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P1‐113: Influence of AD pathology on CSF biomarkers in autopsy‐confirmed Dementia with Lewy Bodies patients

Alzheimers & Dementia(2011)

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Abstract
The neuropathological hallmark for dementia with Lewy Bodies (DLB) is the presence of Lewy bodies. Besides Lewy bodies, DLB patients often show Alzheimer's disease (AD) type pathology like senile plaques (SP) and neurofibrillary tangles (NFT). Three frequently used AD-biomarkers in cerebrospinal fluid (CSF) for AD are amyloid-beta (Aß1-42), total tau (T-tau) and phoshporylated tau (P-tau181P). In DLB patients, the biomarker profiles are in-between the profiles of AD patients and healthy subjects which might be a result of AD pathology in some DLB patients. To test this hypothesis, we set up a study aiming to investigate the influence of AD pathology on the CSF biomarker profile of DLB patients. The degree of AD pathology was determined through assessment of Braak's NFT and SP stages in 18 neuropathologically confirmed DLB patients. The CSF biomarkers Aß1-42, T-tau and P-tau181P were analyzed by means of single-parameter ELISA kits. Biomarker analyses were performed in CSF samples of 30 neuropathologically confirmed AD patients too (control group). DLB patients without SP had a higher CSF Aß1-42 concentrations than DLB patients with SP (Mann-Whitney U: p = 0.034) and AD patients (p = 0.006). DLB patients with senile plaques could be discriminated from DLB patients without senile plaques by using a CSF Aß1-42 cut-off value of 520 pg/ml that resulted in sensitivity and specificity values of 85% and 80% respectively. Additionally, there was a significant difference in P-tau181P concentrations between AD and DLB patients (p = 0.013). A P-tau181P cut-off value of 52.8 pg/ml provided a sensitivity of 77% and specificity of 78% for the discriminating AD from DLB patients. Concomitant AD pathology in DLB patients has an influence on the CSF biomarker profile. The presence of senile plaques in DLB patients was associated with lower concentrations of Aß1-42. CSF P-tau181P levels help discriminating DLB from AD resulting in sensitivity and specificity values of almost 80%.
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Key words
dementia,csf biomarkers,ad pathology,autopsy-confirmed
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