Pick's disease
Encyclopedia
Pick's disease, is a rare neurodegenerative disease that causes progressive destruction of nerve
cells in the brain
. Symptoms include loss of speech (aphasia
), and dementia. While some of the symptoms can initially be alleviated, the disease progresses and patients often die within two to ten years. A defining characteristic of the disease is build up of tau protein
s in neuron
s, accumulating into silver
-staining, spherical aggregations known as "Pick bodies".
While the term Pick's disease was once used to represent a class of clinical syndromes with symptoms attributable to frontal and temporal lobe dysfunction, it is now used among professionals to mean a specific pathology
that is just one of the causes of frontotemporal lobar degeneration
. Some people still use the term Pick's disease to mean the more general clinical syndrome of frontotemporal lobar degeneration, but this has previously led to confusion among both professionals and patients and so its use should be restricted to the specific pathological subtype described below. It is also known as Pick disease and PiD (not to be confused with Pelvic Inflammatory Disease (PID) or Parkinson's Disease (PD)).
, a professor of psychiatry
from the University of Prague
who first discovered and described the disease in 1892 by examining the brain tissue of several deceased patients with histories of dementia
. As a result, the characteristic histological feature of this disease—a protein tangle that appears as a large body in neuronal tissue—is named a Pick body. In 1911, Alois Alzheimer
also noted the complete absence of senile plaques and neurofilbrillary tangles as well as the presence of Pick Bodies and occasional ballooned neurons.
and progressive nonfluent aphasia
subtypes than the semantic dementia
subtype.
are associated with a genetic cause, there is no evidence in the modern literature that classical Pick's disease pathology can run in families or has a genetic cause.
antibodies have proven the most efficient and specific. Hematoxylin and eosin
staining allows visualization of another population of Pick cells, which are both tau and ubiquitin
protein negative. Several different silver
impregnation stains have been used, including the Bielschowsky, Bodian, and Gallyas methods. The latter two techniques are sensitive enough to allow PiD to be distinguished from Alzheimer's disease
as the Bodian will bind preferentially to cells with PiD as compared to the Gallyas method, which preferentially binds to the cells with Alzheimer's.
Numerous different areas of the brain are affected by PiD, but the specific areas that are affected allow for differentiation between PiD and Alzheimer’s disease. Pick bodies are almost always found in several different places in the brain, including the dentate gyrus
, the pyramidial cells of the CA1 sector and subiculum of the hippocampus
, and the neocortex as well as a plurality of other nuclei. Interestingly, it is the location within the different layers of the brain as well as the anatomical location that demonstrates some of the unique features of PiD. A striking feature is that in the neocortex the Pick bodies are located in the II and IV layers of the cortex, which send neurons within the cortex and to thalamic synapses, respectively. While layers III and V have very few if any Pick bodies they show extreme neuronal loss that can, in some cases, be so severe as to leave a void in the brain altogether. Other regions that are involved include the caudate, which is severely affected, the dorsomedial region of the putamen
, the globus pallidus
, and locus cerulus. The hypothalamic lateral tuberal nucleus is also very severely affected. The cerebellar elements that are important in receiving input, including the mossy fibers as well as the monodendritic brush cells in the granule cell layer, and generating output signals, most notably the dentate nucleus, are stricken with lots of tau protein inclusions. Strangely, the substantia nigra
is most often uninvolved or only mildly involved, but cases of extreme degeneration do exist.
PiD has several unique biochemical characteristics that allow for unique identification of Pick’s disease as opposed to other pathological subtypes of frontotemporal lobar degeneration
. The most striking of these is that this disease, which has tau protein tangles present in many affected neurons, contains only one or as many as two of the six different isoforms of the tau protein. All of these isoforms result from alternative splicing of the same gene. Pick bodies typically have the 3R isoform of tau proteins as not only the most abundant form but the only form of this protein, but a recent study has shown that a much greater number of different tau isoforms including 4R and mixed 3R/4R can be present in the Pick bodies. Not only do these tangles have the 3R tau protein predominately but they are also characteristically shaped with a round body and there is often an indentation in the area that faces the nucleus of the cell. The Pick bodies are also able to be labeled by N-terminal amyloid precursor protein segment, hyperphosphorylated tau, ubiquitin, Alz-50, neurofiliment proteins, clathrin, synaptophysin and neuronal surface glycoside (A2B5) specific stains. Moreover βII tubulin proteins are also suspected in playing a role in the formation of phosphor-tau aggregates that are seen in PiD as well as AD.
