O2‐02‐06: CEREBROSPINAL‐FLUID‐BASED BIOMARKER EVIDENCE OF AMYLOIDOGENESIS IN DEMENTIA WITH LEWY BODIES DEPENDS UPON APOE‐ε4 CARRIER STATUS

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.