Correlation between CSF amyloid beta 1-42 and plasma glucose/insulin is modulated by ApoE4 polymorphism in early onset sporadic Alzheimer's disease (EOAD).

Type2 diabetes (T2D), insulin resistance and presence of apoE4 allele are associated to higher risk of developing Alzheimer's disease (AD), however little evidence of a possible direct connection between glucose metabolism and amyloid beta 1-42 (Aß)accumulation was found in human. Aim of the present study was to evaluate the possible association between AD CSF biomarkers levels and glucose/insulin metabolism in sporadic EOAD. 20 sporadic EOAD (NINCDS-ADRDA) consecutive patients, mean age 64.1 ± 4.9y, 65% females, MMSE 17.5 ± 5.9 were studied. T2D subjects were excluded. CSF levels of A ß 1-42 , total TAU and P-TAU 181 were quantified by ELISA (Innogenetics); apoE genotype was determined by restriction polymorphism analysis. an inverse correlation was found between concentrations of CSF A ß 1-42 and plasmaglucose and insulin levels, and insulin resistance (HOMA-IR), respectively: r = −0.646; p = 0.002; r = −0.462; p = 0.04; r = −0.563; p = 0.01, the correlation with fasting glycaemia was confirmed in two distinct samples. When the patient population was divided by apoE4polymorphism we found that the correlation was present only in theapoE4+ group (r = −0.736, p = 0.01). In addition, CSF total TAU levels were significantly higher in ApoE4 carriers (p = 0.03). Glycaemia and insulin resistance appear to play a direct role in A 1-42 CSF metabolism, at least in this select population of sporadic EOAD patients. When ApoE4 is associated with insulin resistance the patients may be particularly exposed to neurodegeneration as indicated by the higher CSF TAU levels.