Molecular and biochemical trajectories from diabetes to Alzheimer’s disease: A critical appraisal

Table 1 Relevant reports bridging Alzheimer’s disease and diabetes mellitus

Ref.	Key findings
Adolfsson et al[47]	Hypoglycemic condition can ameliorate brain status in AD
Razay et al[48]	Disturbances in glucose metabolism and hyper-insulinemia in female AD patients are responsible for cognitive decline
Ruigómez et al[58]	Documented a relationship between non-insulin dependent diabetes and neuropathy
Li et al[50]	Defective insulin signaling is a shared degenerative cascade in disease pathology of both AD and DM
Ke et al[59]	Amylin deposition in pancreatic islets of T2D patients whereas, Aβ and NFTs deposition in AD brain are common hallmarks feature of diabetes and Alzheimer’s in terms of protein deposition
Saini[53]	Elucidated cellular and molecular mechanisms of insulin resistance and provided understanding for the molecular therapeutic targets
Park[54]	T2D and AD have some common pathogenic alterations like defects in insulin signaling, Aβ clearance, glucose metabolism, O-GlcNAcylation, Aβ aggregation by AGEs, inflammation, oxidative stress and circulating cortisol levels
Correia et al[55]	Amyloidogenesis and mitochondrial dysfunction are common denominators potentiating brain dysfunctions
Talbot et al[57]	Brain insulin signaling pathway including IGF-1R → IRs-2 → PI3K signaling is directly involved in AD and thus one of a causal factor in disease pathogenesis

AD: Alzheimer’s disease; DM: Diabetes mellitus; T2D: Type 2 diabetes; NFTs: Neurofibrillary tangles; Aβ: Amyloid beta; AGEs: Advanced glycation end products; IGF-1: Insulin like growth factor-1; IRs: Insulin receptors; PI3K: Phosphatidylinositide 3-kinases.

Table 2 Symptoms of Alzheimer’s disease symptoms in diabetes mellitus patients and symptoms of diabetes mellitus in Alzheimer’s disease patients

Ref.	Key findings
Gasparini et al[75]	In T2D patients insulin metabolism dysfunction accelerates AβPP/Aβ trafficking from trans-Golgi network, a major site for a Aβ generation
Phiel et al[76]	Some studies claim for the presence of downstream regulators of insulin signaling pathway which are involved in cleavage of AβPP at gamma-secretase site, a determining site for Aβ amyloidogenicity
Steen et al[24]	Extensive dysfunction of IGF-I and IGF II signaling mechanisms reported in AD brain
Rivera et al[66]	Insulin and IGF gene expression altered with abnormal receptor binding in AD brain

AD: Alzheimer’s disease; T2D: Type 2 diabetes; Aβ: Amyloid beta; IGF: Insulin like growth factor.