CSF ApoE predicts clinical progression in nondemented APOEε4 carriers

Possible associations between cerebrospinal fluid (CSF) and plasma apolipoprotein E (ApoE) concentration and early clinical and pathophysiological manifestation of Alzheimer's disease were studied in a large and well-defined population of nondemented patients. CSF and plasma ApoE concentrations were related to CSF A beta 42, Tau and pTau levels and clinical characteristics in patients with subjective cognitive decline (n = 207) or mild cognitive impairment (n = 213) aged 64.2 +/- 9.0 years, with a 2.5 +/- 1.5 years follow-up. A 1 standard deviation increase in log-transformed CSF ApoE concentrations increased the risk of clinical progression in APOE epsilon 4 carriers 1.5 times (hazard ratio [95% confidence interval] 1.5 [1.1e2.0]), while this was not the case in APOE epsilon 4 noncarriers (hazard ratio [95% confidence interval] 1.0 [0.8e1.2]). Plasma ApoE did not predict clinical progression. Using linear regression models, strong associations between CSF ApoE levels and CSF Tau (beta 0.51 [0.38-0.65]) and pTau (beta 0.53 [0.40-0.60]) values were observed in APOE epsilon 4 carriers. We hypothesize CSF Apo epsilon 4 increases risk of clinical progression through its association with CSF Tau in APOE epsilon 4 carriers. Development of Alzheimer's disease in APOE epsilon 4 noncarriers may be unrelated to ApoE concentration. (C) 2017 Elsevier Inc. All rights reserved.