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.
References
[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

 
 
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