Diminishment of High PD‐1 Expressing Peripheral Cytotoxic T Lymphocytes in Behavioral and Psychological Symptoms of Alzheimer’s Disease

Abstract

AbstractBackgroundBehavioral and psychological symptoms of dementia (BPSD) are troublesome in managing Alzheimer’s disease (AD). Growing research strongly suggests the relationship between AD and immunity of peripheral blood. Immunotherapy with blockade of PD‐L1/PD‐1 axis restored cognitive performance in the murine tauopathy model. We analyzed cytotoxic T lymphocyte (CTL) activity or possibility to be regulated, expression of PD‐1 of peripheral blood, and tried to find the correlation between PD‐1 expression and BPSD severity of AD patients.Method16 AD patients meeting NIA‐AA criteria for probable AD dementia (mean age = 80.1, 5 males,11 females) were enrolled in our study. Cognitive function was assessed by clinical dementia rating scale (CDR) and clinical dementia rating scale sum of box (CDR‐SOB). BPSD was evaluated by total neuropsychiatric inventory (NPI) scores. Higher total NPI scores suggested more serious BPSD.Histograms of CTL PD‐1 median fluorescence intensity (MFI) of 16 AD patients were compared head‐to‐head to determine a cutoff MFI value. CTL with high and low PD‐1 expressing populations were seperated. Correlation between total NPI score and CTL PD‐1 expressing population was further analyzed.ResultThe CTL subset located at the peak with the lowest MFI was defined as PD‐1dim CTL, and this subset was positively correlated to total NPI score. The other CTL subset was defined as PD‐1bright CTL, which was negatively correlated to total NPI score. No correlation was found between PD‐1 expression and CDR‐SOB (data not shown)ConclusionOur results revealed that the PD‐1 expression level of CTL decreased with enlarged total NPI scores. Interestingly, CDR‐SOB positively correlated with AD disease progression, yet BPSD could happen in even mild cognitive impairment (MCI) and very early AD stage. Although our study had limitations in sex distribution and small sample size, the results raised concern that CTL might participate in clinical manifestations of BPSD. PD‐1 expressing CTL might not correlate to global dementia progression.Further studies are expected to evaluate how peripheral CTL interplays with inflammatory molecules, excitatory and inhibitory neurons, cerebral blood perfusion, and gating of choroid plexus in the demented brain.