pick disease of the brain


Summary: A rare form of DEMENTIA that is sometimes familial. Clinical features include APHASIA; APRAXIA; CONFUSION; ANOMIA; memory loss; and personality deterioration. This pattern is consistent with the pathologic findings of circumscribed atrophy of the poles of the FRONTAL LOBE and TEMPORAL LOBE. Neuronal loss is maximal in the HIPPOCAMPUS, entorhinal cortex, and AMYGDALA. Some ballooned cortical neurons contain argentophylic (Pick) bodies. (From Brain Pathol 1998 Apr;8(2):339-54; Adams et al., Principles of Neurology, 6th ed, pp1057-9)

Top Publications

  1. Fehér A, Juhász A, Rimanóczy A, Kalman J, Janka Z. Association between BDNF Val66Met polymorphism and Alzheimer disease, dementia with Lewy bodies, and Pick disease. Alzheimer Dis Assoc Disord. 2009;23:224-8 pubmed publisher
    ..We suggest that the presence of the BDNF Val allele in itself and in combination with the ApoE epsilon4 allele can be risk factors for AD, and the results indicate a synergistic effect of the 2 polymorphisms on DLB and PiD risk. ..
  2. Takeda N, Kishimoto Y, Yokota O. Pick's disease. Adv Exp Med Biol. 2012;724:300-16 pubmed publisher
  3. Uchihara T, Ikeda K, Tsuchiya K. Pick body disease and Pick syndrome. Neuropathology. 2003;23:318-26 pubmed
    ..This will provide a practical basis on which to differentiate these disorders based on their distinctive tau species and possible relation of tau species to staining profile on these silver methods. ..
  4. Piguet O, Halliday G, Reid W, Casey B, Carman R, Huang Y, et al. Clinical phenotypes in autopsy-confirmed Pick disease. Neurology. 2011;76:253-9 pubmed publisher
    ..These findings have relevance as treatment options, which are likely to be pathology specific, are developed. ..
  5. Kertesz A. Frontotemporal dementia, Pick's disease. Ideggyogy Sz. 2010;63:4-12 pubmed
    ..Tau and progranulin mutations on Ch-17 and some others, point to molecular mechanisms. A glossary is provided to navigate the complex terminology. ..
  6. Davies R, Hodges J, Kril J, Patterson K, Halliday G, Xuereb J. The pathological basis of semantic dementia. Brain. 2005;128:1984-95 pubmed
  7. Kalman J, Juhasz A, Majtenyi K, Rimanoczy A, Jakab K, Gardian G, et al. Apolipoprotein E polymorphism in Pick's disease and in Huntington's disease. Neurobiol Aging. 2000;21:555-8 pubmed
  8. Rohrer J, Lashley T, Schott J, Warren J, Mead S, Isaacs A, et al. Clinical and neuroanatomical signatures of tissue pathology in frontotemporal lobar degeneration. Brain. 2011;134:2565-81 pubmed publisher
  9. Kertesz A, McMonagle P, Blair M, Davidson W, Munoz D. The evolution and pathology of frontotemporal dementia. Brain. 2005;128:1996-2005 pubmed

More Information


  1. Yokota O, Tsuchiya K, Arai T, Yagishita S, Matsubara O, Mochizuki A, et al. Clinicopathological characterization of Pick's disease versus frontotemporal lobar degeneration with ubiquitin/TDP-43-positive inclusions. Acta Neuropathol. 2009;117:429-44 pubmed publisher
  2. Gao S, Yu R, Zhou X. The Role of Geranylgeranyltransferase I-Mediated Protein Prenylation in the Brain. Mol Neurobiol. 2016;53:6925-6937 pubmed
  3. Pamplona R, Ilieva E, Ayala V, Bellmunt M, Cacabelos D, Dalfo E, et al. Maillard reaction versus other nonenzymatic modifications in neurodegenerative processes. Ann N Y Acad Sci. 2008;1126:315-9 pubmed
    ..In addition, these findings suggest the lack of a "gold marker of oxidative stress," and, consequently, they strengthen the need for a molecular dissection of the nonenzymatic reactions underlying neurodegenerative processes. ..