, amyloid P
, and heparan sulfate glycosaminoglycan
.
Another difference is that in Pick's disease, a personality change occurs prior to any form of memory loss
, unlike Alzheimer's
, where memory loss
typically presents first. This is used clinically to determine whether patient is suffering from Alzheimer's
or Pick's.
(FTLD)
Syndromes of frontotemporal dementia
Semantic dementia
Progressive nonfluent aphasia
Nerve
A peripheral nerve, or simply nerve, is an enclosed, cable-like bundle of peripheral axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons. Nerves are found only in the peripheral nervous system...
cells in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
. Symptoms include loss of speech (aphasia
Aphasia
Aphasia is an impairment of language ability. This class of language disorder ranges from having difficulty remembering words to being completely unable to speak, read, or write....
), and dementia. While some of the symptoms can initially be alleviated, the disease progresses and patients often die within two to ten years. A defining characteristic of the disease is build up of tau protein
Tau protein
Tau proteins are proteins that stabilize microtubules. They are abundant in neurons of the central nervous system and are less common elsewhere, but are also expressed at very low levels in CNS astrocytes and oligodendrocytes...
s in neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s, accumulating into silver
Silver
Silver is a metallic chemical element with the chemical symbol Ag and atomic number 47. A soft, white, lustrous transition metal, it has the highest electrical conductivity of any element and the highest thermal conductivity of any metal...
-staining, spherical aggregations known as "Pick bodies".
While the term Pick's disease was once used to represent a class of clinical syndromes with symptoms attributable to frontal and temporal lobe dysfunction, it is now used among professionals to mean a specific pathology
Pathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....
that is just one of the causes of frontotemporal lobar degeneration
Frontotemporal lobar degeneration
-Further reading:*Hodges, John R. The Frontotemporal Dementia Syndromes. Cambridge University Press. 2007 ISBN 978-0-521-85477-1-External links:****Mayo Clinic - **...
. Some people still use the term Pick's disease to mean the more general clinical syndrome of frontotemporal lobar degeneration, but this has previously led to confusion among both professionals and patients and so its use should be restricted to the specific pathological subtype described below. It is also known as Pick disease and PiD (not to be confused with Pelvic Inflammatory Disease (PID) or Parkinson's Disease (PD)).
History
Pick's disease is named after Arnold PickArnold Pick
Arnold Pick was a Czech neurologist and psychiatrist. He is known for identifying the clinical syndrome of Pick's Disease and the Pick bodies that are characteristic of the disorder. He was the first to name reduplicative paramnesia. He was also to use the term dementia praecox .- External links...
, a professor of psychiatry
Psychiatry
Psychiatry is the medical specialty devoted to the study and treatment of mental disorders. These mental disorders include various affective, behavioural, cognitive and perceptual abnormalities...
from the University of Prague
Charles University in Prague
Charles University in Prague is the oldest and largest university in the Czech Republic. Founded in 1348, it was the first university in Central Europe and is also considered the earliest German university...
who first discovered and described the disease in 1892 by examining the brain tissue of several deceased patients with histories of dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
. As a result, the characteristic histological feature of this disease—a protein tangle that appears as a large body in neuronal tissue—is named a Pick body. In 1911, Alois Alzheimer
Alois Alzheimer
Aloysius "Alois" Alzheimer, was a German psychiatrist and neuropathologist and a colleague of Emil Kraepelin. Alzheimer is credited with identifying the first published case of "presenile dementia", which Kraepelin would later identify as Alzheimer's disease....
also noted the complete absence of senile plaques and neurofilbrillary tangles as well as the presence of Pick Bodies and occasional ballooned neurons.
Symptoms
The symptoms of Pick's disease include difficulty in speech and thinking, behavioral changes, impaired regulation of social conduct (e.g. breaches of etiquette, tactlessness, dis-inhibition), passivity, inertia, over-activity, pacing and wandering. The changes in personality allow doctors to distinguish between Pick's disease and Alzheimer's disease. Pick's disease is one of the causes of the clinical syndrome of frontotemporal lobar degeneration which has three subtypes. Pick's disease pathology is associated more with the frontotemporal dementiaFrontotemporal dementia
Frontotemporal dementia is a clinical syndrome caused by degeneration of the frontal lobe of the brain and may extend back to the temporal lobe...
and progressive nonfluent aphasia
Progressive nonfluent aphasia
Progressive nonfluent aphasia is one of three clinical syndromes associated with frontotemporal lobar degeneration. The major symptom is progressive difficulties with the production of speech.-Clinical features:...
subtypes than the semantic dementia
Semantic dementia
Semantic dementia is a progressive neurodegenerative disorder characterized by loss of semantic memory in both the verbal and non-verbal domains...
subtype.
