Pick%27s disease

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 speech (aphasia). 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 (not to be confused with pelvic inflammatory disease (PID) or Parkinson's disease (PD)).

Signs and symptoms

The symptoms of Pick's disease include difficulty in speech and thinking, efforts to dissociate from family, behavioral changes, unwarranted anxiety, impaired regulation of social conduct (e.g., breaches of etiquette, tactlessness, dis-inhibition, misperception), 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 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.

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 a recent study has 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 (A2B5) 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 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 diseaseâ€"a protein tangle that appears as a large body in neuronal tissueâ€"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 (1935â€"2008), Major League baseball pitcher
• Rocco "Rocky" Catena (1929â€"2006), music industry executive, former senior VP, Capitol Records, in charge of marketing The Beatles and other top recording stars in the U.S. Suffered from Pick's disease for 20+ years.
• Jerry Corbetta (1947-), original lead singer and keyboardist for the group Sugarloaf
• Ted Darling (c.1935â€"1996), voice of the Buffalo Sabres
• Robert W. Floyd (1936â€"2001), computer scientist
• Colleen Howe (1933â€"2009), wife of Hockey Hall of Famer Gordie Howe
• Kazi Nazrul Islam (1899â€"1976), Bengali poet and musician (Known as rebel poet), who pioneered poetic works espousing intense rebellion against fascism and oppression, was a lifelong sufferer of this disease (approximately 1941â€"1976)
• Ralph Klein (1942â€"2013), former premier of Alberta, Canada
• Kevin Moore (1958â€"2013), English footballer
• Nic Potter (1951â€"2013), British bassist for Van der Graaf Generator
• David Rumelhart (1942â€"2011), American cognitive psychologist
• Colin Savage, father of footballer Robbie Savage
• Ernie Moss (born 1949), English footballer.