P2-157: Expression of CSF amyloid beta peptide patterns Alzheimer’s disease, dementia with Lewy bodies and Parkinson’s disease dementia

Biomarkers are currently warranted to support the clinical differential diagnosis of dementias. The recently established Aβ–SDS–PAGE/immunoblot enables a simultaneous quantification of amyloid–beta (Aβ) peptides Aβ1–37, 1–38, 1–39, 1–40 and 1–42 in cerebrospinal fluid (CSF). To investigate CSF of Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) for disease–specific Aβ peptide pattern. The Aβ–SDS–PAGE/immunoblot was used to analyze the CSF of 23 patients with AD, 21 with DLB, 21 PDD and 23 non–demented disease controls (NDC). A novel peptide with Aβ–like immunoreactivity (Aβ1–40*) aside the Aβ peptide quintet was constantly observed in all 88 CSF samples investigated. We have characterized this peptide to represent an oxidized derivate of Aβ1–40 using electrophoresis, immunodetection and MALDI–TOF analysis. Moreover, our data indicate an alpha–helical secondary structure of the peptide. AD and DLB shared a significant decrease of CSF Aβ1–42 and a percentage elevation of Aβ1–40*. The drop of CSF Aβ1–42 was most pronounced for AD, whereas carboxterminally shorter Aβ peptides (e.g. Aβ1–37 and Aβ1–38) tended to increase only in AD. The introduction of a ratio of Aβ1–42 to Aβ1–37 and Aβ1–38, respectively, discriminated all diagnostic groups from each other, except DLB from PDD. The percentage increase of Aβ1–40* was most prominent in DLB. The sensitivity for detection of DLB was 81% with a specificity of 71% and 70% among PDD and a combined group (AD, PDD and NDC), respectively. Interestingly, DLB and PDD exhibit distinct clinical temporal course of disease accompanied by distinct neurochemical phenotypes in CSF, despite their similar neuropathological appearance. Despite some overlap, especially with regard to AD and DLB, the distinct neurochemical phenotypes in CSF indicate disease–specific interactions of each ongoing neurodegenerative dementia process with APP metabolism in AD, DLB and PDD. The evaluation of CSF Aβ peptide patterns come closest to the requirements for a biomarker candidate and may be promising for future use in multiparametric approaches towards the differential diagnosis of dementias.