  4. Boxer A, Miller B. Clinical features of frontotemporal dementia. Alzheimer Dis Assoc Disord. 2005;19 Suppl 1:S3-6 pubmed
  5. Derouesné C. [From Arnold Pick's original descriptions to frontotemporal dementia: the present enlightened by the past an historical approach]. Geriatr Psychol Neuropsychiatr Vieil. 2014;12:74-84 pubmed publisher
  6. Oda T, Tsuchiya K, Arai T, Togo T, Uchikado H, de Silva R, et al. Pick's disease with Pick bodies: an unusual autopsy case showing degeneration of the pontine nucleus, dentate nucleus, Clarke's column, and lower motor neuron. Neuropathology. 2007;27:81-9 pubmed
    ..The atypical clinical symptoms and the widespread neuropathological abnormalities observed in this case seem to represent an extremely extended form of PDPB. ..
  7. Kawashima T, Furuta A, Doh ura K, Kikuchi H, Iwaki T. Ubiquitin-immunoreactive skein-like inclusions in the neostriatum are not restricted to amyotrophic lateral sclerosis, but are rather aging-related structures. Acta Neuropathol. 2000;100:43-9 pubmed
    ..Our findings indicate that SLI in the neostriatum are ubiquitin-related structures whose occurrence increases by aging, and less frequently accompany several neurodegenerative diseases, and are identical to at least some RLI. ..
  8. Hasegawa M, Arai T, Akiyama H, Nonaka T, Mori H, Hashimoto T, et al. TDP-43 is deposited in the Guam parkinsonism-dementia complex brains. Brain. 2007;130:1386-94 pubmed
    ..These results suggest that accumulation of TDP-43 is a common process in certain neurodegenerative disorders, including FTLD-U, ALS and G-PDC. ..
  9. Dougherty M, Lazar J, Klein J, Diaz K, Gobillot T, Grunblatt E, et al. Genome sequencing in a case of Niemann-Pick type C. Cold Spring Harb Mol Case Stud. 2016;2:a001222 pubmed
    ..In light of these findings, this case provides support for the V950M variant being sufficient for adult-onset NPC disease. ..
  10. Fehér A, Juhász A, Rimanóczy A, Csibri E, Kalman J, Janka Z. Association between a genetic variant of the alpha-7 nicotinic acetylcholine receptor subunit and four types of dementia. Dement Geriatr Cogn Disord. 2009;28:56-62 pubmed publisher
    ..We confirmed again that the ApoE epsilon4 allele is a risk factor for dementias. The -2 bp polymorphism of CHRFAM7A can be implicated in AD, DLB and PiD. However, it is unlikely that it plays an important role in the pathogenesis of VD. ..
  11. Laurin D, Masaki K, White L, Launer L. Ankle-to-brachial index and dementia: the Honolulu-Asia Aging Study. Circulation. 2007;116:2269-74 pubmed
    ..43; 95% CI, 1.02 to 1.96). These results suggest that ABI, a measure of atherosclerosis, is associated with the incidence of total dementia, vascular dementia, and Alzheimer's disease in carriers of the apolipoprotein E epsilon4 allele. ..
  12. Kril J, Macdonald V, Patel S, Png F, Halliday G. Distribution of brain atrophy in behavioral variant frontotemporal dementia. J Neurol Sci. 2005;232:83-90 pubmed
    ..This suggests that the regional pattern of neurodegeneration, rather than the type of histopathology influences the clinical syndrome in FTD. ..
  13. Haberland C. Frontotemporal dementia or frontotemporal lobar degeneration--overview of a group of proteinopathies. Ideggyogy Sz. 2010;63:87-93 pubmed
    ..Genetic factors play an important part in the etiologies of dementias. This article overviews current defining characteristics of frontotemporal dementias known also as frontotemporal lobar degenerations. ..
  14. Zatta P, Zambenedetti P, Musicco M, Adorni F. Metallothionein-I-II and GFAP positivity in the brains from frontotemporal dementia patients. J Alzheimers Dis. 2005;8:109-16; discussion 209-15 pubmed
    ..In addition, the potential use of metallothionein-I-II as a new pharmacological approach to contrast some deleterious aspects of this disease has been also discussed. ..
  15. Kimonis V, Watts G. Autosomal dominant inclusion body myopathy, Paget disease of bone, and frontotemporal dementia. Alzheimer Dis Assoc Disord. 2005;19 Suppl 1:S44-7 pubmed
    ..Identification of VCP as the gene causing IBMPFD has important implications for understanding the pathogenesis of neurodegenerative disorders. ..
  16. Mimura M, Oda T, Tsuchiya K, Kato M, Ikeda K, Hori K, et al. Corticobasal degeneration presenting with nonfluent primary progressive aphasia: a clinicopathological study. J Neurol Sci. 2001;183:19-26 pubmed
    ..The clinical manifestations in CBD are diverse, and primary progressive nonfluent aphasia should be considered as an initial symptom of CBD. Neuropathological examination of such patients should include cytoskeletal abnormality studies. ..
