Besides that, Aβ can enter multiple cell types (eg. For instance, the interaction between amyloid precursor protein (APP) and cell-surface LRP1 leads to increased endosomal trafficking of APP, accelerating Aβ production. As a cell surface receptor, LRP1 can control the endocytosis of multiple ligands, mediate cell signaling transductions and regulate gene expression through its intracellular domain 9, 10, 11.
In plasma, soluble LRP1 binds to peripheral Aβ, and consequently prevents free Aβ access to the brain 8. There are two forms of LRP1–soluble LRP1 and cell-surface LRP1. In the central nervous system, LRP1 plays an important role in controlling Aβ metabolism and maintaining brain homeostasis. LRP1 is ubiquitously expressed in various tissues, especially high in liver, lung and brain 7. Low density lipoprotein receptor-related protein 1 (LRP1) has been widely studied due to its pleiotropic roles in AD pathogenesis 6. Variants associated with AD have been detected in more than 20 genes, which are involved in metabolism, inflammation, synaptic activity and intracellular trafficking 4, 5. It is believed that genetic factors, lifestyle and environmental factors synergistically give rise to AD. Besides, loss of neurons and white matter, congophilic angiopathy, inflammation, and oxidative damage are also important pathological features of AD. It is essentially characterised by cerebral senile plaques laden with β-amyloid peptide (Aβ), dystrophic neurites in neocortical terminal fields as well as neurofibrillary tangles of hyperphosphorylated microtubule-associated protein tau 3. Considering some limitations of our meta-analysis, further large-scale studies should be done to reach a more comprehensive understanding.Īlzheimer’s disease (AD), a progressive and lethal neurodegenerative disorder, has become a global challenge for the 21st century 1, 2. In conclusion, our meta-analysis suggested that LRP1 C766T polymorphism was associated with lower risk of AD in Asian, and could reduce LOAD risk especially. The combined analysis showed that there was no significant association between LRP1 C766T polymorphism and AD susceptibility (TT + CT versus CC: OR = 0.920, 95% CI = 0.817–1.037, P = 0.172). Therefore, we conducted a meta-analysis containing 6455 AD cases and 6304 controls from 26 independent case–control studies to determine whether there was an association between the LRP1 C766T polymorphism and AD susceptibility. However, results in different studies have been contradictory. Low density lipoprotein receptor-related protein 1 (LRP1) C766T polymorphism (rs1799986) has been extensively investigated for Alzheimer’s disease (AD) susceptibility.