Article

Cerebrospinal fluid markers for differential dementia diagnosis in a large memory clinic cohort

Departments of Neurology, VU University Medical Center, Alzheimer Center, Amsterdam, The Netherlands.
Neurology (Impact Factor: 8.3). 12/2011; 78(1):47-54. DOI: 10.1212/WNL.0b013e31823ed0f0
Source: PubMed

ABSTRACT To determine how amyloid β 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) levels in CSF behave in a large cohort of patients with different types of dementia.
Baseline CSF was collected from 512 patients with Alzheimer disease (AD) and 272 patients with other types of dementia (OD), 135 patients with a psychiatric disorder (PSY), and 275 patients with subjective memory complaints (SMC). Aβ42, t-tau, and p-tau (at amino acid 181) were measured in CSF by ELISA. Autopsy was obtained in a subgroup of 17 patients.
A correct classification of patients with AD (92%) and patients with OD (66%) was accomplished when CSF Aβ42 and p-tau were combined. Patients with progressive supranuclear palsy had normal CSF biomarker values in 90%. Patients with Creutzfeldt-Jakob disease demonstrated an extremely high CSF t-tau at a relatively normal CSF p-tau. CSF AD biomarker profile was seen in 47% of patients with dementia with Lewy bodies (DLB), 38% in corticobasal degeneration (CBD), and almost 30% in frontotemporal lobar degeneration (FTLD) and vascular dementia (VaD). PSY and SMC patients had normal CSF biomarkers in 91% and 88%. Older patients are more likely to have a CSF AD profile. Concordance between clinical and neuropathologic diagnosis was 85%. CSF markers reflected neuropathology in 94%.
CSF Aβ42, t-tau, and p-tau are useful in differential dementia diagnosis. However, in DLB, FTLD, VaD, and CBD, a substantial group exhibit a CSF AD biomarker profile, which requires more autopsy confirmation in the future.

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    • "Althoughthecutoffvalueoftheratiowasclosetothemean ofthecontrols,specificitywasstillquitehigh,whichmeans therewerestillrelativelyfewfalsepositives.Anexplanation forthiscouldbethatADpatientsshowedalargevariation withinabnormalvalues—mainlyaccountedforbytau values—whereascontrolsweremorecenteredaroundlower normalvalues.Forresearchpurposes,forexampleinclusion intrials,itmightbeusefultoassessamyloidmarkersseparatelyfrominjurymarkers .Ourstudyshowshoweverthat forclinicalpurposes,CSFbiomarkersshouldbecombinedto makeuseoftheircomplementaryvalue. Previously,ithasbeenarguedtousearatiowithtaufor earlydiagnosisofAD,andaratiowithp-tauwouldbe moresuitablefordistinctionfromotherdementias[9] [37]. "
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    • "tration de peptide bêta-amyloı¨de 1-42 est abaissé e au même niveau que dans la MA dans la plupart des e ´ tudes (revue dans (Mukaetova-Ladinska et al., 2010)). La proté ine tau, ré puté e normale dans la DCL (Koopman et al., 2009), est nettement moins discriminante, une sé rie ré cente de cas consé cutifs d'un centre mé moire où plus de la moitié des patients DCL ont des concentrations de proté ine tau phosphorylé e au-dessus du seuil pathologique (Schoonenboom et al., 2012). "
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