Cerebrospinal fluid biomarkers for neuropsychological symptoms in early stage of late-onset Alzheimer's disease

Purpose: In addition to testing blood, cerebrospinal fluid (CSF) has been analyzed in the search for biomarkers. The aim of this study was to identify biomarkers in CSF for neuropsychological symptoms in early-stage late-onset Alzheimer's disease (LOAD). Methods: CSF levels of beta-amyloid 1-42 (Aβ42), F₂-isoprostanes (F₂-IsoPs) and F₄-neuroprostanes (F₄-NPs) were assayed in nine patients with mild Alzheimer's disease (AD), nine patients with amnestic mild cognitive impairment (a-MCI) and nine individuals with normal mental function. The three groups underwent neuropsychological testing. Results: CSF levels of F₂-IsoPs and F₄-NPs did not significantly differ among the three groups. Aβ42 in CSF was significantly higher in the control group compared with the mild AD group (p < 0.001) and a-MCI group (p = 0.03). There was a significant positive correlation between the level of F₂-IsoPs and Aβ42 in the a-MCI group and between the level of F₂-IsoPs and F₄-NPs in the mild AD group. In comparisons between the mild AD group and a-MCI group combined, the cognitive impairment (CI) group, with the control group, the median levels of F2-IsoPs and F₄-NPs were significantly higher in the CI group and median level of Aβ42 was significantly lower in the CI group. Both the levels of F₂-IsoPs and Aβ42 were significantly negatively correlated with paranoid and delusional ideation and total score for the Behavioral Pathology in Alzheimer's Disease Scale (BEHAVE-AD). Conclusions: The findings suggest CSF levels of Aβ42 and F₂-IsoPs are associated with the severity of neuropsychological symptoms.