Skip to main content
NCBI home page
Brain Pathology logoLink to Brain Pathology
. 2006 Apr 5;8(2):377–386. doi: 10.1111/j.1750-3639.1998.tb00161.x

Dementia with Grains (Argyrophilic Grain Disease)

Kurt A Jellinger 1,✉
PMCID: PMC8098394  PMID: 9546294

Abstract

Dementia with grains, also referred to as argyrophilic grain disease, is a morphological condition in elderly individuals histologically characterised by the widespread occurrence of minute, spindle or comma‐shaped argyrophilic, tau‐immunoreactive structures distinct from neuropil threads that are predominantly located in the hippocampus and related limbic areas including the amygdala. They are suggested to arise mainly in dendrites of neurons showing accumulation of hyperphosphorylated tau proteins (pretangle stage) but not necessarily forming paired helical filaments. Argyrophilic grains are associated with argyrophilic, tau‐positive oligodendroglial inclusions (“coiled bodies”) in the white matter, while astroglia are not affected. Argyrophilic grain disease is considered to be a progressive disorder that may or may not be associated with dementia, the grains occasionally being the only morphologic substrates of cognitive decline. They often occur in combination with neuritic Alzheimer‐type lesions (many corresponding to “limbic” Braak stages III and IV) or other neurodegenerative disorders, such as progressive supranuclear palsy, corticobasal degeneration, or Pick's disease. The prevalence and pathogenesis of this condition, its clinicopathologic correlations and nosological position among tau‐pathology related disorders await further elucidation.

Full Text

The Full Text of this article is available as a PDF (237.6 KB).