Causes
While other pathologies causing frontotemporal lobar degenerationFrontotemporal lobar degeneration
-Further reading:*Hodges, John R. The Frontotemporal Dementia Syndromes. Cambridge University Press. 2007 ISBN 978-0-521-85477-1-External links:****Mayo Clinic - **...
are associated with a genetic cause, there is no evidence in the modern literature that classical Pick's disease pathology can run in families or has a genetic cause.
Pathology and biochemistry
PiD was first recognized as a distinct disease separate from other neurodegenerative diseases because of the presence of large, dark-staining aggregates of proteins in neurological tissue as well as the aforementioned ballooned cells, which are known as Pick cells. Pick bodies are almost universally present in patients with PiD, but some new cases of atypical Pick’s disease have come to light that lack noticeable Pick bodies. A variety of stains can aid in the visualization of Pick bodies and Pick cells, but immunohistochemical staining using anti-tau and anti-ubiquitinUbiquitin
Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...
antibodies have proven the most efficient and specific. Hematoxylin and eosin
Eosin
Eosin is a fluorescent red dye resulting from the action of bromine on fluorescein. It can be used to stain cytoplasm, collagen and muscle fibers for examination under the microscope. Structures that stain readily with eosin are termed eosinophilic....
staining allows visualization of another population of Pick cells, which are both tau and ubiquitin
Ubiquitin
Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...
protein negative. Several different silver
Silver
Silver is a metallic chemical element with the chemical symbol Ag and atomic number 47. A soft, white, lustrous transition metal, it has the highest electrical conductivity of any element and the highest thermal conductivity of any metal...
impregnation stains have been used, including the Bielschowsky, Bodian, and Gallyas methods. The latter two techniques are sensitive enough to allow PiD to be distinguished from Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
as the Bodian will bind preferentially to cells with PiD as compared to the Gallyas method, which preferentially binds to the cells with Alzheimer's.
Numerous different areas of the brain are affected by PiD, but the specific areas that are affected allow for differentiation between PiD and Alzheimer’s disease. Pick bodies are almost always found in several different places in the brain, including the dentate gyrus
Dentate gyrus
The dentate gyrus is part of the hippocampal formation. It is thought to contribute to new memories as well as other functional roles. It is notable as being one of a select few brain structures currently known to have high rates of neurogenesis in adult rats, .The dentate gyrus cells receive...
, the pyramidial cells of the CA1 sector and subiculum of the hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
, and the neocortex as well as a plurality of other nuclei. Interestingly, it is the location within the different layers of the brain as well as the anatomical location that demonstrates some of the unique features of PiD. A striking feature is that in the neocortex the Pick bodies are located in the II and IV layers of the cortex, which send neurons within the cortex and to thalamic synapses, respectively. While layers III and V have very few if any Pick bodies they show extreme neuronal loss that can, in some cases, be so severe as to leave a void in the brain altogether. Other regions that are involved include the caudate, which is severely affected, the dorsomedial region of the putamen
Putamen
The putamen is a round structure located at the base of the forebrain . The putamen and caudate nucleus together form the dorsal striatum. It is also one of the structures that comprises the basal ganglia. Through various pathways, the putamen is connected to the substantia nigra and globus pallidus...
, the globus pallidus
Globus pallidus
The globus pallidus also known as paleostriatum, is a sub-cortical structure of the brain. Topographically, it is part of the telencephalon, but retains close functional ties with the subthalamus - both of which are part of the extrapyramidal motor system...
, and locus cerulus. The hypothalamic lateral tuberal nucleus is also very severely affected. The cerebellar elements that are important in receiving input, including the mossy fibers as well as the monodendritic brush cells in the granule cell layer, and generating output signals, most notably the dentate nucleus, are stricken with lots of tau protein inclusions. Strangely, the substantia nigra
Substantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
is most often uninvolved or only mildly involved, but cases of extreme degeneration do exist.
