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W2895867519 abstract "Core cerebrospinal fluid biomarkers are useful in Alzheimer disease (AD) diagnosis in the general population. Our aim was to study their diagnostic performance in Down syndrome (DS), a population at ultra high risk for AD. We selected a group of individuals with DS without cognitive decline and a group of patients with DS and AD dementia with available baseline lumbar puncture from the prospective longitudinal project Down Alzheimer Barcelona Initiative (DABNI). Participants underwent a comprehensive neurological and neuropsychological evaluation and a lumbar puncture. Diagnosis of AD was made blinded to cerebrospinal fluid biomarkers. Core AD biomarker levels –β-amyloid 1-42 (Aβ1-42) total Tau (tTau) and phosphorilated Tau (pTau)– were determined using ELISA (INNOTEST – Fujirebio Europe, Belgium), ROC analyses were performed based on clinical diagnosis, and optimal cut-offs were obtained (DS cut-offs) from our sample by maximizing the Youden index. We compared the classification of subjects by using DS cut-offs to the classification by using our locally validated cut-off values for general population (GP cut-off) (Aβ1-42= 550pg/mL, Tau= 350pg/mL; pTau= 61pg/mL, Tau/Aβ1-42 ratio = 0.52). Seventy-four subjects with DS were included: 53 without cognitive impairment (mean age 37.2) and 24 with AD dementia (mean age 54.7). The areas under the curve were 0.924 for Aβ1-42, 0.943 for tTau, 0.908 for pTau, and 0.983 for the tTau/Aβ1-42 ratio. GP cut-off values had a sensitivity and specificity of 1 and 0.74 for Aβ1-42, 0.86 and 0.88 for tTau, 0.81 and 0.78 for pTau, and 0.95 and 0.86 for the tTau/Aβ1-42 ratio respectively. DS cut-off values had a sensitivity and specificity of 1 and 0.76 for Aβ1-42, 0.86 and 0.96 for tTau, 0.95 and 0.72 for pTau, and 0.95 and 0.94 for the tTau/Aβ1-42 ratio respectively. When considering abnormal values of Aβ1-42 combined with abnormal tTau levels, GP cut-off correctly classified 66.6% of the sample. The use of calculated DS cut-off values improved the correct classification up to 75%. Cerebrospinal fluid biomarkers are useful for AD diagnosis in DS. General population cut-off values allow an accurate diagnosis of AD in subjects with DS. However, they might need to be adjusted for this population . ROC curves of core cerebrospinal fluid biomarkers in our sample of subjects with Down syndrome. Scatter plot displaying Aβ1-42 and tTau values of subjects with Down syndrome without cognitive impairment (green dots) and with Alzheimer disease dementia. Continuous lines represent the cut-off values of each biomarker in general population. Dotted lines show the cut-off values of each biomarker in our sample of subjects with Down syndrome." @default.
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W2895867519 date "2018-07-01" @default.
W2895867519 modified "2023-10-08" @default.
W2895867519 title "P4‐076: CEREBROSPINAL FLUID CORE BIOMARKERS ALLOW AN ACCURATE DIAGNOSIS OF ALZHEIMER'S DISEASE IN DOWN SYNDROME" @default.
W2895867519 doi "https://doi.org/10.1016/j.jalz.2018.06.2479" @default.
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