References

  • 1. Arima K, Murayama S, Mukoyama M, Inose T (1992) Immunocytochemical and ultratrastructural studies of neuronal and oligodendroglial cytoplasmic inclusions in multiple system atrophy. 1. Neuronal cytoplasmic inclusions. Acta Neuropathol 83: 453–460. [DOI] [PubMed] [Google Scholar]
  • 2. Arima K, Nakamura M, Sunohara N, Ogawa M, Anno M, Izumiyama Y, Horai S, Ikeda K (1997) Ultrastructural characterization of the tau‐immunoreactive tubules in the oligodendroglial perikarya and their inner loop processes in progressive supranuclear palsy. Acta Neuropathol 93: 558–566. [DOI] [PubMed] [Google Scholar]
  • 3. Bancher C, Brunner C, Lassmann H, Budka H, Jellinger K, Wiche G, Seitelberger F, Grundke‐Iqbal I, Iqbal K, Wisniewski HM (1989) Accumulation of abnormally phosphorylated tau precedes the formation of neurofibrillary tangles in Alzheimer's disease. Brain Res 477: 90–99. [DOI] [PubMed] [Google Scholar]
  • 4. Bergeron C, Pollanen MS, Weyer L, Lang AE (1997) Cortical degeneration in progressive supranuclear palsy. A comparison with cortical‐basal ganglionic degeneration. J Neuropathol Exp Neurol 56: 726–734. [PubMed] [Google Scholar]
  • 5. Braak H, Braak E (1987) Argyrophilic grains: characteristic pathology of cerebral cortex in cases of adult onset dementia without Alzheimer changes. Neurosci Lett 76: 124–27. [DOI] [PubMed] [Google Scholar]
  • 6. Braak H, Braak E (1989) Cortical and subcortical argyrophilic grains characterize a disease associated with adult onset dementia. Neuropathol Appl Neurobiol 15: 13–26. [DOI] [PubMed] [Google Scholar]
  • 7. Braak H, Braak E (1991) Neuropathological stageing of Alzheimer‐related changes. Acta Neuropathol 82: 239–259. [DOI] [PubMed] [Google Scholar]
  • 7a. Braak H, Braak E (1998) Argyrophilic grain disease: Frequency of occurence in different age categories and neuropathological diagnostic criteria. J Neural Transm (in press). [DOI] [PubMed] [Google Scholar]
  • 8. Braak H, Braak E, Mandelkow EM (1994) A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads. Acta Neuropathol 87: 554–567. [DOI] [PubMed] [Google Scholar]
  • 9. Buée‐Scherrer V, Hof PR, Buée L, et al. (1996) Hyperphosphorylated tau proteins differentiate corticobasal degeneration and Pick's disease. Acta Neuropathol 91: 351–359. [DOI] [PubMed] [Google Scholar]
  • 10. Carmel G, Mager EM, Binder LI, Kuret J (1996) The structural basis of monoclonal antibody Alz50′s selectivity for Alzheimer's disease pathology. J Biol Chem 271: 32789–32795. [DOI] [PubMed] [Google Scholar]
  • 11. Chin SS, Goldman JE (1996) Glial inclusions in CNS degenerative diseases. J Neuropathol Exp Neurol 55: 499–508. [DOI] [PubMed] [Google Scholar]
  • 12. Cras P, Perry G (1991) Dementia with argyrophilic grains. Ann Neurol 30: 853–854. [DOI] [PubMed] [Google Scholar]
  • 13. Davis DG, Ross GW, Petrovitch H, White LR, Hardman JM, Nelson JS, Thiessen P, Wang HZ, Patel E, Marsebery WR (1997) Quantitation of argyrophilic grains in hippocampal CA‐1 of aged Japanese‐American men (abstr.). J Neuropathol Exp Neurol 56: 587. [Google Scholar]
  • 14. Dickson DW (1997) Neurodegenerative diseases with cytoskeletal pathology: A biochemical classification. Ann Neurol 42: 541–544. [DOI] [PubMed] [Google Scholar]
  • 15. Dickson DW, Crystal HA, Mattiace LA, Masur DM, Blau AD, Davies P, Yen SM, Aronson M N (1991) Identification of normal and pathological aging in prospectively studied nondemented elderly humans. Neurobiol Aging 13: 179–189. [DOI] [PubMed] [Google Scholar]
  • 16. Feany MB, Dickson DW (1995) Widespread cytoskeletal pathology characterizes corticobasal degeneration. Am J Pathol 146: 1388–1396. [PMC free article] [PubMed] [Google Scholar]
  • 17. Feany MB, Dickson DW (1996) Neurodegenerative disorders with extensive tau pathology: a comparative study and review. Ann Neurol 40: 139–148. [DOI] [PubMed] [Google Scholar]
  • 18. Feany MB, Ksiezak‐Reding H, Liu W‐K, Vincent I, Yen SHC, Dickson DW (1995) Epitope expression and hyperphosphorylation of tau protein in corticobasal degeneration; differentiation from progressive supranuclear palsy. Acta Neuropathol 90: 37–43. [DOI] [PubMed] [Google Scholar]
  • 19. Feany MB, Mattiace LA, Dickson DW (1996) Neuropathologic overlap of progressive supranuclear palsy, Pick's disease, and corticobasal degeneration. J Neuropathol Exp Neurol 55: 53–67. [DOI] [PubMed] [Google Scholar]
