Pick's disease, a type of frontotemporal dementia, is a rare neurodegenerative
disease that causes progressive destruction of nerve cells in the brain.
Symptoms include dementia and loss of language. 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 proteins in neurons, 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 one of
the causes of frontotemporal lobar degeneration. Some people 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
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 or
Parkinson's disease). Signs and symptoms
The symptoms of Pick's disease include difficulty in language and thinking,
efforts to dissociate from family, behavioral changes, unwarranted anxiety,
impaired regulation of social conduct, passivity, low motivation, 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 dementia and progressive nonfluent aphasia
subtypes than the semantic dementia subtype.
Causes While other pathologies causing
frontotemporal lobar degeneration are associated with a genetic cause,
evidence is not conclusive in modern research on whether classical Pick's
disease pathology has or does not have a direct genetic link, or whether it has
been shown to run in families or certain ethnic or gender specific subgroups.
However, excess of a protein called β-amyloid in neural cells has been
linked to neural degeneration. A buildup of Aβ within cells causes inflammation,
leading to cell destruction by the immune system. Proteins associated with
Pick's disease are present in all nerve cells, but those with the disease have
an abnormal amount. Mutations in the tau gene have been
associated with this disease. Pathophysiology
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-ubiquitin 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 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 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 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 in the
layers of the brain as well as the anatomical placement that demonstrates
some of the unique features of PiD. A striking feature is that in the
neocortex the Pick bodies are 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 coeruleus. 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
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 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 some studies have
shown that a much greater number of 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, they are characteristically shaped with a round
body; there is often an indentation in the area that faces the nucleus of the
cell. The Pick bodies are able to be labeled
by N-terminal amyloid precursor protein segment, hyperphosphorylated tau,
ubiquitin, Alz-50, neurofiliment proteins, clathrin, synaptophysin and
neuronal surface glycoside specific stains. Moreover βII tubulin proteins
are 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 factor, amyloid P, and heparan sulfate glycosaminoglycan.
Another difference is that in Pick's disease, a personality change occurs
before any form of memory loss, unlike Alzheimer's, where memory loss typically
presents first. This is used clinically to determine whether a patient is
suffering from Alzheimer's or Pick's. History
Pick's disease is named after Arnold Pick, a professor of psychiatry from
Charles University in 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 noted the complete
absence of senile plaques and neurofilbrillary tangles as well as the
presence of Pick bodies and occasional ballooned neurons.
Notable cases Don Cardwell, Major League baseball
pitcher Colleen Howe, sports agent and hockey
team manager, known as "Mrs. Hockey" Kevin Moore, English footballer
Nic Potter, British bassist for Van der Graaf Generator
Colin Savage, father of footballer Robbie Savage
Ernie Moss, English footballer. See also
Frontotemporal lobar degeneration Syndromes of frontotemporal dementia
Semantic dementia Progressive nonfluent aphasia
References Pick A. Über die Beziehungen der senilen
Hirnatrophie zur Aphasie. Prager medicinische Wochenschrift Prague
17:165-167. External links
Pick bodies Frontotemporal Dementia Information Page
from the National Institute of Neurological Disorders and Stroke
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 Australian Frontal-Temporal Dementia
Association for carers and service providers