Effects of the active amyloid beta immunotherapy CAD106 on PET measurements of amyloid plaque deposition in cognitively unimpaired APOE ε4 homozygotes.
Alzheimers Dement
; 20(3): 1839-1850, 2024 03.
Article
in En
| MEDLINE
| ID: mdl-38145469
ABSTRACT
INTRODUCTION:
Alzheimer's Prevention Initiative Generation Study 1 evaluated amyloid beta (Aß) active immunotherapy (vaccine) CAD106 and BACE-1 inhibitor umibecestat in cognitively unimpaired 60- to 75-year-old participants at genetic risk for Alzheimer's disease (AD). The study was reduced in size and terminated early. Results from the CAD106 cohort are presented.METHODS:
Sixty-five apolipoprotein E ε4 homozygotes with/without amyloid deposition received intramuscular CAD106 450 µg (n = 42) or placebo (n = 23) at baseline; Weeks 1, 7, 13; and quarterly; 51 of them had follow-up Aß positron emission tomography (PET) scans at 18 to 24 months.RESULTS:
CAD106 induced measurable serum Aß immunoglobulin G titers in 41/42 participants, slower rates of Aß plaque accumulation (mean [standard deviation] annualized change from baseline in amyloid PET Centiloid -0.91[5.65] for CAD106 versus 8.36 [6.68] for placebo; P < 0.001), and three amyloid-related imaging abnormality cases (one symptomatic).DISCUSSION:
Despite early termination, these findings support the potential value of conducting larger prevention trials of Aß active immunotherapies in individuals at risk for AD. HIGHLIGHTS This was the first amyloid-lowering prevention trial in persons at genetic risk of late-onset Alzheimer's disease (AD). Active immunotherapy targeting amyloid (CAD106) was tested in this prevention trial. CAD106 significantly slowed down amyloid plaque deposition in apolipoprotein E homozygotes. CAD106 was generally safe and well tolerated, with only three amyloid-related imaging abnormality cases (one symptomatic). Such an approach deserves further evaluation in larger AD prevention trials.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Amyloid beta-Peptides
/
Alzheimer Disease
Limits:
Aged
/
Humans
/
Middle aged
Language:
En
Journal:
Alzheimers Dement
Year:
2024
Document type:
Article