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 Aβ42, 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 APOEε4 carriers 1.5 times (hazard ratio [95% confidence interval] 1.5 [1.1–2.0]), while this was not the case in APOEε4 noncarriers (hazard ratio [95% confidence interval] 1.0 [0.8–1.2]). Plasma ApoE did not predict clinical progression. Using linear regression models, strong associations between CSF ApoE levels and CSF Tau (β 0.51 [0.38–0.65]) and pTau (β 0.53 [0.40–0.60]) values were observed in APOEε4 carriers. We hypothesize CSF ApoE4 increases risk of clinical progression through its association with CSF Tau in APOEε4 carriers. Development of Alzheimer's disease in APOEε4 noncarriers may be unrelated to ApoE concentration.