There was mounting evidence that mitochondrial dysfunction is linked to diabetes’s role in Alzheimer’s disease (AD) development. Neuronal mitochondrial proteins are discovered at quantities similar to those observed in brain neurons in plasma neuronal-derived exosomes (NDEs). For a study, researchers investigated the ability of mitochondrial proteins in plasma NDEs to predict cognitive impairment and brain damage in diabetic patients. 

The research participants with type 2 diabetes mellitus (T2DM) included 41 cognitively normal control subjects, 97 people with moderate cognitive impairment (MCI) (68 people with stable MCI; 29 people with progressing MCI), and 36 people with Alzheimer’s disease (AD dementia). ELISA kits were used to assess plasma neuroexosomal proteins. The Spearman correlation test was performed to examine the relationships between plasma neuroexosomal mitochondrial proteins and other primary indicators of Alzheimer’s disease. Using receiver operating characteristic curve analysis, mitochondrial proteins were shown to have high diagnostic accuracy for progressing MCI and AD. Cox proportional hazard regression was used to examine the relationships between mitochondrial proteins and the progression from MCI to AD. 

Patients with T2DM with AD dementia and progressing MCI had substantially lower plasma levels of neuroexosomal NADH ubiquinone oxidoreductase core subunit S3 (NDUFS3) and succinate dehydrogenase complex subunit B (SDHB) than cognitively normal people (P<0.001 for both groups). They also discovered that plasma neuroexosomal NDUFS3 and SDHB levels were lower in patients with progressing MCI than in those with stable MCI. Both plasma neuroexosomal NDUFS3 and SDHB can be used to diagnose Alzheimer’s disease. Low plasma neuroexosomal SDHB levels substantially indicated MCI to AD conversion. 

Furthermore, decreased mitochondrial protein levels were linked to the rate of hippocampus and gray matter shrinkage, as well as lower AD hallmark cortical thickness in patients with increasing MCI during the course of the study. The findings suggested that plasma neuroexosomal NDUFS3 and SDHB levels were already elevated in participants with diabetes at the early clinical stage of AD, indicating the potential of plasma neuroexosomal mitochondrial proteins as diagnostic and prognostic biomarkers for the earliest symptomatic stage of AD.