CSF Aβ1-42 AS THE PATHOLOGICAL AD BIOMARKER IN TYPE 2 DIABETES MELLITUS PATIENTS

Abstract

Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer's disease (AD), and amyloid β1–42 (Aβ1–42) is a classic pathological AD biomarker. However, it is largely unknown how the Aβ1–42 in cerebrospinal fluid (CSF) functions as a pathological biomarker in T2DM patients. Data from the Alzheimer's Disease Neuroimaging Initiative was used. Participants with T2DM were separated from those without T2DM by keywords from their medical history database. A two-way analysis of covariance (ANCOVA) model was used to analyze how T2DM and baseline diagnosis affects the CSF Aβ1–42. Relation between the CSF Aβ1–42 and cortical amyloid burden assessed by florbetapir F 18 PET were also reported. Then cortical amyloid burden and its distribution among cortical sub-regions were compared between the T2DM and non-diabetic groups. The CSF Aβ1–42 for the T2DM group is 204.35 ± 9.40 pg/ml (95% CI: 185.89–222.80 pg/ml, n = 76), which is higher than the same measure in the non-diabetic group of 168.58 ± 4.49 pg/ml (95% CI: 159.76–177.40 pg/ml, n = 731, p = 0.001). The CSF Aβ1–42 is negatively correlated with the cortical florbetapir 18F standardized uptake value ratio (SUVR) for the β amyloid (r = -0.701, n = 812, p<0.005). The mean cortical florbetapir 18F SUVR for the T2DM group is 1.11 ± 0.05 (95% CI: 1.02–1.20, n = 77), which is lower than the same measure in the non-diabetic group of 1.23 ± 0.02 (95% CI: 1.18–1.27, n = 735, p = 0.02). The lower corticla amyloid is seen in all the examined cortical subregions. A higher CSF Aβ1–42 and a lower cortical amyloid burden in participants with T2DM than those without T2DM suggest that T2DM-related cognitive impairment might have a different mechanism than AD.