Active Learning Strategies in Veterinary Medicine: A Literature Review.

A growing body of evidence demonstrates that diabetes confers deleterious impacts on the central and peripheral nervous systems and is linked to neuroinflammatory and neurodegenerative disorders, including cognitive impairment syndromes and dementias (–). Indeed, recent literature suggests that the chronic inflammation and immune dysregulation, impaired glucose metabolism, and insulin signaling dysfunction seen in type 2 diabetes (T2D) may play a direct role in the multifactorial pathogenesis of neurodegenerative disorders (, , ). Further, some of the leading complications of diabetes, such as diabetic retinopathy (DR), are characterized by a combination of microvascular dysfunction and neurodegenerative pathophysiology and may reflect the presence of central and/or systemic neurodegeneration (–). However, existing studies are largely centered around adults with T2D, and there has been limited study with inconsistent findings on the association between T1D and systemic and/or central neurodegenerative pathology (, –). The pathophysiology underlying neurodegeneration and neuroinflammation can begin decades prior to the onset of clinical symptoms (, ). Advances in the field of aging provide new, less-invasive avenues for exploration of these processes, even in the earliest stages of the disease trajectory. One such method is quantification of plasma levels of biomarkers of neurodegeneration and neuroinflammation, including phosphorylated Tau-181 (pTau-181), total tau protein (Tau), and amyloid beta 42/amyloid beta 40 (Aβ42/40), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) protein (, ). Studies in older adults have shown that lower or decreasing plasma levels of Aβ42/40 and higher or increasing plasma levels of pTau-181 are associated with brain amyloid deposition, which is a hallmark feature of Alzheimer’s Disease (AD) neuropathology (, –). More recently, higher plasma levels of pTau-181 have been linked to other systemic neurodegenerative diseases (, ). Higher or increasing levels of Tau are associated with brain tau and amyloid pathology, as well as serving as a non-specific marker of neural damage (, , , ). Higher or increasing levels of GFAP are a marker of glial activation and downstream neuroinflammation (, , ), and higher or increasing plasma levels of NfL are suggestive of non-specific neural damage (, , ). Given the paucity of data regarding the relationship between T1D and neurodegenerative pathology, the current study sought to examine the association between T1D and related characteristics and biomarkers of neurodegeneration and neuroinflammation. Here, we hypothesized that T1D would be associated with higher plasma levels of pTau-181, Tau, GFAP, and NfL, and lower plasma levels of Aβ42/40.