O2‐02‐06: CEREBROSPINAL‐FLUID‐BASED BIOMARKER EVIDENCE OF AMYLOIDOGENESIS IN DEMENTIA WITH LEWY BODIES DEPENDS UPON APOE‐ε4 CARRIER STATUS
Alzheimer's & Dementia(2019)
摘要
Amyloidogenesis may cause earlier onset of dementia with Lewy bodies (DLB) as well as Alzheimer's dementia (AD), whereas the angiotensin-converting enzyme (ACE-1) is an amyloid-β-degrading enzyme. Consecutive outpatients with probable DLB (fourth consensus report of the DLB Consortium) were paired with outpatients with late-onset AD (National Institute on Aging – Alzheimer's Association) by gender, Clinical Dementia Rating (CDR) and Mini-Mental State Examination scores, and with cognitively healthy controls by gender and age (±1 year). Genotyping for rs7412 and rs429358 (APOE) was undertaken with TaqMan® Real-Time PCR technology. Cerebrospinal fluid concentrations of amyloid (Aβ42/Aβ40/Aβ38), ACE-1, tau and phospho-tau Thr181 were assessed by enzyme-linked immunosorbent assays, significance at p<0.05. Overall, 27 participants with DLB (78.48±9.0 years-old, CDR sum-of-boxes 10.96±3.8, eleven APOE-ε4 carriers) were paired with 27 participants with AD (81.00±5.8 years-old, CDR sum-of-boxes 10.44±3.9, twelve APOE-ε4 carriers) and 27 controls (78.48±8.7 years-old, CDR sum-of-boxes 0.30±0.8, four APOE-ε4 carriers); two thirds were women. For APOE-ε4 carriers: Aβ42/Aβ40 0.08±0.0 for DLB, 0.06±0.0 for AD, 0.08±0.0 for controls, p=0.898; Aβ42/Aβ38 0.23±0.1 for DLB, 0.19±0.1 for AD, 0.50±0.5 for controls, p=0.341; tau/phospho-tau 4.37±5.7 for DLB, 4.01±4.0 for AD, 1.74±0.3 for controls, p=0.235; ACE-1 levels (ng/ml) 2.32±1.5 for DLB, 1.94±1.4 for AD, 2.51±2.0 for controls, p=0.779. For APOE-ε4 non-carriers: Aβ42/Aβ40 0.10±0.1 for DLB, 0.07±0.0 for AD, 0.08±0.0 for controls, p=0.274; Aβ42/Aβ38 0.36±0.2 for DLB, 0.20±0.1 for AD, 0.30±0.1 for controls, p=0.009; tau/phospho-tau 1.90±1.2 for DLB, 4.33±9.0 for AD, 2.47±1.4 for controls, p=0.101; ACE-1 levels (ng/ml) 2.05±1.8 for DLB, 2.34±1.3 for AD, 2.32±1.7 for controls, p=0.596. Use of ACE inhibitors did not affect ACE-1 levels. Most patients were in earlier dementia stages, translating into many non-significant comparisons. Aβ42/Aβ38 was significantly higher only for APOE-ε4 non-carriers with DLB, whereas Aβ42/Aβ40 and Aβ42/Aβ38 were lower for APOE-ε4 carriers with DLB than for APOE-ε4 non-carriers with DLB; tau pathology in DLB followed tau pathology in AD more closely for APOE-ε4 carriers. ACE-1 levels were non-significantly higher only for APOE-ε4 non-carriers with AD. Our results suggest that amyloidogenesis in DLB follows that in AD when patients are APOE-ε4 carriers, but confirmation in larger samples is required. Supported by FAPESP grant #2015/10109-5.
更多查看译文
AI 理解论文
溯源树
样例
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要