Comparative analysis of cerebrospinal fluid biomarkers in the differential diagnosis of neurodegenerative dementia.

INTRODUCTION: The analysis of cerebrospinal fluid biomarkers gains importance in clinical routine and is effective in substantiating dementia diagnosis in the differential diagnostic context. METHODS: We evaluated the levels of ß-amyloid (Aß) 42, Aß40, tau, and P-tau in a large patient population subdivided into prion diseases, tauopathies, synucleinopathies, and controls. Diagnostic test evaluation was assessed by ROC area under the curve analysis. RESULTS: High tau levels were detected in sporadic Creutzfeldt-Jakob disease (sCJD) and high P-tau levels in Alzheimer's disease (AD) and sCJD. Aß40 was lower exclusively in prionopathies, but low Aß42 was detected in AD, sCJD, and Lewy body dementia. When disease groups were stratified according to the underlying proteinopathy, we detected disease-type specificities for all biomarkers. P-tau/tau, Aß42/40, Aß42/tau, and Aß40/tau ratios proved valuable in discriminating disease groups and controls, especially P-tau/tau ratio in the identification of sCJD cases. DISCUSSION: Combining the biomarker panel allows differentiating between various types of neurodegenerative dementias and contributes to a better understanding of their pathophysiological processes.

Cerebrospinal fluid apolipoprotein E concentration and progression of Alzheimer's disease.

BACKGROUND/OBJECTIVE: Apolipoprotein E plays a role in the pathogenesis of Alzheimer's disease (AD). Cerebrospinal fluid (CSF) and plasma level alterations have been reported in AD patients. In search of a potential biomarker, which would be predictive of cognitive, functional, or motor decline, we analyzed CSF apolipoprotein E (ApoE) levels of AD patients in this regard. METHODS: Subjects with newly diagnosed AD enrolled into an observational study were followed up longitudinally. Neuropsychological testing and physical examination were performed annually. In a sub-cohort of patients, where baseline CSF ApoE concentration values were available, multiple regression analyses were used to determine possible associations of CSF ApoE concentration and speed of decline on different cognitive, functional, and motor scales (MMSE, iADL, bADL, GDS, UPDRSIII) adjusting for possible confounders. RESULTS: No association of CSF ApoE levels and speed of decline on the various scales could be established (p = 0.09 to 0.88). Nevertheless, the use of neuroleptic drugs could be linked to higher velocity of global and extrapyramidal deterioration (p = 0.04 and 0.05 for GDS and UPDRSIII, respectively), but not to other outcomes (MMSE, bADL, and iADL). CONCLUSION: Herein, CSF ApoE at time of AD diagnosis could not be shown to be a viable biomarker for future cognitive, functional, or motor decline. Expectedly, the use of neuroleptic drugs was associated with detrimental effects.