%0 Journal Article %J J Alzheimers Dis %D 2023 %T Age-Related Association Between APOE ɛ4 and Cognitive Progression in de novo Parkinson's Disease. %A Liu, Jia-Yao %A Ma, Ling-Zhi %A Wang, Jun %A Cui, Xin-Jing %A Sheng, Ze-Hu %A Fu, Yan %A Li, Meng %A Ou, Ya-Nan %A Yu, Jin-Tai %A Tan, Lan %A Lian, Yan %K Aged %K Apolipoprotein E4 %K Cognition %K Cognitive Dysfunction %K Disease Progression %K Genotype %K Heterozygote %K Humans %K Parkinson Disease %X

BACKGROUND: APOE ɛ4 genotype was correlated with exacerbation of pathology and higher risk of dementia in Parkinson's disease (PD). Meanwhile, the differential influence of APOE ɛ4 on cognition in young and old individuals interpreted as antagonistic pleiotropy.

OBJECTIVE: To examine whether the effect of APOE ɛ4 on cognitive progression in de novo PD is age dependent.

METHODS: In this study, 613 de novo PD patients were recruited from Parkinson's Progression Markers Initiative (PPMI). To examine the age-dependent relationship between APOE ɛ4 and cognitive changes, we added 3-way interaction of APOE ɛ4*baseline age*time to the linear mixed-effect (LME) models and evaluated the specific roles of APOE ɛ4 in the middle age group and elderly group separately. Cox regression was utilized to examine the progression of cognition in age-stratified PD participants.

RESULTS: Age significantly modified relationship between APOE ɛ4 and cognitive changes in most cognitive domains (pinteraction <0.05). In the elderly group, APOE ɛ4 carriers showed steeper decline in global cognition (p = 0.001) as well as in most cognitive domains, and they had a greater risk of cognitive progression (adjusted HR 1.625, 95% CI 1.143-2.310, p = 0.007), compared with non-carriers. However, in the middle age group, no significant relationships between APOE ɛ4 and cognitive decline can be detected.

CONCLUSION: Our results indicated that the APOE ɛ4 allele has an age-dependent effect on cognitive decline in PD patients. The underlying mechanisms need to be investigated in the future.

%B J Alzheimers Dis %V 91 %P 1121-1132 %8 2023 %G eng %N 3 %R 10.3233/JAD-220976 %0 Journal Article %J J Alzheimers Dis %D 2022 %T The Correlation of Tau Levels with Blood Monocyte Count in Patients with Alzheimer's Disease. %A Sun, Hao-Lun %A Zhou, Fa-Ying %A Chen, Dong-Wan %A Tan, Cheng-Rong %A Zeng, Gui-Hua %A Liu, Yu-Hui %A Wang, Jun %A Bu, Xian-Le %A Wang, Yan-Jiang %A Li, Hui-Yun %A Jin, Wang-Sheng %K Aged %K Aged, 80 and over %K Alzheimer Disease %K Amyloid beta-Peptides %K Brain %K Cognitive Dysfunction %K Cohort Studies %K Female %K Humans %K Male %K Monocytes %K tau Proteins %X

BACKGROUND: Recent studies have shown that monocytes can phagocytize the tau protein, which may ameliorate tau-type pathology in Alzheimer's disease (AD). However, there are few clinical studies on the relationship between monocytes and tau-type pathology in AD patients.

OBJECTIVE: We aimed to explore changes in peripheral monocytes and their association with tau protein in AD patients.

METHODS: A total of 127 clinically diagnosed AD patients and 100 age- and sex-matched cognitively normal controls were recruited for analysis of the correlation of plasma tau levels with the blood monocyte count. Cerebrospinal fluid (CSF) samples from 46 AD patients and 88 controls were further collected to analyze the correlation of CSF tau and amyloid-β (Aβ) levels with the blood monocyte count. 105 clinically diagnosed mild cognitive impairment (MCI) patients and 149 age- and sex-matched cognitively normal controls were recruited from another cohort for verification.

