Joint Effect of Hypertension and APOE Genotype on CSF Biomarkers for Alzheimer's Disease

We examined the impact of hypertension on cerebrospinal fluid (CSF) biomarkers amyloid-beta(1-42) (A beta(42)), total tau (tau), and phosphorylated tau at threonine 181 (ptau-181), and assessed the modifying role of APOE genotype in this relation in 546 patients (mean age 65 +/- 10, 47% female) from our memory-clinic. Of these patients 150 had subjective complaints, 140 were diagnosed with mild cognitive impairment, and 256 with Alzheimer's disease. Linear regression analyses adjusted for age, gender, and diagnosis showed that the association of hypertension with tau and ptau-181 was modified by APOE genotype (p-values for interaction < 0.05). In APOE epsilon 4 homozygotes (n = 74), and to a lesser extent in APOE epsilon 4 heterozygotes, hypertension was associated with higher tau and ptau-181 levels; beta (95% CI) were 188 (11; 364) pg/mL and 22 (3; 42) pg/mL for the APOE epsilon 4 homozygotes. Hypertension was not associated with A beta(42) levels, and APOE genotype did not modify this relation. Our findings suggest that hypertension is directly related to tau pathology in APOE epsilon 4 homozygous carriers.