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2012 | 72 | 3 |

Tytuł artykułu

Use of cerebrospinal fluid biomarker analysis for improving Alzheimer's disease diagnosis in a non-specialized setting

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
Low levels of amyloid-p42 (Ap42) and high total-tau (t-tau) or phosphorylated-tau (p181-tau) levels in cerebrospinal fluid (CSF) were shown to be characteristic for Alzheimer's disease (AD) patients and for mildly cognitively impaired (MCI) or non-demented individuals who will progress to AD. The goal of this study was to evaluate the benefit of CSF biomarker testing in a setting with no specialized dementia centers, in order to improve the accuracy of AD diagnosis and to identify individuals with incipient AD. Using ELISA assay we analyzed CSF Ap42, t-tau and p181-tau levels among clinically diagnosed non-demented individuals, AD patients and individuals with uncertain dementia (n=36). CSF cut-off values of low Ap42 (<530 pg/mL) and high t-tau (>350 pg/mL) or p181-tau (>52 pg/mL) were used to identify individuals with AD/ MCI-CSF profile, regardless of clinical diagnosis. APOE genotyping was performed using PCR-RFLP method. In accord with previous studies we detected significantly decreased levels of CSF Ap42 and increased tau and p181-tau levels in clinically diagnosed AD group vs. non-demented controls. CSF profiling identified individuals with a typical AD/MCI-CSF pattern in clinically referred non-demented group (9%) and among patients with uncertain dementia (41.7%). APOE e4-allele was associated with the CSF biomarker changes typical for AD. This study shows that in a non-specialized setting CSF biomarker testing may be used as a screening tool for improving the accuracy of AD diagnosis and for predicting individuals with incipient Alzheimer's disease who need to receive further clinical follow-up.

Słowa kluczowe

Wydawca

-

Rocznik

Tom

72

Numer

3

Opis fizyczny

p.264-271,fig.,ref.

Twórcy

autor
  • Division of Molecular Medicine, Ruder Boskovic Institute, Zagreb, Croaltia
autor
  • Division of Molecular Medicine, Ruder Boskovic Institute, Zagreb, Croaltia
autor
  • Department of Neurology, University Hospital Sestre milosrdnice, Zagreb, Croatia
  • Department of Nuclear Medicine and Oncology, University Hospital Sestre milosrdnice, Zagreb, Croatia
autor
  • Department of Neurology, University Hopital Split, Split, Croatia
autor
  • Department of Biology and Medical Genetics, School of Medicine, Univeristy of Rijeka, Rijeka, Croatia
  • Department of Biology and Medical Genetics, School of Medicine, Univeristy of Rijeka, Rijeka, Croatia
autor
  • Department of Neurology, University Hospital Sestre milosrdnice, Zagreb, Croatia
autor
  • Department of Neurology, University Hopital Split, Split, Croatia
autor
  • Department of Neurology, University Hospital Sestre milosrdnice, Zagreb, Croatia
autor
  • Department of Neurology, University Hospital Sestre milosrdnice, Zagreb, Croatia
autor
  • Division of Molecular Medicine, Ruder Boskovic Institute, Zagreb, Croaltia

Bibliografia

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  • Fagan AM, Roe CM, Xiong C, Mintun MA, Morris JC, Holtzman DM (2007) Cerebrospinal fluid tau/beta- amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol 64: 343-349.
  • Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M (2005) Global prevalence of dementia: a Delphi consen¬sus study. Lancet 366: 2112-2117.
  • Folstein MF, Folstein SE, McHugh PR (1975) "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12: 189¬198.
  • Gauthier S, Dubois B, Feldman H, Scheltens P (2008) Revised research diagnostic criteria for Alzheimer's dis¬ease. Lancet Neurol 7: 668-670.
  • Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L (2006) Association between CSF biomark¬ers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol 5: 228-234.
  • Hixson JE, Vernier DT (1990) Restriction isotyping of human apolipoprotein E by gene amplification and cleav¬age with Hhal. J Lipid Res 31: 545-548.
  • Hort J, Bartos A, Pirttila T, Scheltens P (2010) Use of cere¬brospinal fluid biomarkers in diagnosis of dementia across Europe. Eur J Neurol 17: 90-96.
  • Hulstaert F, Blennow K, Ivanoiu A, Schoonderwaldt HC, Riemenschneider M, De Deyn PP, Bancher C, Cras P, Wiltfang J, Mehta PD, Iqbal K, Pottel H, Vanmechelen E, Vanderstichele H (1999) Improved discrimination of AD patients using beta-amyloid(1-42) and tau levels in CSF. Neurology 52: 1555-1562.
  • Mattsson N, Blennow K, Zetterberg H (2010) Inter-laboratory variation in cerebrospinal fluid biomarkers for Alzheimer's disease: united we stand, divided we fall. Clin Chem Lab Med 48: 603-607.
  • Mattsson N, Zetterberg H, Hansson O, Andreasen N, Parnetti L, Jonsson M, Herukka SK, van der Flier WM, Blankenstein MA, Ewers M, Rich K, Kaiser E, Verbeek M, Tsolaki M, Mulugeta E, Rosen E, Aarsland D, Visser PJ, Schroder J, Marcusson J, de LM, Hampel H, Scheltens P, Pirttila T, Wallin A, Jonhagen ME, Minthon L, Winblad B, Blennow K (2009) CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impair¬ment. JAMA 302: 385-393.
  • McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 34: 939-944.
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  • Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16: 1215.
  • Morris JC (2005) Mild cognitive impairment and preclinical Alzheimer's disease. Geriatrics Suppl: 9-14.
  • Riemenschneider M, Lautenschlager N, Wagenpfeil S, Diehl J, Drzezga A, Kurz A (2002) Cerebrospinal fluid tau and beta-amyloid 42 proteins identify Alzheimer disease in subjects with mild cognitive impairment. Arch Neurol 59: 1729-1734.
  • Riemenschneider M, Schmolke M, Lautenschlager N, Guder WG, Vanderstichele H, Vanmechelen E, Kurz A (2000) Cerebrospinal beta-amyloid ((1-42)) in early Alzheimer's disease: association with apolipoprotein E genotype and cognitive decline. Neurosci Lett 284: 85-88.
  • Saunders AM, Strittmatter WJ, Schmechel D, George- Hyslop PH, Pericak-Vance MA, Joo SH, Rosi BL, Gusella JF, Crapper-MacLachlan DR, Alberts MJ (1993) Association of apolipoprotein E allele epsilon 4 with late- onset familial and sporadic Alzheimer's disease. Neurology 43: 1467-1472.
  • Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR, Jr., Kaye J, Montine TJ, Park DC, Reiman EM, Rowe CC, Siemers E, Stern Y, Yaffe K, Carrillo MC, Thies B, Morrison-Bogorad M, Wagster MV, Phelps CH (2011) Toward defining the pre¬clinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 7: 280-292.
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Bibliografia

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