Human brain and serum advanced glycation end products are highly correlated: Preliminary results of their role in Alzheimer's disease and type 2 diabetes: Biomarkers (non‐neuroimaging) / novel biomarkers. (7th December 2020)

• Record Type: Journal Article
• Authors: Uribarri, Jaime; Buchman, Aron S; Cai, Weijing; Haroutunian, Vahram; Beeri, Michal Schnaider
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 4
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.045280
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Serum levels of advanced glycation end products (AGEs), a large group of pro‐oxidant and pro‐inflammatory compounds, particularly carboxymethyl lysine (CML) and methylglyoxal (MG), are generated endogenously and by dietary consumption 2 . Accumulating evidence suggests that modifying dietary AGEs consumption might affect the accumulation of AD pathology and dementia especially those with type 2 diabetes (T2D). However, there is a paucity of human data about the relationship of serum and brain levels of AGEs in older adults. Method: AGE levels were measured in serum and tissue from superior temporal gyrus of four groups of decedents: T2D+AD (N=6); T2D/no AD (N=10); no T2D+AD (N=10), and no T2D/no AD (N=10). T2D was defined by medical records (diagnosis of T2D or use of T2D medications). CERAD criteria classified pathologic diagnosis of AD. Participants with stroke were excluded. Diagnoses of hypertension and myocardial infarction were defined by ICD9. Frozen brain samples were thawed and AGE protein content was determined by competitive ELISA for MG‐H1 (3D11 mab) and CML (4G9 mab). Result: Analyses of variance demonstrated that adults with AD were older but postmortem interval and sex were similar in all four groups (see Table). The groups significantly differed in levels of serum MG, brain MG, and serum CML such that consistently the T2D+AD group had the highest levels of AGEs while the no T2D/no AD group had the lowest. There were strong correlations between serum and brain CML levels (r=0.64; p<0.0001) and MG levels (r=0.59; p<0.0001)‐See Figure; higher levels in serum were associated with higher levels in the brain. Adjusting for each of the demographic or cardiovascular variables did not alter the results. Conclusion: This study demonstrates strong and significant relationships between serum and brain AGE levels; the highest brain levels of AGEs were found in participants who had both T2D and AD. We have previously shown similar findings in mice, but we believe this is the first demonstration of such associations in humans. This was a small cross‐sectional study and the findings need to be replicated in a larger clinico‐pathological longitudinal study, which is currently ongoing, and will provide new data at AAIC2020.