TLR4 is a link between diabetes and Alzheimer’s disease

•TLR4 is involved in the physiological and pathological progress of DM and AD respectively.•In DM, chronic TLR4 activation may contribute to the insulin resistance.•In AD, chronic long-term TLR4 activation may lead to Aβ deposition.•TLR4 as a potential link between DM and AD is reviewed.•TLR4 as a link of between DM and AD further explain the theory that AD is regarded as types 3 diabetes.

Recently, more and more studies have shown that there is an essential link between diabetes mellitus (DM) and Alzheimer’s disease (AD). In addition, innate immunity plays an important role in the occurrence and development of DM and AD, which increase the risk of developing type 2 diabetes (T2D) and AD. Although the pathogenesis of those diseases is still a matter of debate, the important role of Toll-like receptor 4 (TLR4) in the two diseases has been receiving much attention at present. TLR4 and insulin resistance do have close ties, and chronic TLR4 activation may contribute to the insulin resistance. Aside from this, TLR4-mediated chronic inflammation also causes many DM complications such as diabetic nephropathy, diabetic retinopathy and diabetic neuropathy and has a profound impact on the internal environment of the body and brain’s microenvironment. In parallel, TLR4 is widely distributed in the brain and also has an important role in the central nervous system (CNS) via regulation of neuroinflammation. The cerebrum under the circumstances of insulin resistance may lead to mitochondrial dysfunction in neurons. Interestingly, in the initial stage, the activation of TLR4 has a useful scavenging effect on amyloid beta (Aβ), but chronic long-term activation leads to Aβ deposition in the brain. Therefore we speculate that the TLR4 signaling pathway may be a potential link between DM and AD.