RESULTS: Compared to normal controls, AD patients showed a significant reduction in the blood monocyte count. In addition, the monocyte count of AD patients was negatively correlated with CSF t-tau and p-tau levels but not with plasma tau levels. In normal people, monocyte count lack correlation with tau levels both in plasma and CSF. Monocyte count were not correlated with CSF Aβ levels in either group but were negatively correlated with CSF tau/Aβ42 levels in the AD group. We had further verified the correlations of monocyte count with CSF tau levels in another cohort.

CONCLUSION: This study suggests that monocytes may play an important role in the clearance of tau protein in the brain.

%B J Alzheimers Dis %V 85 %P 1321-1328 %8 2022 %G eng %N 3 %1 https://www.ncbi.nlm.nih.gov/pubmed/34924377?dopt=Abstract %R 10.3233/JAD-210692 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Cerebrospinal Fluid Amyloid-β Levels are Increased in Patients with Insomnia. %A Chen, Dong-Wan %A Wang, Jun %A Zhang, Li-Li %A Wang, Yan-Jiang %A Gao, Chang-Yue %K Adult %K Aged %K Alzheimer Disease %K Amyloid beta-Peptides %K Biomarkers %K Female %K Humans %K Male %K Middle Aged %K Phosphorylation %K Sleep Initiation and Maintenance Disorders %K tau Proteins %X

Previous studies demonstrate that patients with sleep disorders are at risk of developing Alzheimer's disease (AD), with the mechanism unknown. It is suggested that acute sleep deprivation induces an increase of amyloid-β (Aβ), the major pathological agent in AD, in the cerebrospinal fluid (CSF). In the present study, we recruited 23 patients with chronic insomnia aged between 46 to 67 years and 23 healthy controls aged between 43 to 67 years. We investigated the CSF levels of Aβ and tau, another pathological hallmark in the AD pathogenesis. We found that CSF Aβ42 levels were significantly increased in insomnia patients. However, no significant difference was found in Aβ40, total tau (t-Tau), and phosphorylated tau (p-Tau) between the two groups. Furthermore, we found that CSF Aβ40 and Aβ42 levels are significantly correlated with the sleep quality, as reflected by the Pittsburgh Sleep Quality Index (PSQI) scores. But no significant correlation was found in CSF t-Tau and p-Tau levels with PSQI. Our results indicate that chronic sleep disorders may induce the disruption of Aβ metabolism in the brain, thus increase the risk for developing AD.

%B J Alzheimers Dis %V 61 %P 645-651 %8 2018 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/29278891?dopt=Abstract %R 10.3233/JAD-170032 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Prevention Trials in Alzheimer's Disease: Current Status and Future Perspectives. %A Wang, Jun %A Tan, Lan %A Yu, Jin-Tai %K Alzheimer Disease %K Biomarkers %K Clinical Trials as Topic %K Humans %X

Alzheimer's disease (AD) is the most common form of dementia in the elderly. Over the past 20 years, both pharmacological and lifestyle interventions have been studied for AD prevention, but the overall results have been disappointing. The majority of disappointing results have raised questions and great challenges for the future of AD prevention trials. Ongoing advances in the knowledge of pathogenesis, in the identification of novel targets, in improved outcome measures, and in identification and validation of biomarkers may lead to effective strategies for AD prevention. In this paper, we review the selection of participants and interventions, trial design, outcome assessments, and promising biomarkers in prevention trials, and summarize the lessons learned from completed trials and perspectives from ongoing trials in AD prevention. Selection of optimal participants and interventions, coupled with more refined outcomes and more efficient trial design, may have the capacity to deliver a new era of preventive discovery in this challenging area.

%B J Alzheimers Dis %V 50 %P 927-45 %8 2016 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/26836177?dopt=Abstract %R 10.3233/JAD-150826