Abstract
The clinical features and recent developments in the neuropathology of frontotemporal dementia are reviewed. The five main neurodegenerative disorders that underlie the clinical syndrome of frontotemporal dementia are distinguished using immunohistochemistry with antisera to ubiquitin and tau proteins. Motor neuron disease-type dementia is characterised by ubiquitin-immunoreactive intraneuronal inclusions in cortical layer II and the hippocampal dentate granule cells. A diagnosis of Alzheimer’s disease changes is based upon the presence of neurofibrillary tangles, which immunostain with antibodies to tau and ubiquitin, and many associated neuritic plaques. Corticobasal degeneration is diagnosed by the presence of tau-immunoreactive, but ubiquitin-non-reactive intraneuronal inclusions in cortical layer II and the substantia nigra. Pick’s disease is restricted to cases with tau- and ubiquitin-immunoreactive spherical cortical intraneuronal inclusions (Pick bodies), best seen in the hippocampal dentate gyrus and frontotemporal cortex. Dementia of frontal type is the preferred term for cases in which no intraneuronal inclusions are seen with antisera to tau and ubiquitin. A practical approach to the pathological diagnosis of frontotemporal dementia and the differential diagnosis of the five disorders using immunohistochemical studies is provided.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Akelatis AJ (1944) Atrophy of basal ganglia in Pick’s disease. Arch Neurol Psychiatry 51: 27–34
Brun A (1987) Frontal lobe degeneration of non-Alzheimer type. 1. Neuropathology. Arch Gerentol Geriatr 6: 193–207
Clarke AW, Manz HJ, White CL, Lehmann J, Miller D, Coyle JT (1986) Cortical degeneration with swollen chromatolytic neurons: its relationship to Pick’s disease. J Neuropathol Exp Neurol 45: 268–284
Constantinidis J, Richard J, Tissot R (1974) Pick’s disease: histological and clinical correlations. Eur Neurol 11: 208–217
Cooper PN, Jackson M, Lennox G, Lowe J, Mann DMA (1995) Tau, ubiquitin and aB crystallin immunohistochemistry define the principal causes of degenerative frontotemporal dementia. Arch Neurol 52: 1011–1015
Dickson DW. Yen S-H, Suzuki KI, et al (1986) Ballooned neurons in select neurodegenerative diseases contain phosphorylated neurofilament epitopes. Acta Neuropathol (Berl) 71: 216–223
Feany MB, Ksiezak-Reding H, Liu W-K, et al (1995) Epitope expression and hyperphosphorylation of tau protein in corticobasal degeneration: differentiation from progressive supranuclear palsy. Acta Neuropathol 90: 37–43
Giannakopoulos P, Hof PR, Bouras C (1995) Dementia lacking distinctive histopathology: clinicopathological evauation of 32 cases. Acta Neuropathol 89: 346–355
Gibb WRG, Luthert PJ, Marsden CD (1989) Corticobasal degeneration. Brain 112: 1171–1192
Gustafson L (1987) Frontal lobe degeneration of non-Alzheimer-type. II. Clinical picture and differential diagnosis. Arch Gerontol Geriatr 6: 209–223
Higuchi Y, Iwaki T, Tateishi J (1995) Neurodegeneration in limbic and paralimbic system in progressive supranuclear palsy. Neuropathol Appl Neurobiol 21: 246–254
Hori A, Voiles E, Witzke R, Spaar FW (1987) Pick’s disease of early onset with neurologic symptomatology, rapid course and nigrostriatal degeneration. Clin Neuropathol 2: 8–15
Jackson M, Lennox G, Ward L, Lowe J (1995) Frontal dementia with MND inclusions without clinical ALS: report of eleven cases. Neuropathol Appl Neurobiol 21: 148–149
Kew J, Leigh N (1992) Dementia with motor neurone disease. Baillieres Clin Neurol 1: 611–626
Knopman DS, Mastri AR, Frey WH, et al (1990) Dementia lacking distinctive histological features: a common non-Alzheimer degenerative dementia. Neurology 40: 251–266
Lang AE, Riley DE, Bergeron C (1994) Cortical-basal ganglionic degeneration. In: Calne DB (ed) Neurodegenerative diseases. Saunders, Philadelphia, pp 877–894
