Age-Dependent Decline in the Apolipoprotein E Level in Cerebrospinal Fluid from Control Subjects and Its Increase in Cerebrospinal Fluid from Patients with Alzheimer’s Disease
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Medientyp:
E-Artikel
Titel:
Age-Dependent Decline in the Apolipoprotein E Level in Cerebrospinal Fluid from Control Subjects and Its Increase in Cerebrospinal Fluid from Patients with Alzheimer’s Disease
Beschreibung:
<jats:p>In order to address the significance of apolipoprotein E (apoE) in the pathogenesis as well as the clinical diagnosis of Alzheimer’s disease (AD), we measured its level in cerebrospinal fluid (CSF) from randomly selected Japanese control subjects at various ages (n = 36), which included 14 age-matched controls, and from AD patients including early-onset (n = 11, EOAD) and late-onset (n = 14, LOAD) cases. The CSF apoE level in controls linearly decreased during aging to over 80 years (r<sup>2</sup> = 0.323, p < 0.0001). The CSF apoE level in AD patients was 31.9% elevated compared to the age-matched controls (n = 14, p < 0.05) and linearly increased with a decrement of the patients’ Mini Mental State Examination scores. Moreover, the CSF apoE level of EOAD patients (n = 11) was higher than that of LOAD patients (n = 14, p < 0.05), whose <i>APOE</i> ε4 allele frequency was significantly higher than that of controls (χ<sup>2</sup> = 7.16, p < 0.03). Two-dimensional gel electrophoretic analysis of the heparin-Mn<sup>2+</sup>-precipitable lipoprotein fraction in CSFs showed that the ratio between the level of CSF apoA-I and that of CSF apoE of controls was significantly higher than those of all AD and LOAD subjects (p < 0.01, p < 0.05), while the CSF apoA-I-to-apoE ratios of the two AD groups were not significantly different. These results suggest that overproduction of apoE protein may be a consequence of astroglial response to neurodegeneration in AD and that the determination of CSF apoliprotein levels serves as a clinical marker for monitoring the progression of AD.</jats:p>