  17. Russ C, Lovestone S, Baker M, Pickering Brown S, Andersen P, Furlong R, et al. The extended haplotype of the microtubule associated protein tau gene is not associated with Pick's disease. Neurosci Lett. 2001;299:156-8 pubmed
    ..We therefore investigated whether either the tau H1 or H2 haplotype was associated with PiD. Our results indicate a slight increase in H2H2 frequency in Pick's cases which is not statistically significant. ..
  18. Hardin S, Schooley B. A story of Pick's disease: a rare form of dementia. J Neurosci Nurs. 2002;34:117-22 pubmed
    ..Nurses have the responsibility of educating the primary caregiver about nutrition, skin protection, incontinence care, safety, and end-of-life decisions. ..
  19. van Eersel J, Bi M, Ke Y, Hodges J, Xuereb J, Gregory G, et al. Phosphorylation of soluble tau differs in Pick's disease and Alzheimer's disease brains. J Neural Transm (Vienna). 2009;116:1243-51 pubmed publisher
    ..Such differences in solubility and phosphorylation may contribute, at least in part, to the formation of distinct tau deposits, but may also have implications for the clinical differences between AD and PiD. ..
  20. Hartzler A, Zhu X, Siedlak S, Castellani R, Avila J, Perry G, et al. The p38 pathway is activated in Pick disease and progressive supranuclear palsy: a mechanistic link between mitogenic pathways, oxidative stress, and tau. Neurobiol Aging. 2002;23:855-9 pubmed
    ..Based on these findings, we propose that the phosphorylation of tau is a direct consequence of the oxidative stress-induced activation of mitogen-activated protein kinases, including p38. ..
  21. Buee L, Delacourte A. Comparative biochemistry of tau in progressive supranuclear palsy, corticobasal degeneration, FTDP-17 and Pick's disease. Brain Pathol. 1999;9:681-93 pubmed
    ..Thus, tau mutations and polymorphisms may also be instrumental in many neurodegenerative disorders. ..
  22. Peng F. Is dementia a disease?. Gerontology. 2003;49:384-91 pubmed
    ..It is also suggested that in fairness to Fischer, senile plaques be designated as Fischer's disease separate from neurofibrillary tangles for which AD was originally named as an eponym. ..
  23. Sedel F, Chabrol B, Audoin B, Kaphan E, Tranchant C, Burzykowski T, et al. Normalisation of brain spectroscopy findings in Niemann-Pick disease type C patients treated with miglustat. J Neurol. 2016;263:927-936 pubmed publisher
    ..04) and 0.55 (0.09), respectively. In conclusion, H-MRS Cho/NAA ratio might serve as an objective, quantitative neurological marker of brain dysfunction in NP-C, allowing longitudinal analysis of the therapeutic effect of miglustat. ..
  24. Code C, Tree J, Ball M. The influence of psycholinguistic variables on articulatory errors in naming in progressive motor speech degeneration. Clin Linguist Phon. 2011;25:1074-80 pubmed publisher
    ..Results suggest that C.S.'s speech and naming errors indicate compromised speech programming/planning rather than lexical selection and we conclude that this pattern of findings is indicative of problems with motor speech production...
  25. Rizzini C, Goedert M, Hodges J, Smith M, Jakes R, Hills R, et al. Tau gene mutation K257T causes a tauopathy similar to Pick's disease. J Neuropathol Exp Neurol. 2000;59:990-1001 pubmed
    ..Taken together, the present findings indicate that the K257T mutation in Tau can cause a dementing condition similar to Pick's disease. ..
  26. Tozza S, Dubbioso R, Iodice R, Topa A, Esposito M, Ruggiero L, et al. Long-term therapy with miglustat and cognitive decline in the adult form of Niemann-Pick disease type C: a case report. Neurol Sci. 2018;39:1015-1019 pubmed publisher
    ..Our findings suggest that long-term therapy with miglustat does not arrest cognitive decline; otherwise, it stabilizes other neurological manifestations. ..
  27. Wysokiński A, Gruszczyński W. [Diagnostic difficulties linked to frontotemporal dementia--case study]. Psychiatr Pol. 2008;42:377-82 pubmed
    ..Despite the treatment with drugs of different groups was conducted, no stable positive outcome was obtained. ..
