Objective: To assess whether angiotensin-converting enzyme (ACE) inhibitors modulate associations of biofluid concentrations and activity of ACE with motor and non-motor experiences in dementia with Lewy bodies (DLB) compared with Alzheimer’s dementia (AD) and cognitively healthy people.

Background: Amyloidogenesis is pathogenically important in DLB as well as in AD. ACE inhibitors are neuroprotective for patients with AD, possibly by way of central cholinergic effects or boosted neprilysin activity, or by way of peripheral enhancement of insulin sensitivity.

Methods: 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 workgroups) by gender, Clinical Dementia Rating (CDR) and Mini-Mental State Examination scores, and with cognitively healthy controls by gender and age (±1 year). Genotyping was undertaken with TaqMan® Real-Time Polymerase Chain Reactions for APOE (rs7412 & rs429358), and with Polymerase Chain Reactions for ACE I/D. Cerebrospinal fluid (CSF) concentrations of Aβ40 and ACE were assessed by ELISA, whereas CSF and plasma activity of ACE were measured by a fluorimetric method, and correlated with the Schwab and England Scale (S&E), the Movement Disorder Society – Unified Parkinson’s Disease Rating Scale (MDS-UPDRS parts I/II/III), and the Hoehn and Yahr stages (H&Y).

Results: Overall, 27 participants with DLB (78.48±9.0 years-old, CDR sum-of-boxes 11.00±3.8, 11 APOE-ε4 carriers, 7 users of ACE inhibitors) were paired with 27 participants with AD (81.00±5.8 years-old, CDR sum-of-boxes 10.46±3.9, 12 APOE-ε4 carriers, 9 users of ACE inhibitors) and 27 controls (78.48±8.7 years-old, CDR sum-of-boxes 0.41±0.8, 4 APOE-ε4 carriers, 5 users of ACE inhibitors). Associations for APOE-ε4 carriers (p<0.0001): plasma ACE activity associated with S&E in DLB and AD, minimized by the use of ACE inhibitors. Associations for APOE-ε4 non-carriers (p<0.0001): CSF ACE activity associated with MDS-UPDRS-I in DLB and AD, and inversely associated with MDS-UPDRS-II and MDS-UPDRS-III and H&Y in DLB; plasma ACE activity inversely associated with S&E in AD and with MDS-UPDRS-I in DLB; all biofluid ACE activity effects were minimized by the use of ACE inhibitors; CSF ACE/Aβ40 ratio inversely associated with S&E and H&Y in AD. The ACE I/D polymorphism had no effects over any biofluid variables.

Conclusions: ACE inhibitors had neuroprotective effects mostly for APOE-ε4 non-carriers with AD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/angiotensin-converting-enzyme-inhibitors-are-neuroprotective-regarding-apoe-mediated-motor-and-non-motor-experiences-for-alzheimers-dementia-but-not-for-dementia-with-lewy-bodies/