Affiliations: [a] Clinical Dementia Center, Department of Neurology, Georg-August-University Medical Center, Goettingen, Germany | [b] Department of Medical Statistics, University Medical Center, Goettingen, Germany | [c] DZNE – German Center for Neurodegenerative Diseases, Helmholtz Society, Goettingen, Germany
Correspondence:
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Correspondence to: Dr. Christian Schmidt, Department of Neurology, Clinical Dementia Center, Georg August UniversityHospital, Robert-Koch-Str. 40, 37075 Goettingen, Germany. Tel.:+49 551 39 6636; Fax: +49 551 39 7020; [email protected]
Abstract: Background/Objective: Apolipoprotein E (ApoE) has an active part 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 biomarker potentially predictive of cognitive, functional, or motor decline, we analyzed the CSF to serum ratios of ApoE levels (CSF/serum ApoE) in AD patients in this regard. Methods: Subjects with newly diagnosed AD were followed within a longitudinal observational study (rpAD study). Annual neuropsychological testing and physical examination were performed. Multiple regression analyses were used to determine possible associations of the ApoE CSF/serum concentration ratios and velocity of decline on a variety of cognitive, functional and motor scales (MMSE, iADL, bADL, GDS, UPDRSIII) adjusted for relevant co-variables. Results: CSF/serum ratios of ApoE levels were associated with progression on the UPDRSIII (change of UPDRSIII slope [pt/yr] per unit of ApoE CSF/serum = –0.06, p < 0.01) and instrumental ADL scale (change of iADL slope [pt/yr] per unit of ApoE CSF/serum = 0.01, p = 0.01) (“the lower the ratio, the faster the deterioration” and vice versa). Secondarily, higher age at onset was associated with faster UPDRSIII progression, antidepressant use with faster iADL decline, and better baseline function with more rapid decline on either MMSE, iADL, or GDS scale. Conclusion: Here, CSF/serum ApoE at time of AD diagnosis was shown to be inversely associated with medium-term functional and motor progression. Whether this ratio qualifies for the use as a predictive biomarker must be validated in larger cohort studies over the long term.
Keywords: Alzheimer’s disease, apolipoprotein E, biomarker, cerebrospinal fluid, cognition