PiD has several unique biochemical characteristics that allow for unique identification of Pick’s disease as opposed to other pathological subtypes of frontotemporal lobar degeneration
Frontotemporal lobar degeneration
-Further reading:*Hodges, John R. The Frontotemporal Dementia Syndromes. Cambridge University Press. 2007 ISBN 978-0-521-85477-1-External links:****Mayo Clinic - **...
. The most striking of these is that this disease, which has tau protein tangles present in many affected neurons, contains only one or as many as two of the six different isoforms of the tau protein. All of these isoforms result from alternative splicing of the same gene. Pick bodies typically have the 3R isoform of tau proteins as not only the most abundant form but the only form of this protein, but a recent study has shown that a much greater number of different tau isoforms including 4R and mixed 3R/4R can be present in the Pick bodies. Not only do these tangles have the 3R tau protein predominately but they are also characteristically shaped with a round body and there is often an indentation in the area that faces the nucleus of the cell. The Pick bodies are also able to be labeled by N-terminal amyloid precursor protein segment, hyperphosphorylated tau, ubiquitin, Alz-50, neurofiliment proteins, clathrin, synaptophysin and neuronal surface glycoside (A2B5) specific stains. Moreover βII tubulin proteins are also suspected in playing a role in the formation of phosphor-tau aggregates that are seen in PiD as well as AD.
Differences from Alzheimer’s disease
In Alzheimer’s disease, all six isoforms of tau proteins are expressed. In addition, the presence of neurofibrillary tangles that are a hallmark of Alzheimer’s can be stained with antibodies to basic fibroblast growth factorBasic fibroblast growth factor
Basic fibroblast growth factor, also known as bFGF, FGF2 or FGF-β, is a member of the fibroblast growth factor family.- Function :...
, amyloid P
Serum Amyloid P component
Amyloid P component, serum is the identical serum form of amyloid P component , a 25kDa pentameric protein first identified as the pentagonal constituent of in vivo pathological deposits called "amyloid"...
, and heparan sulfate glycosaminoglycan
Heparan sulfate
Heparan sulfate is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins...
.
Another difference is that in Pick's disease, a personality change occurs prior to any form of memory loss
Memory loss
Memory loss can be partial or total and it is normal when it comes with aging. Sudden memory loss is usually a result of brain trauma and it may be permanent or temporary. When it is caused by medical conditions such as Alzheimers, the memory loss is gradual and tends to be permanent.Brain trauma...
, unlike Alzheimer's
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
, where memory loss
Memory loss
Memory loss can be partial or total and it is normal when it comes with aging. Sudden memory loss is usually a result of brain trauma and it may be permanent or temporary. When it is caused by medical conditions such as Alzheimers, the memory loss is gradual and tends to be permanent.Brain trauma...
typically presents first. This is used clinically to determine whether patient is suffering from Alzheimer's
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
or Pick's.
See also
Frontotemporal lobar degenerationFrontotemporal lobar degeneration
-Further reading:*Hodges, John R. The Frontotemporal Dementia Syndromes. Cambridge University Press. 2007 ISBN 978-0-521-85477-1-External links:****Mayo Clinic - **...
(FTLD)
Syndromes of frontotemporal dementia
Frontotemporal dementia
Frontotemporal dementia is a clinical syndrome caused by degeneration of the frontal lobe of the brain and may extend back to the temporal lobe...
Semantic dementia
Semantic dementia
Semantic dementia is a progressive neurodegenerative disorder characterized by loss of semantic memory in both the verbal and non-verbal domains...
Progressive nonfluent aphasia
Progressive nonfluent aphasia
Progressive nonfluent aphasia is one of three clinical syndromes associated with frontotemporal lobar degeneration. The major symptom is progressive difficulties with the production of speech.-Clinical features:...
External links
- Pick bodies (histology)
- Frontotemporal Dementia Information Page from the National Institute of Neurological Disorders and StrokeNational Institute of Neurological Disorders and StrokeThe National Institute of Neurological Disorders and Stroke is a part of the U.S. National Institutes of Health . It conducts and funds research on brain and nervous system disorders and has a budget of just over US$1.5 billion...
- Pick's Disease Information Page
- Frontotemporal dementia information and videos from the UCSF Memory and Aging Center
- The Bluefield Project to Cure Frontotemporal Dementia
- Pick's Disease: Signs, Symptoms, Treatment, and Support