- Pick's disease
Name = PAGENAME
DiseasesDB = 10034
ICD10 = ICD10|G|31|0|g|30, ICD10|F|02|0|f|00
ICD9 = ICD9|331.11
OMIM = 172700
eMedicineSubj = neuro
eMedicineTopic = 311
MeshID = D020774
Pick’s disease, also known as Pick disease and PiD, is a rare
neurodegenerative disease. While the term Pick's disease was once used to represent a specific group of clinical syndromes with symptoms attributable to frontal and temporal lobe dysfunction, it is now used (at least among professionals in the field) to mean a specific pathology that is just one of the causes of this clinical syndrome (now known as frontotemporal lobar degeneration). Some people still use the term Pick's disease to mean the clinical syndrome of frontotemporal lobar degenerationbut 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.
Pick's disease (the pathology) causes progressive destruction of
nervecells in the brainand causes tau proteins to accumulate into " Pick bodies"cite journal | last = Wang | first = LN | coauthors = Zhu MW, Feng YQ, Wang JH.| title = Pick's disease with Pick bodies combined with progressive supranuclear palsy without tuft-shaped astrocytes: a clinical, neuroradiologic and pathological study of an autopsied case | journal = Neuropathology | volume = 26 | issue = 3 | pages = 222–230 | year = 2006 | pmid = 16771179| doi = 10.1111/j.1440-1789.2006.00671.x] that are a defining characteristic of the disease.
Pick 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 cite journal | last = Amano | first = N | coauthors = Iseki, E | title = Introduction: Pick’s disease and frontotemporal dementia | journal = Neuropathology | volume = 19 | issue = 1 | pages = 417–421 | year = 1999 | doi = 10.1046/j.1440-1789.1999.00258.x] . 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 Alzheimeralso noted the complete absence of senile plaques and neurofilbrillary tangles as well as the presence of Pick Bodies and occasional ballooned neurons.
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 dementiaand progressive nonfluent aphasiasubtypes than the semantic dementiasubtype.
Whilst other pathologies causing
frontotemporal lobar degenerationare 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.
The Pathology and Biochemistry of Pick’s Disease
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 bodiescite journal | last = Yamakawa | first = K | coauthors = Takanashi M, Watanabe M, Nakamura N, Kobayashi T, Hasegawa M, Mizuno Y, Tanaka S, Mori H | title = Pathological and biochemical studies on a case of Pick disease with severe white matter atrophy| journal = Neuropathology | volume = 26 | issue = 6 | pages = 586–591 | year = 2006 | pmid = 17203597 | doi = 10.1111/j.1440-1789.2006.00738.x] . A variety of stains that can aid in the visualization of Pick bodies and Pick cells, but
immunohistochemical stainingusing anti-tau and anti-ubiquitin antibodieshave proven the most efficient and specific cite journal | last = Armstrong | first = RA | coauthors = Cairns NJ, Lantos, PL | title = A comparison of histological and immunohistochemical methods for quantifying the pathological lesions of Pick’s disease | journal = Neuropathology | volume = 18 | issue = 4 | pages = 295–300 | year = 1998 | pmid = 16006664 | doi = 10.1111/j.1440-1789.1998.tb00118.x] . Hematoxylinand eosinstaining allows visualization of another population of Pick cells, which are both tau and ubiquitinprotein negative. Several different silver impregnation stains have been used, including the Bielschowsky, Bodian, and Gallyas methodscite journal | last = Uchihara | first = T | coauthors = Ikeda K, Tsuchiya K.| title = Pick body disease and Pick syndrome| journal = Neuropathology | volume = 23 | issue = 4 | pages = 318–326 | year = 2003 | pmid = 14719549| doi = 10.1046/j.1440-1789.2003.00523.x] cite journal | last = Yamakawa | first = K | coauthors = Takanashi M, Watanabe M, Nakamura N, Kobayashi T, Hasegawa M, Mizuno Y, Tanaka S, Mori H | title = Pathological and biochemical studies on a case of Pick disease with severe white matter atrophy| journal = Neuropathology | volume = 26 | issue = 6 | pages = 586–591 | year = 2006 | pmid = 17203597 | doi = 10.1111/j.1440-1789.2006.00738.x] . The latter two techniques are sensitive enough to allow PiD to be distinguished from AD as the Bodian will bind preferentially to cells with PiD as compared to the Gallyas method, which preferentially binds to the cells with AD.
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 (AD). The aforementioned 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 nigrais 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.cite journal | last = Iskei | first = E | coauthors = Arai, H | title = Progress in the classification of non-Alzheimer-type degenerative dementias | journal = Psychogeriactrics | volume = 6 | issue = 1 | pages = 41–42 | year = 2006 | doi = 10.1111/j.1479-8301.2006.00166.x] All of these isoforms result from alternative splicing of the same gene. [cite journal | last = Arai | first = T | coauthors = Ikeda K, Akiyama H, Tsuchiya K, Iritani S, Ishiguro K, Yagishita S, Oda T, Odawara T, Iseki E.| title = Different immunoreactivities of the microtubule-binding region of tau and its molecular basis in brains from patients with Alzheimer's disease, Pick's disease, progressive supranuclear palsy, and corticobasal degeneration | journal = Acta Neuropathol.| volume = 105 | issue = 5 | pages = 489–498 | year = 2003 | pmid = 12677450| doi = 10.1007/s00401-003-0671-8] 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.cite journal | last = Munoz | first = DG | coauthors = Dickson DW, Bergeron C, Mackenzie IR, Delacourte A, Zhukareva V. | title = The neuropathology and biochemistry of frontotemporal dementia | journal = Ann Neurol | volume = 54 supp. S5 | issue = 1 | pages = S24–S28 | year = 2003 | pmid = 12833365 | doi = 10.1002/ana.10571] 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. [cite journal | last = Puig | first = B | coauthors = Ferrer I, Ludueña RF, Avila J.| title = βII-tubulin and phospho-tau aggregates in Alzheimer's disease and Pick's disease| journal = J Alzheimers Dis.| volume = 7 | issue = 1 | pages = 213–220 | year = 2005 | pmid = 16006664]
Differences from Alzheimer’s disease
In AD all six isoforms of tau proteins expressed. In addition, the presence of neurofibrillary tangles that are a hallmark of AD can be stained with antibodies to basic fibroblast growth factor, amyloid P, and heparan sulfate glycosaminoglycan.
* [http://www.ftdsupportforum.com/ FTD Support Forum]
* [http://www.ftd-picks.org/ The Association for Frontotemporal Dementias]
* [http://memory.ucsf.edu UCSF Memory and Aging Center] - [http://memory.ucsf.edu/resources.html#ftd FTD Resources] and [http://memory.ucsf.edu/Education/Disease/ftd.html FTD Info]
*Mayo Clinic - [http://www.mayoclinic.com/invoke.cfm?id=AN00541 FTD Info]
* [http://www.pdsg.org.uk/ Pick's Disease Support Group Online]
* [http://www.ftdsupport.com/ Frontotemporal Dementia Caregiver Support Center]
For more information on Pick's Disease, see the article on the pathologic process of
frontotemporal lobar degeneration(FTLD) and its related clinical syndromesof frontotemporal dementia, semantic dementia, and progressive nonfluent aphasia.
* [http://www.pdsg.org.uk/ Pick's Disease Support Group Online (UK-based)]
* [http://www.bhoffcomp.com/coping/picks.html Pick's Disease Information Page]
* [http://www.ftdsupport.com Frontotemporal Dementia Caregiver Support Center]
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