  • 20. Ferrer I, Guionnet N, Cruz‐Sánchez F, Tuñón T (1990) Neuronal alterations in patients with dementia: a Golgi study on biopsy samples. Neurosci Lett 114: 11–16. [DOI] [PubMed] [Google Scholar]
  • 21. Flament S, Delacourte A, Verny M, et al. (1991) Abnormal tau proteins in progressive supranuclear palsy. Similarities and differences with the neurofibrillary degeneration of the Alzheimer type. Acta Neuropathol 81: 591–596. [DOI] [PubMed] [Google Scholar]
  • 22. Gallyas F (1971) Silver staining of Alzheimer's neurofibrillary changes by means of physical development. Acta Morph Acad Sci Hung 19: 1–8. [PubMed] [Google Scholar]
  • 23. Ikeda K, Akiyama H, Haga C, Kondo H, Arima K, Oda T (1994) Argyrophilic thread‐like structure in corticobasal degeneration and supranuclear palsy. Neurosci Lett 174: 157–159. [DOI] [PubMed] [Google Scholar]
  • 24. Ikeda K, Akiyama H, Kondo H, Arai T, Arai N, Yagishita S (1995) Numerous glial fibrillary tangles in oligodendroglia in cases of subacute sclerosing panencephalitis with neurofibrillary tangles. Neurosci Lett 194: 133–35. [DOI] [PubMed] [Google Scholar]
  • 25. Ikeda K, Akiyama H, Kondo H, Haga C (1995) A study of dementia with argyrophilic grains. Possible cytoskeletal abnormality in dendrospinal portion of neurons and oligodendroglia. Acta Neuropathol 89: 409–414. [DOI] [PubMed] [Google Scholar]
  • 26. Itagaki S, McGeer PL, Akiyama H, Beattie BL, Walker DG, Moore GRW, McGeer EG (1989) A case of adult‐onset dementia with argyrophilic grains. Ann Neurol 26: 685–689. [DOI] [PubMed] [Google Scholar]
  • 27. Iwatsubo T, Hasegawa M, Ihara Y (1994) Neuronal and glial tau‐positive inclusions in diverse neurologic diseases share common phosphorylation characteristics. Acta Neuropathol 88:129–136. [DOI] [PubMed] [Google Scholar]
  • 28. Jellinger, KA , Bancher C (1998) Senile dementia with tangles (Tangle predominant form of senile dementia). Brain Pathol 8 (in press). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29. Komori T, Arai N, Oda M, Nakayama H, Murayama S, Amano N, Shibata N, Kobayashi M, Sasaki S (1997) Morphologic difference of neuropil threads in Alzheimer's disease, corticobasal degeneration and progressive supranuclear palsy: a morphometric study. Neurosci Lett 233: 89–92. [DOI] [PubMed] [Google Scholar]
  • 30. Komori T, Arai N, Oda M, Nakayama H, Mori H, Yagishita S, Takahashi T, Amano N, Murayama S, Murakami S, Shibata N, Kobayashi M, Sasaki S, Iwata M (1998) Astrocytic plaques and tufts of abnormal fibers do not coexist in corticobasal degeneration and progressive supranuclear palsy. Acta Neuropathol (in press). [DOI] [PubMed] [Google Scholar]
  • 31. Ksiezak‐Reding H, Tracz E, Yang L‐S, Dickson DW, Simon M, Walls JS (1996) Ultrastructural instability of paired helical filaments from corticobasal degeneration as examined by scanning transmission electron microscopy. Am J Pathol 149: 639–651. [PMC free article] [PubMed] [Google Scholar]
  • 32. Martinez‐Lage P, Munoz DG (1997) Prevalence of diseases associated with argyrophilic grains of Braak. J Neuropathol Exp Neurol 56: 157–164. [DOI] [PubMed] [Google Scholar]
  • 33. Masliah E, Hansen LA, Quijata S, DeTeresa R, Alford M, Kauss J, Terry R (1991) Late onset dementia with argyrophilic grains and subcortical tangles or atypical progressive supranuclear palsy Ann Neurol 29: 389–96. [DOI] [PubMed] [Google Scholar]
  • 34. Matsumoto S, Udaka F, Kameyama M, et al. (1996) Subcortical neurofibrillary tangles, neuropil threads, and argentophilic glial inclusions in corticobasal degeneration. Clin Neuropathol 15: 209–214. [PubMed] [Google Scholar]
  • 35. Mattiace L, Wu E, Aronson M, Dickson D (1991) A new type of neuritic plaque without amyloid in corticonigral degeneration with neuronal achromasia (abstract). J Neuropathol Exp Neurol 50: 310. [Google Scholar]
  • 36. Nishimura M, Tomimoto H, Suenaga T, Namba Y, Ikeda K, Akiguchi I, Kimura J (1995) Immunocytochemical characterization of glial fibrillary tangles in Alzheimer's disease brain. Am J Pathol 146:1052–1058. [PMC free article] [PubMed] [Google Scholar]
