The Study Of The Correlation Between The Novel Adipokine C1qTNF-related Protein 4(CTRP4)and Alzheimer’s Disease

Alzheimer’s disease(AD)is a progressive neurodegenerative disorder of the brain,which is characterized by the formation of extracellular amyloid plaques(or senile plaques)and intracellular neurofibrillary tangles.It is the most common form of dementia,accounting for 50%to 60%of cases at the autopsy and in clinical series.Current drugs improve symptoms,but do not have profound disease-modifying effects,which makes effective treatment of AD become the biggest unmet medical need in neurology.AD is characterized by memory loss as well as impaired locomotor ability,reasoning,and judgement.In AD,the accumulation of β-amyloid(Aβ)in the brain perturbs physiological functions of the brain.The first responders to Aβ accumulation are the microglia,which are recruited to amyloid plaques.However,microglia becomes dysfunctional in AD and shows a significant reduction in their ability to phagocyte and degradate Aβ,but maintain their ability to produce pro-inflammatory cytokines,which are increasingly implicated in the pathogenesis of AD.The preclinical phase of Alzheimer’s disease occurs years,possibly decades,before the onset of clinical symptoms.Identification of subjects at the early stages of Alzheimer’s disease is fundamental for drug development and possible intervention of cognitive decline.The two important phases during the cognitive decline are SCD and aMCI.Amnestic mild cognitive impairment(aMCI)is the transition stage between the normal aging process and dementia itself.Subjective cognitive decline(SCD)was defined as self-reported cognitive decline before deficits could be detected by cognitive tests.Subjects with SCD have an increased risk of underlying AD pathology and represent a stage preceding amnesic mild cognitive impairments,which is a well-established precursor of AD.CTRP4 is a unique member of C1q family,prcessing two tandem globular Clq domians.CTRP4 is expressed highly in the brain.Similarly,lower concentration of CTRP4 has been detected in the serum of subjects with SCD than normal subjects.Therefore,we investigated the probable role of CTRP4 in the progression of AD,using C1qtnf4-eK01 mouse model.Here we report for the first time that the lower CTRP4 may promote memory deficits in C1qtnf4-eKO1mice.Furthermore,CTRP4 exhibits the potential to promote the phagcytic activity of microglia.Collectively,our results indicate that CTRP4 may act as a potential player in AD.