title: Baseline CSF/Serum-Ratio of Apolipoprotein E and Rate of Differential Decline in Alzheimer's Disease.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Dementia Center, Department of Neurology, Georg-August-University Medical Center, Goettingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: Clinical Dementia Center, Department of Neurology, Georg-August-University Medical Center, Goettingen, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Gerlach
authors.affiliation: Clinical Dementia Center, Department of Neurology, Georg-August-University Medical Center, Goettingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmitz
authors.affiliation: Clinical Dementia Center, Department of Neurology, Georg-August-University Medical Center, Goettingen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Thom
authors.affiliation: Department of Medical Statistics, University Medical Center, Goettingen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Kramer
authors.affiliation: Department of Medical Statistics, University Medical Center, Goettingen, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Friede
authors.affiliation: Clinical Dementia Center, Department of Neurology, Georg-August-University Medical Center, Goettingen, Germany.|DZNE - German Center for Neurodegenerative Diseases, Helmholtz Society, Goettingen, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Zerr
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000150:complications*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001057:Apolipoproteins E / Q000097:blood* / Q000134:cerebrospinal fluid*; D003072:Cognition Disorders / Q000097:blood / Q000134:cerebrospinal fluid / Q000209:etiology; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009069:Movement Disorders / Q000097:blood / Q000134:cerebrospinal fluid / Q000209:etiology; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D012720:Severity of Illness Index; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer’s disease; apolipoprotein E; biomarker; cerebrospinal fluid; cognition