  • 37. Papp MI, Lantos PL (1994) The distribution of oligodendroglial inclusions in multiple system atrophy and its relevance to clinical symptomatology. Brain 117: 235–243. [DOI] [PubMed] [Google Scholar]
  • 38. Pollanen MS, Markiewicz P, Goh Cynthia (1997) Paired helical filaments are twisted ribbons composed of two parallel and aligned components. Image reconstruction and modelling of filament structure using atomic force microscopy. J Neuropathol Exp Neurol 56: 79–85. [DOI] [PubMed] [Google Scholar]
  • 39. Probst A, Basler V, Bron B, Ulrich J (1983) Neuritic plaques in senile dementia of Alzheimer type: a Golgi analysis in the hippocampal region. Brain Res 268: 249–254. [DOI] [PubMed] [Google Scholar]
  • 40. Probst A, Langui, D , Lautenschlager C, Ulrich J, Brion JP, Anderton BH (1988) Progressive supranuclear palsy: extensive neuropil threads in addition to neurofibrillary tangles: very antigenicity of subcortical neuronal pathology in progressive supranuclear palsy and Alzheimer's disease. Acta Neuropathol 77: 61–68. [DOI] [PubMed] [Google Scholar]
  • 41. Seubert P, Mawal‐Dewan M, Barbour R, Jakes R, Goedert M, Johnson GVM, Literski JM, Schenk D, Lieberburg I, Trojanowski JQ, Lee VM‐Y (1995) Detection of phosphorylated Ser 262 in fetal tau, adult tau and paired helical filament‐tau. J Biol Chem 270: 18917–18922. [DOI] [PubMed] [Google Scholar]
  • 42. Takahashi T, Amano N, Hanihara T et al. (1996) Corticobasal degeneration widespread argentophilic threads and glia in addition to neurofibrillary tangles. Similarities of cytoskeletal abnormalities in corticobasal degeneration and progressive supranuclear palsy. J Neurol Sci 138: 66–77. [DOI] [PubMed] [Google Scholar]
  • 43. Tolnay M, Spillantini MG, Goedert M, Ulrich J, Langui D, Probst A (1997) Argyrophilic grain disease: widespread hyperphosphorylation of tau protein in limbic neurons. Acta Neuropathol 93: 477–484. [DOI] [PubMed] [Google Scholar]
  • 44. Tolnay M, Schwietert M, Monsch AU, Stihelin H, Langui D, Probst A (1997) Argyrophilic grain disease: distribution of grains in patients with and without dementia. Acta Neuropathol 94: 353–358. [DOI] [PubMed] [Google Scholar]
  • 45. Tolnay M, Ipsen S, Mistl C, Probst A (1997) Argyrophilic grain disease: occurrence of grains inside dendritic branches of neurons containing hyperphosphorylated tau protein (abstr.). Brain Pathol 7: 1176. [Google Scholar]
  • 46. Tolnay M, Mistl C, Ipsen S, Probst A (1998) Argyrophilic grains of Braak: occurrence in dendrites of neurons containing hyperphosphorylated tau protein. Neuropathol Appl Neurobiol (in press). [DOI] [PubMed] [Google Scholar]
  • 47. Ulrich J, Spillantini MG, Goedert M, Dukas L, Stähelin HB (1992) Abundant neurofibrillary tangles without senile plaques in a subset of patients with senile dementia. Neurodegeneration 1:257–284. [Google Scholar]
  • 48. Wakabayashi K, Oyanagi K, Makifuchi T, Ikuta F, Homma A, Homma Y, Horikawa Y, Tokiguchi S (1994) Corticobasal degeneration: etiopathological significance of the cytoskeletal alterations. Acta Neuropathol 87: 545–553. [DOI] [PubMed] [Google Scholar]
  • 49. Wenning GK, Jellinger K, Litvan I (1997) Supranuclear gaze palsy and eyelid apraxia in postencephalitic parkinsonism. J Neural Transm 104: 845–865. [DOI] [PubMed] [Google Scholar]
  • 50. Yamada T, McGeer PL (1990) Oligodendroglial microtubular masses: an abnormality observed in some human neurodegenerative diseases. Neurosci Lett 120: 163–166. [DOI] [PubMed] [Google Scholar]
  • 51. Yamada T, McGeer PL, McGeer EG (1992) Some immunohistochemical features of argyrophilic grain dementia with normal cortical choline acetyltransferase levels but extensive subcortical pathology and markedly reduced dopamine. J Geriatr Psychiatry Neurol 5: 3–13. [DOI] [PubMed] [Google Scholar]
  • 52. Yamaguchi H, Nakazato Y, Shoji M, Ihara Y, Hirai S (1990) Ultrastructure of the neuropil threads in the Alzheimer brain: their dendritic origin and accumulation in the senile plaques. Acta Neuropathol 80: 368–374. [DOI] [PubMed] [Google Scholar]
  • 53. Yamazaki M, Nakano I, Imazu O, Terashi A (1995) Paired helical filaments and straight tubules in astrocytes: an electron microscopic study in dementia of the Alzheimer type. Acta Neuropathol 90: 51–56. [DOI] [PubMed] [Google Scholar]

Articles from Brain Pathology are provided here courtesy of Wiley

RESOURCES