  28. Cuisset J, Sukno S, Trauffler A, Latour P, Dobbelaere D, Michaud L, et al. Impact of miglustat on evolution of atypical presentation of late-infantile-onset Niemann-Pick disease type C with early cognitive impairment, behavioral dysfunction, epilepsy, ophthalmoplegia, and cerebellar involvement: a case report. J Med Case Rep. 2016;10:241 pubmed publisher
    ..Thus the therapeutic efficacy of miglustat could be hypothesized as a substrate reduction effect on Purkinje cells. ..
  29. Mann D. Frontotemporal lobar degeneration--a coming of age. Acta Neuropathol. 2007;114:1-4 pubmed
  30. Ando K, Tomimura K, Sazdovitch V, Suain V, Yilmaz Z, Authelet M, et al. Level of PICALM, a key component of clathrin-mediated endocytosis, is correlated with levels of phosphotau and autophagy-related proteins and is associated with tau inclusions in AD, PSP and Pick disease. Neurobiol Dis. 2016;94:32-43 pubmed publisher
    ..These results suggest that there is a close relationship between abnormal PICALM processing, tau pathology and impairment of autophagy in human neurodegenerative diseases. ..
  31. Takahashi M, Uchikado H, Caprotti D, Weidenheim K, Dickson D, Ksiezak Reding H, et al. Identification of G-protein coupled receptor kinase 2 in paired helical filaments and neurofibrillary tangles. J Neuropathol Exp Neurol. 2006;65:1157-69 pubmed
    ..Our studies indicate that GRK2 is a novel component of neuronal and glial fibrillary tau deposits with no preference in tau isoform binding. GRK2 may play a role in hyperphosphorylation of tau in tauopathies. ..
  32. Tudor L, Sikiric P, Tudor K, Cambi Sapunar L, Radonić V, Tudor M, et al. [Amusia and aphasia of Bolero's creator--influence of the right hemisphere on music]. Acta Med Croatica. 2008;62:309-16 pubmed
    ..Indeed, in these last music works one can feel the predominance of changes in pitch (timbre), i. e. right hemisphere, in comparison to only few changes of melody (left hemisphere). ..
  33. Han L, Nishimura K, Sadat Al Hosseini H, Bianchi E, Wright G, Jovine L. Divergent evolution of vitamin B9 binding underlies Juno-mediated adhesion of mammalian gametes. Curr Biol. 2016;26:R100-1 pubmed publisher
  34. Wang L, Zhu M, Feng Y, Wang J. 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. Neuropathology. 2006;26:222-30 pubmed
    ..In conclusion, these histopathological features were compatible with classical Pick's disease and coexistence with progressive supranuclear palsy without tuft-shaped astrocytes. ..
  35. Abdul Hammed M, Breiden B, Schwarzmann G, Sandhoff K. Lipids regulate the hydrolysis of membrane bound glucosylceramide by lysosomal β-glucocerebrosidase. J Lipid Res. 2017;58:563-577 pubmed publisher
    ..Our data suggest that these strong modifiers of GlcCer hydrolysis affect the genotype-phenotype correlation in several cases of Gaucher patients independent of the types. ..
  36. Palmer H. The view from 1946: mental disorders of old age, part I. Geriatrics. 2006;61:23-6 pubmed
  37. Yeaworth R. Use of the Internet in survey research. J Prof Nurs. 2001;17:187-93 pubmed
    ..J Prof Nurs 17:187-193, 2001. ..
  38. Kertesz A. Pick complex--historical introduction. Alzheimer Dis Assoc Disord. 2007;21:S5-7 pubmed
    ..A historical perspective helps to prevent the chaos of terminological confusion and reinventing the wheel. ..
  39. Schmökel V, Memar N, Wiekenberg A, Trotzmüller M, Schnabel R, Döring F. Genetics of Lipid-Storage Management in Caenorhabditis elegans Embryos. Genetics. 2016;202:1071-83 pubmed publisher
    ..elegans embryos. Owing to the high levels of conservation, the identified genes are also useful in studies of embryonic lipid storage in other organisms. ..
  40. Danev S, St Stoyanov D. Early noninvasive diagnosis of neurodegenerative diseases. Folia Med (Plovdiv). 2010;52:5-13 pubmed
    ..In conclusion, beta-pathies are considered a suitable example for the modern concept of cluster and prototype diagnosis in medicine and especially in clinical neurosciences. ..
  41. Ikeda K. [FTLD-U and Pick disease without Pick bodies--a clinical and pathological review]. Brain Nerve. 2009;61:1328-36 pubmed
    ..Thus, conventional Pick disease was further classified into Pick disease, FTLD-MND, FTLD-U (in a narrow sense), and DLDH. ..
