Abstract Details

Title Biofluid Activity and Levels of the Angiotensin-converting Enzyme Are Surrogates for Diverse Cerebrospinal Fluid Amyloid-beta Effects in Dementia with Lewy Bodies and Alzheimer’s Dementia

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P6 - Poster Session 6 (8:00 AM-9:00 AM)

Poster/Presentation
Number 9-001

Objective

To investigate if biofluid activity and levels of the angiotensin-converting enzyme (ACE-1) are associated with other biomarkers.

Background

ACE-1 is an amyloid-beta-degrading enzyme, and might be a useful biomarker of brain amyloid-beta load.

Design/Methods Consecutive outpatients with probable dementia with Lewy bodies (fourth consensus report of the DLB Consortium) were paired with outpatients with late-onset Alzheimer’s dementia (AD, National Institute on Aging – Alzheimer’s Association) by sex, Clinical Dementia Rating (CDR) and Mini-Mental State Examination scores, and with cognitively healthy controls by sex and age (±1 year). APOE genotyping (rs7412&rs429358) was undertaken with TaqMan® Real-Time PCR technology. Cerebrospinal fluid (CSF) amyloid-beta (Aβ₄₂,Aβ₄₀,Aβ₃₈), ACE-1, tau and phospho-tau Thr₁₈₁ were quantified by immunoassays, whereas CSF and plasma ACE-1 activities were measured by way of a fluorescence method, significant p<0.05.

Results Participants with DLB (n=27;78.48±9.0years-old;CDR sum-of-boxes 10.96±3.8;eleven APOE-ε4+) were paired with participants with AD (n=27;81.00±5.8years-old;CDR sum-of-boxes 10.44±3.9;twelve APOE-ε4+) and controls (n=27;78.48±8.7years-old;CDR sum-of-boxes 0.30±0.8;four APOE-ε4+); two thirds were women. CSF ACE-1 activity was directly associated with CSF ACE-1 levels (p<0.0001) and with plasma ACE-1 activity (p<0.0001), no differences among participants. Use of ACE inhibitors did not affect CSF ACE-1 levels. For all, CSF ACE-1 levels and activity, as well as plasma ACE-1 activity, were inversely associated with the Aβ₄₂/Aβ₄₀ ratio (p<0.0001). Only for patients with DLB, CSF ACE-1 levels and activity, as well as plasma ACE-1 activity, were associated with the Aβ₄₂/Aβ₃₈ ratio (p<0.0001), whereas these same associations were inverse for other participants (p<0.0001). For all, CSF ACE-1 levels and activity, as well as plasma ACE-1 activity, were associated with the tau/phospho-tau Thr₁₈₁ ratio (p<0.01), though less significantly in patients with AD. All significant associations were independent of APOE-ε4 carriership.

Conclusions

Biofluid activity and CSF levels of the ACE-1 are surrogates for CSF amyloid-beta levels and tauopathy, and might help differentiate dementia with Lewy bodies from Alzheimer’s dementia.

Authors/Disclosures
Fabricio F. De Oliveira, MD, PhD, BBA, MSc, FAAN, FAAN (Elysian Clinic) PRESENTER	Dr. De Oliveira has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Gerson Lehrman Group. Dr. De Oliveira has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Atheneum Partners. Dr. De Oliveira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Guidepoint. Dr. De Oliveira has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lionbridge. Dr. De Oliveira has received personal compensation in the range of $0-$499 for serving as a Consultant for Coleman. Dr. De Oliveira has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. De Oliveira has received personal compensation in the range of $0-$499 for serving as a Neurology® Video Journal Club Presenter with ��ɫ��.
Marjorie Miraldo	No disclosure on file
Eduardo Castro-Neto	No disclosure on file
Sandro Almeida	No disclosure on file
Sandro Luiz de Andra Matas	No disclosure on file
Paulo Bertolucci	No disclosure on file
Maria Naffah-Mazzacoratti	No disclosure on file

��ɫ����

��ɫ����

��ɫ��

��ɫ��