. Traynor also led efforts that identified other Mendelian genes responsible for familial ALS and dementia, including VCP, MATR3, KIF5A, HTT, and SPTLC1.
Early-onset parkinsonism-intellectual disability syndrome is a very rare genetic disorder which is characterized by intellectual disabilities, psychomotor developmental delays, macrocephaly, and Parkinson's disease which starts before the age of 45. Additional symptoms include epilepsy, strabismus, and frontal bossing.
