CSF beta-amyloid, cognition, and APOE genotype in alzheimer's disease

Objectives: We examined the relationship between CSF amyloid beta peptide (Aβ) concentration and AD severity in 31 probable AD patients and explored whether APOE genotype modifies this relationship. Background: Aβ deposition in AD brains has been correlated with disease severity and with APOE-ε4 allele frequency. Few studies have examined the effects of APOE genotype on the relationship between CSF Aβ and disease severity in an antemortem sample. Methods: Patients carried the clinical diagnosis of probable AD and did not have serious medical illness, current or past diagnosis of mood disorder, schizophrenia or alcoholism, or current psychotic features. The Mini-Mental State Examination (MMSE) was administered to the patient within 3 months of CSF collection. CSF was analyzed for Aβ1-40 and Aβ1-42 by sandwich ELISAs, and APOE genotype was determined by PCR run from blood. Correlations were performed between MMSE score and Aβ1-40 and Aβ1- 42 concentrations while controlling for potential confounding variables. Results: CSF measures of Aβl-40 and Aβ1-42 concentrations were correlated with each other (r = 0.56, df = 28, p < 0.01), CSF Aβ1-40 and Aβ1-42 concentrations were positively correlated with MMSE score. The negative association between CSF Aβ measures and disease severity remained significant after Controlling for age (Aβ1-40 and MMSE score: r = 0.46, df = 28, p = 0.01; Aβ1-42 and MMSE score: r = 0.35, df = 28, p = 0.05). Among the APOE-ε3/3 homozygotes there was a significant positive correlation only between Aβ1-42 and MMSE score (Aβ1-42, r = 0.94, p = 0.02; Aβ1-40, r = 0.79, p = 0.11). Conclusions: We hypothesize that an increased deposition of Aβ in plaques results in decreased CSF Aβ concentration. The stronger relationship between MMSE score and CSF Aβ, specifically in APOE-ε3/3 homozygotes, suggests that patients with APOE-ε3/3 genotype may have different pathogenic mechanisms than the other genotypes for Aβ deposition or clearance.