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Hippocampal atrophy appears to be an independent effect, potentially serving as a common neuropathological basis for the association of T2DM with both dementia and depression [100]

Furthermore, since the instability of Ala 2 is caused by degradation of DPP-4, Ala 2 may not need to be changed if the peptide is fused with albumin or Fc domain (discussed later) for long-term activity, which creates a steric hindrance to prevent the enzyme from getting close

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3.3 Mitochondrial dysfunction and oxidative stress Chronic hyperglycemia in patients with T2DM leads to peripheral insulin resistance, whereas impaired insulin signaling pathways in the brains of patients with AD lead to brain insulin resistance, both of which are closely related to mitochondrial dysfunction and OS (Zhang et al., 2023)

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