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

Objectives: We examined the relationship between CSF amyloid beta peptide ( A beta) concentration and AD severity in 31 probable AD patients and explor ed whether APOE genotype modifies this relationship. Background: A beta dep osition in AD brains has been correlated with disease severity and with APO E-epsilon 4 allele frequency. Few studies have examined the effects of APOE genotype on the relationship between CSF AP and disease severity in an ant emortem sample. Methods: Patients carried the clinical diagnosis of probabl e 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 w ithin 3 months of CSF collection. CSF was analyzed for A beta 1-40 and A be ta 1-42 by sandwich ELISAs, and APOE genotype was determined by PCR run fro m blood. Correlations were performed between MMSE score and A beta 1-40 and A beta 1-42 concentrations while controlling for potential confounding var iables. Results: CSF measures of A beta 1-40 and A beta 1-42 concentrations were correlated with each other (r = 0.56, df = 28, p < 0.01). CSF A beta 1-40 and A beta 1-42 concentrations were positively correlated with MMSE sc ore. The negative association between CSF A beta measures and disease sever ity remained significant after controlling for age (A beta 1-40 and MMSE sc ore: r = 0.46, df = 28, p = 0.01; A beta 1-42 and MMSE score: r = 0.35, df = 28, p = 0.05). Among the APOE-epsilon 3/3 homozygotes there was a signifi cant positive correlation only between A beta 1-42 and MMSE score (A beta 1 -42, r = 0.94, p = 0.02; A beta 1-40, r = 0.79, p = 0.11). Conclusions: We hypothesize that an increased deposition of Ap in plaques results in decrea sed CSF A beta concentration. The stronger relationship between MMSE score and CSF A beta, specifically in APOE-epsilon 3/3 homozygotes, suggests that patients with APOE-epsilon 3/3 genotype may have different pathogenic mech anisms than the other genotypes for A beta deposition or clearance.