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).
Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by tremors, slow movement, muscle rigidity, and postural instability, autonomic dysfunction 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.
Progressive supranuclear palsy (PSP) is a late-onset neurodegenerative disease involving the gradual deterioration and death of specific volumes of the brain. The condition leads to symptoms including loss of balance, slowing of movement, difficulty moving the eyes, and cognitive impairment. PSP may be mistaken for other types of neurodegeneration such as Parkinson's disease, frontotemporal dementia and Alzheimer's disease. The cause of the condition is uncertain, but involves the accumulation of tau protein within the brain. Medications such as levodopa and amantadine may be useful in some cases.
Neuropathology is the study of disease of nervous system tissue, usually in the form of either small surgical biopsies or whole-body autopsies. Neuropathologists usually work in a department of anatomic pathology, but work closely with the clinical disciplines of neurology, and neurosurgery, which often depend on neuropathology for a diagnosis. Neuropathology also relates to forensic pathology because brain disease or brain injury can be related to cause of death. Neuropathology should not be confused with neuropathy, which refers to disorders of the nerves themselves rather than the tissues. In neuropathology, the branches of the specializations of nervous system as well as the tissues come together into one field of study.
Amyloid plaques are extracellular deposits of the amyloid beta (Aβ) protein mainly in the grey matter of the brain. Degenerative neuronal elements and an abundance of microglia and astrocytes can be associated with amyloid plaques. Some plaques occur in the brain as a result of aging, but large numbers of plaques and neurofibrillary tangles are characteristic features of Alzheimer's disease. The plaques are highly variable in shape and size; in tissue sections immunostained for Aβ, they comprise a log-normal size distribution curve, with an average plaque area of 400-450 square micrometers (μm2). The smallest plaques, which often consist of diffuse deposits of Aβ, are particularly numerous. Plaques form when Aβ misfolds and aggregates into oligomers and longer polymers, the latter of which are characteristic of amyloid.
Neurofibrillary tangles (NFTs) are intracellular aggregates of hyperphosphorylated tau protein that are most commonly known as a primary biomarker of Alzheimer's disease. Their presence is also found in numerous other diseases known as tauopathies. Little is known about their exact relationship to the different pathologies.
Tauopathies are a class of neurodegenerative diseases characterized by the aggregation of abnormal tau protein. Hyperphosphorylation of tau proteins causes them to dissociate from microtubules and form insoluble aggregates called neurofibrillary tangles. Various neuropathologic phenotypes have been described based on the anatomical regions and cell types involved as well as the unique tau isoforms making up these deposits. The designation 'primary tauopathy' is assigned to disorders where the predominant feature is the deposition of tau protein. Alternatively, diseases exhibiting tau pathologies attributed to different and varied underlying causes are termed 'secondary tauopathies'. Some neuropathologic phenotypes involving tau protein is Alzheimer's disease, Pick disease, Progressive supranuclear palsy, and corticobasal degeneration.
In medicine, proteinopathy, or proteopathy, protein conformational disorder, or protein misfolding disease, is a class of diseases in which certain proteins become structurally abnormal, and thereby disrupt the function of cells, tissues and organs of the body. Often the proteins fail to fold into their normal configuration; in this misfolded state, the proteins can become toxic in some way or they can lose their normal function. The proteinopathies include such diseases as Creutzfeldt–Jakob disease and other prion diseases, Alzheimer's disease, Parkinson's disease, amyloidosis, multiple system atrophy, and a wide range of other disorders. The term proteopathy was first proposed in 2000 by Lary Walker and Harry LeVine.
The applause sign is a behavioural indicator, relevant to neurodegenerative conditions, characterised by a patient’s inability to execute the same number of hand claps as demonstrated by an examiner.
In the human brain, the nucleus basalis, also known as the nucleus basalis of Meynert or nucleus basalis magnocellularis, is a group of neurons located mainly in the substantia innominata of the basal forebrain. Most neurons of the nucleus basalis are rich in the neurotransmitter acetylcholine, and they have widespread projections to the neocortex and other brain structures.
Braak staging refers to two methods used to classify the degree of pathology in Parkinson's disease and Alzheimer's disease. These methods are used both in research and for the clinical diagnosis of these diseases and are obtained by performing an autopsy of the brain.
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.
Parkinson's disease (PD) is a complicated neurodegenerative disease that progresses over time and is marked by bradykinesia, tremor, and stiffness. As the condition worsens, some patients may also experience postural instability. Parkinson's disease (PD) is primarily caused by the gradual degeneration of dopaminergic neurons in the region known as the substantia nigra along with other monoaminergic cell groups throughout the brainstem, increased activation of microglia, and the build-up of Lewy bodies and Lewy neurites, which are proteins found in surviving dopaminergic neurons.
Florbetaben, sold under the brand name Neuraceq, is a diagnostic radiotracer developed for routine clinical application to visualize β-amyloid plaques in the brain. It is a fluorine-18 (18F)-labeled stilbene derivative.
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).
Primary age-related tauopathy (PART) is a neuropathological designation introduced in 2014 to describe the neurofibrillary tangles (NFT) that are commonly observed in the brains of normally aged and cognitively impaired individuals that can occur independently of the amyloid plaques of Alzheimer's disease (AD). The term and diagnostic criteria for PART were developed by a large group of neuropathologists, spearheaded by Drs. John F. Crary and Peter T. Nelson. Despite some controversy, the term PART has been widely adopted, with the consensus criteria cited over 1130 times as of April 2023 according to Google Scholar.
LATE is a term that describes a prevalent condition with impaired memory and thinking in advanced age, often culminating in the dementia clinical syndrome. In other words, the symptoms of LATE are similar to those of Alzheimer's disease.
Eva Braak (1939-2000) was a German anatomist, mostly known for the Braak and Braak Alzheimer disease stages. She was professor at the Institute of Clinical Neuroanatomy, Johann Wolfgang Goethe-University, Frankfurt am Main.
Granulovacuolar degeneration refers to the occurrence within neurons of abnormal, fluid-filled bubbles (vacuoles) containing a dense proteinaceous granule. Granulovacuoles occur most commonly in pyramidal neurons of the hippocampus. They are present in small numbers in non-demented elderly people, but increase in frequency in Alzheimer's disease and other tauopathies. In Alzheimer's disease, granulovacuoles proliferate stage-wise in different brain areas, and their prevalence is correlated with the degree of tauopathy, Abeta plaque pathology, and cerebral amyloid angiopathy. Immunohistochemical analyses have found that the inner granule includes several proteins, including tubulin tau protein, TDP-43 and others. Although granulovacuoles and their functional significance are still poorly understood, they have been compared to autophagic vacuoles
Margaret Ransone Murray was an American scientist known primarily for her work on methods to establish cultures of neuronal cells. Her in vitro studies in cellular neurobiology shed light on both nerve- muscle relationships and axon myelination.
