AAD  Vol.1 No.3 , December 2012
Prevalence of cerebrospinal fluid Alzheimer disease-like pattern in atypical dementias
Abstract: BACKGROUND: Differential diagnosis between Frontotemporal Dementia (FTD), Corticobasal Syndrome (CBS), Progressive Supranuclear Palsy Syndrome (PSP), FTD with motor neuron disease (FTD-MND) is often challenging, because of the occurrence of atypical cases. Autopsy series have identified Alzheimer Disease (AD) pathology in a consistent percentage of patients with atypical dementias. It has been demonstrated that Cerebrospinal Fluid (CSF) Tau/Aβ42 dosage is a reliable marker for AD. OBJECTIVE: To evaluate the presence and percentage of CSF AD-like patterns (high CSF tau/Aβ42 ratio) in patients with atypical dementias in order to identify an ongoing AD neurodegenerative process. METHODS: One hundred seventy two consecutive patients fulfilling current clinical criteria for behavioural variant FTD (bvFTD, n = 73), agrammatic variant of Primary Progressive Aphasia (avPPA, n = 19), semantic variant of PPA (svPPA, n = 12), FTD-MND (n = 5), CBS (n = 42), PSP (n = 21) were recruited and underwent CSF analysis. CSF AD-like and non AD (nAD-like) patterns were identified. RESULTS: CSF AD-like pattern was reported in 6 out of 73 cases (8.2%) in the bvFTD group, in 3 out of 19 (15.8%) in the avPPA group, and in 7 out of 42 (16.7%) in the CBS group. One out of 12 (8.3%) of svPPA had CSF AD-like pattern. None of patients FTD-MND and PSP had CSF AD-like pattern. No differences in demographic characteristics were detected between subgroups in each phenotype. CONCLUSIONS: Our findings convey that the CSF tau/ Aβ42 ratio could be found in a proportion of cases with clinical bvFTD, avPPA and CBD. Detecting anon-going AD pathological process in atypical dementias has several implications for defining distinctive therapeutic approaches, guiding genetic screening and helping in patients’ selection in future clinical trials.
Cite this paper: Padovani, A., Benussi, A., Ferrari, F., Archetti, S. and Borroni, B. (2012) Prevalence of cerebrospinal fluid Alzheimer disease-like pattern in atypical dementias. Advances in Alzheimer's Disease, 1, 45-50. doi: 10.4236/aad.2012.13006.

[1]   Rohrer, J.D., Lashley, T., Schott, J.M., et al. (2011) Clinical and neuroanatomical signatures of tissue pathology in frontotemporal lobar degeneration. Brain, 134, 2565-2581. doi:10.1093/brain/awr198

[2]   Rascovsky, K., Hodges, J.R., Knopman, D., et al. (2011) Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain, 134, 2456-2477. doi:10.1093/brain/awr179

[3]   Lopez, O.L., Becker, J.T., Klunk, W., et al. (2000) Research evaluation and diagnosis of probable Alzheimer’s disease over the last two decades: I. Neurology, 55, 1854- 1862. doi:10.1212/WNL.55.12.1854

[4]   Cummings, J.L. (2000) Cognitive and behavioral heterogeneity in Alzheimer’s disease: Seeking the neurobiological basis. Neurobiology of Aging, 21, 845-861. doi:10.1016/S0197-4580(00)00183-4

[5]   Kertesz, A., McMonagle, P., Blair, M., et al. (2005) The evolution and pathology of frontotemporal dementia. Brain, 128, 1996-2005. doi:10.1093/brain/awh598

[6]   Forman, M.S., Farmer, J., Johnson, J.K., et al. (2006) Frontotemporal dementia: Clinicopathological correlations. Annals of Neurology, 59, 952-962. doi:10.1002/ana.20873

[7]   Visser, P.J., Verhey, F., Knol, D.L., et al. (2009) Prevalence and prognostic value of CSF markers of Alzheimer’s disease pathology in patients with subjective cognitive impairment or mild cognitive impairment in the DESCRIPA study: A prospective cohort study. The Lancet Neurology, 8, 619-627. doi:10.1016/S1474-4422(09)70139-5

[8]   Mattsson, N., Zetterberg, H., Hansson, O., et al. (2009) CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. The Journal of the American Medical Association, 302, 385-393. doi:10.1001/jama.2009.1064

[9]   Tapiola, T., Alafuzoff, I., Herukka, S.-K., et al. (2009) Cerebrospinal fluid {beta}-amyloid 42 and tau proteins as biomarkers of Alzheimer-type pathologic changes in the brain. Archives of Neurology, 66, 382-389. doi:10.1001/archneurol.2008.596

[10]   Premi, E., Garibotto, V., Alberici, A., et al. (2012) Nature versus nurture in frontotemporal lobar degeneration: the interaction of genetic background and education on brain damage. Dementia and Geriatric Cognitive Disorders, 33, 372-378. doi:10.1159/000339366

[11]   Bian, H., Van Swieten, J.C., Leight, S., et al. (2008) CSF biomarkers in frontotemporal lobar degeneration with known pathology. Neurology, 70, 1827-1835.