Lanska DJ, Currier RD, Cohen M, et al (1994) Familial progressive subcortical gliosis. Neurology 44: 1633–1643
Lantos PL (1990) Ageing and dementias. In: Weller RO (ed) Nervous system, muscle and eyes; systemic pathology, 3rd edn, vol 4. Churchill Livingstone, Edinburgh, pp 360–396
Lantos PL (1992) Neuropathology of unusual dementias: an overview. Baillieres Clin Neurol 1: 485–516
Lassmann H, Weiler R, Fischer P, et al (1992) Synaptic pathology in Alzheimer’s disease: immunological data for markers of synaptic and large dense-core vesicles. Neuroscience 46: 1–8
Lennox G, Jackson M, Lowe J (1994) Corticobasal degeneration manifesting as as a frontal lobe syndrome without movement disorder. Neuropathol Appl Neurobiol 20: 514
Lowe J, Ellington JR, Lennox G, et al (1992) Ballooned neurons in several neurodegenerative diseases and stroke contain aB crystallin. Neuropathol Appl Neurobiol 18: 341–350
Mann DMA, South PW, Snowden JS, Neary D (1993) Dementia of frontal type: neuropathology and immunohistochemistry. J Neurol Neurosurg Psychiatry 56: 605–614
Murayama S, Mori H, Ihara Y, Tomonaga M (1990) Immunocytological and ultrastructural studies of Pick’s disease. Ann Neurol 27: 394–405
Neary D, Snowden JS, Shields RA, et al (1987) Single photon emission tomography using 99 mTc-HM-PAO in the investigation of dementia. J Neurol Neurosurg Psychiatry 50:1101–1109
Neary D, Snowden JS, Northern B, Goulding PJ (1988) Dementia of frontal lobe type. J Neurol Neurosurg Psychiatry 51: 353–361
Neumann MA, Cohn R (1967) Progressive subcortical gliosis, a rare form of pre-senile dementia. Brain 90: 405–427
Okamoto K, Hirai S, Yamazaki Y, Sun X, Nakazato Y (1991) New ubiquitin-positive intraneuronal inclusions in the extramotor cortices in patients with amyotrophic lateral sclerosis. Neurosci Lett 129: 233–236
Petersen RB, Tabaton M, Chen SG, et al (1995) Familial progressive subcortical gliosis. Presence of prions and linkage to chromosome 17. Neurology 45: 1062–1067
Pollanen MS, Bergeron C, Weyer L (1993) Absence of protease-resistant prion protein in dementia characterised by neuronal loss and status spongiosus. Acta Neuropathol 86: 515–517
Riley DE, Lang AE, Lewis A, et al (1990) Cortical-basal ganglionic degeneration. Neurology 40: 1203–1212
The Lund group and the Manchester groups (1994) Consensus on clinical and neuropathological criteria for frontotemporal dementia. J Neurol Neurosurg Psychiatry 57: 416–418
Uchihara T, Mitani K, Mori H, et al (1994) Abnormal cytoskeletal pathology peculiar to corticobasal degeneration is different from that of Alzheimer’s disease or progressive supranuclear palsy. Acta Neuropathol 88: 379–383
Van Mansvelt J (1954) Pick’s disease: a syndrome of lobar cerebral atrophy: clinicoanatomical and histopathological studies. Doctoral dissertation, Universityof Utrecht
Verity A, Wechsler AF (1987) Progressive subcortical gliosis of Neumann: a clinicopathologic study of two cases with review. Arch Gerontol Geriatr 6: 245–261
Wakabayashi K, Oyanagi K, Makifuchi T, et al (1994) Corticobasal degeneration: etiopathological significance of the cytoskeletal alterations. Acta Neuropathol 87: 545–553
Wightman G, Anderson VER, Martin J, et al (1992) Hippocampal and neocortical ubiquitin immunoreactive inclusions in amyotrophic lateral sclerosis with dementia. Neurosci Lett 139: 269–274
Winkelman NW, Book MH (1949) Asymptomatic extrapyramidal involvement in Pick’s disease: a clinicopathological study of cases. J Neuropathol Exp Neurol 8: 30–42
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Jackson, M., Lowe, J. The new neuropathology of degenerative frontotemporal dementias. Acta Neuropathol 91, 127–134 (1996). https://doi.org/10.1007/s004010050403
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s004010050403