  42. Kertesz A, Munoz D. Frontotemporal dementia. Med Clin North Am. 2002;86:501-18, vi pubmed
    ..This article emphasizes the considerable overlap among the different varieties of frontotemporal dementia, as well as the distinctive features of each...
  43. Cairns N, Armstrong R. Quantification of the pathological changes in the temporal lobe of patients with a novel neurofilamentopathy: neurofilament inclusion disease (NID). Clin Neuropathol. 2004;23:107-12 pubmed
  44. Sansare A, Zampieri C, Alter K, Stanley C, Farhat N, Keener L, et al. Gait, Balance, and Coordination Impairments in Niemann Pick Disease, Type C1. J Child Neurol. 2018;33:114-124 pubmed publisher
    ..These results can provide insight to clinical researchers on the selection of outcome measures for longitudinal and interventional studies...
  45. Ebner L, Glaser A, Bräuer A, Witt M, Wree A, Rolfs A, et al. Evaluation of Two Liver Treatment Strategies in a Mouse Model of Niemann-Pick-Disease Type C1. Int J Mol Sci. 2018;19: pubmed publisher
    ..However, HP?CD monotherapy additionally increased cholesterol synthesis as indicated by a marked increase of the HMG-CoA and srebp-2 mRNA expression, probably as a result of increased hepatocellular proliferation. ..
  46. Schwerd T, Pandey S, Yang H, Bagola K, Jameson E, Jung J, et al. Impaired antibacterial autophagy links granulomatous intestinal inflammation in Niemann-Pick disease type C1 and XIAP deficiency with NOD2 variants in Crohn's disease. Gut. 2017;66:1060-1073 pubmed publisher
    ..Muramyl dipeptide-driven cytokine responses and antibacterial autophagy induction are parallel and independent signalling cascades downstream of the NOD2-RIPK2-XIAP complex. ..
  47. Ikeda K, Akiyama H, Arai T, Ueno H, Tsuchiya K, Kosaka K. Morphometrical reappraisal of motor neuron system of Pick's disease and amyotrophic lateral sclerosis with dementia. Acta Neuropathol. 2002;104:21-8 pubmed
    ..However, the border between the two group is not always clear and there are patients who can not be definitively classified. ..
  48. Tsuchiya K, Ikeda K. Basal ganglia lesions in 'Pick complex': a topographic neuropathological study of 19 autopsy cases. Neuropathology. 2002;22:323-36 pubmed
    ..In addition, nigral involvement was usually found in CBD and gvPD, but was rarely seen in PDPB. These neuropathological findings may help to elucidate the pathological heterogeneity of basal ganglia lesions in 'Pick complex'. ..
  49. McKhann G, Albert M, Grossman M, Miller B, Dickson D, Trojanowski J. Clinical and pathological diagnosis of frontotemporal dementia: report of the Work Group on Frontotemporal Dementia and Pick's Disease. Arch Neurol. 2001;58:1803-9 pubmed
    ..In addition, recommendations for the neuropathological criteria of FTD were reviewed, relative to classical neuropathology and modern molecular biology. ..
  50. Josephs K, Whitwell J, Jack C, Parisi J, Dickson D. Frontotemporal lobar degeneration without lobar atrophy. Arch Neurol. 2006;63:1632-8 pubmed
    ..Consequently, FTLD-U without HpScl does not conform to the proposed FTLD staging scheme, is underrecognized, and may have different genetic and environmental underpinnings. ..
  51. Katsuse O, Dickson D. Ubiquitin immunohistochemistry of frontotemporal lobar degeneration differentiates cases with and without motor neuron disease. Alzheimer Dis Assoc Disord. 2005;19 Suppl 1:S37-43 pubmed
    ..These features were similar to ALS, but different from FTLD-MNI. The findings suggest that FTLD-MNI has a different pathogenesis from FTLD-MND and ALS. ..
  52. Jiang X, Sidhu R, Mydock McGrane L, Hsu F, Covey D, Scherrer D, et al. Development of a bile acid-based newborn screen for Niemann-Pick disease type C. Sci Transl Med. 2016;8:337ra63 pubmed publisher
    ..Quantification of the bile acid in dried blood spots, therefore, provides the basis for a newborn screen for NPC that is ready for piloting in newborn screening programs. ..
  53. Adamec E, Chang H, Stopa E, Hedreen J, Vonsattel J. Tau protein expression in frontotemporal dementias. Neurosci Lett. 2001;315:21-4 pubmed
    ..These findings indicate that the recently reported decreased expression of tau protein in frontotemporal lobe degeneration represents pathogenic mechanism of neurodegeneration detectable only in a special subset of these disorders. ..