[12]   Seelaar, H., Rohrer, J.D., Pijnenburg, Y.A.L., et al. (2011) Clinical, genetic and pathological heterogeneity of frontotemporal dementia: A review. Journal of Neurology, Neurosurgery & Psychiatry, 82, 476-486. doi:10.1136/jnnp.2010.212225

[13]   Davies, R.R., Hodges, J.R., Kril, J.J., et al. (2005) The pathological basis of semantic dementia. Brain, 128, 1984- 1995. doi:10.1093/brain/awh582

[14]   Grossman, M. (2010) Primary progressive aphasia: Clinicopathological correlations. Nature Reviews. Neurology, 6, 88-97. doi:10.1038/nrneurol.2009.216

[15]   Mesulam, M., Wicklund, A., Johnson, N., et al. (2008) Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia. Annals of Neurology, 63, 709- 719. doi:10.1002/ana.21388

[16]   Deramecourt, V., Lebert, F., Debachy, B., et al. (2010) Prediction of pathology in primary progressive language and speech disorders. Neurology, 74, 42-49. doi:10.1212/WNL.0b013e3181c7198e

[17]   Cairns, N.J., Bigio, E.H., Mackenzie, I.R., et al. (2007) Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: Consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathologica, 114, 5-22. doi:10.1007/s00401-007-0237-2

[18]   Sampathu, D.M., Neumann, M., Kwong, L.K., et al. (2006) Pathological heterogeneity of frontotemporal lobar degeneration with ubiquitin-positive inclusions delineated by ubiquitin immunohistochemistry and novel monoclonal antibodies. The American Journal of Pathology, 169, 1343-1352. doi:10.2353/ajpath.2006.060438

[19]   Verwey, N.A., Kester, M.I., van der Flier, W.M., et al. (2010) Additional value of CSF amyloid-beta 40 levels in the differentiation between FTLD and control subjects. Journal of Alzheimer’s Disease, 20, 445-452.

[20]   Urakami, K., Wada, K., Arai, H., et al. (2001) Diagnostic significance of tau protein in cerebrospinal fluid from patients with corticobasal degeneration or progressive supranuclear palsy. Journal of the Neurological Sciences, 183, 95-98. doi:10.1016/S0022-510X(00)00480-9

[21]   Paraskevas, G.P. (2005) The diagnostic value of cerebrospinal fluid tau protein in sementing and nondementing neuropsychiatric disorders. Journal of Geriatric Psychiatry and Neurology, 18, 163-173. doi:10.1177/0891988705277549

[22]   Arai, H., Morikawa, Y., Higuchi, M., et al. (1997) Cerebrospinal fluid tau levels in neurodegenerative diseases with distinct tau-related pathology. Biochemical and Biophysical Research Communications, 236, 262-264. doi:10.1006/bbrc.1997.6908

[23]   Noguchi, M., Yoshita, M., Matsumoto, Y., et al. (2005) Decreased beta-amyloid peptide42 in cerebrospinal fluid of patients with progressive supranuclear palsy and corticobasal degeneration. Journal of the Neurological Sciences, 237, 61-65. doi:10.1016/j.jns.2005.05.015

[24]   Sha, S., Hou, C., Viskontas, I.V., et al. (2006) Are frontotemporal lobar degeneration, progressive supranuclear palsy and corticobasal degeneration distinct diseases? Nature Clinical Practice. Neurology, 2, 658-665. doi:10.1038/ncpneuro0357

[25]   Chand, P., Grafman, J., Dickson, D., et al. (2006) Alzheimer’s disease presenting as corticobasal syndrome. Movement Disorders, 21, 2018-2022. doi:10.1002/mds.21055

[26]   Boeve, B.F., Lang, A.E. and Litvan, I. (2003) Corticobasal degeneration and its relationship to progressive supranuclear palsy and frontotemporal dementia. Annals of Neurology, 54, S15-S19. doi:10.1002/ana.10570

[27]   Lang, A.E. (2003) Corticobasal degeneration: Selected developments. Movement Disorders, 18, S51-S56. doi:10.1002/mds.10563

[28]   Dickson, D.W. (2012) Parkinson’s disease and parkinsonism: Neuropathology. Cold Spring Harbor Perspectives in Medicine, 2, a009258.

[29]   Borroni, B., Malinverno, M., Gardoni,F., et al. (2008) Tau forms in CSF as a reliable biomarker for progressive supranuclear palsy. Neurology, 71, 1796-1803. doi:10.1212/01.wnl.0000335941.68602.39

[30]   Dubois, B., Feldman, H.H., Jacova, C., et al. (2007) Research criteria for the diagnosis of Alzheimer’s disease: Revising the NINCDS-ADRDA criteria. The Lancet Neurology, 6, 734-746. doi:10.1016/S1474-4422(07)70178-3

[31]   Hu, W.T., Rippon, G.W., Boeve, B.F., et al. (2009) Alzheimer’s disease and corticobasal degeneration presenting as corticobasal syndrome. Movement Disorders, 24, 1375- 1379. doi:10.1002/mds.22574

[32]   Grossman, M., Libon, D.J., Forman, M.S., et al. (2007) Distinct antemortem profiles in patients with pathologically defined frontotemporal dementia. Archives of Neurology, 64, 1601-1609. doi:10.1001/archneur.64.11.1601

[33]   Jellinger, K.A. and Attems, J. (2010) Prevalence of dementia disorders in the oldest-old: An autopsy study. Acta Neuropathology, 119, 421-433. doi:10.1007/s00401-010-0654-5

[34]   Cohen, A.D., Rabinovici, G.D., Mathis, C.A., et al. (2012) Using pittsburgh compound B for in vivo PET imaging of fibrillar amyloid-beta. Advances in Pharmacology, 64, 27-81. doi:10.1016/B978-0-12-394816-8.00002-7