Affiliations: [a] Department of Internal Medicine and Medical Specialties (DiMI), Section of Geriatrics. University of Genova, Genova, Italy | [b] Memory Clinic of Neurology Unit, Galliera Hospital, Genova, Italy | [c] Department of Experimental Medicine (DiMES), Section of Human Physiology, University of Genova, Genova, Italy | [d] IRCCS AOU San Martino-IST, Genova, Italy
Correspondence:
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Correspondence to: Fiammetta Monacelli, Department of Internal Medicine and Medical Specialties (DIMI), Viale Benedetto XV, 6 16132 Genoa, Italy. Tel./Fax: +39 0103537545; E-mail: [email protected].
Abstract: Autopsy studies have indicated brain accumulation of amyloid-β peptides as a common pathogenetic hallmark of amnestic cognitive impairment (aMCI) and overt Alzheimer's disease (AD). The pathogenesis of AD is still debated but recent reports have even designated AD as type III diabetes. This study aims to assess plasma levels of malondialdehyde, pentosidine, and insulin resistance in a group of aMCI patients, AD subjects, and age- and gender-matched controls, to confirm, beyond the accumulation of amyloid-β, the presence of a metabolic disorder, as a causative/contributive factor for AD. Patients were recruited and diagnosed as aMCI (n = 180), AD (n = 84), and age- and gender-matched controls (n = 62) at three different Italian memory clinics. Plasma insulin and glucose, plasma pentosidine and malondialdehyde (MDA), HOMA-IR and QUICKI score for insulin sensitivities indexes were collected at the basal visit. Plasma MDA levels were higher in the aMCI group who converted to AD compared to controls, stable aMCI subjects, and AD subjects (p < 0.01) respectively, while plasma pentosidine was higher compared to controls. The aMCI group showed a significant correlation between HOMA-IR, QUICKI, insulin, and MDA (p < 0.02). aMCI might be considered the early biochemical active disease stage where glycoxidation, hyperinsulinemia, and pro-amyloidogenic status are at the highest rate while overt AD might indicate the glycoxidative cascade dwindling, ending a process possibly started two decades earlier.
