Apolipoprotein E ε4 and age effects on florbetapir positron emission tomography in healthy aging and Alzheimer disease.
OBJECTIVE
Investigate apolipoprotein E ε4 (APOE4) gene and aging effects on florbetapir F18 positron emission tomography (PET) in normal aging and Alzheimer's disease (AD).


METHODS
Florbetapir F18 PET images were analyzed from 245 participants, 18-92 years of age, from Avid Radiopharmaceutical's multicenter registered trials, including 86 younger healthy control volunteers (yHC), 61 older healthy control volunteers (oHC), 53 mild cognitive impairment (MCI) patients, and 45 AD dementia patients (DAT). Mean florbetapir standard uptake value ratios (SUVRs) were used to evaluate the effects of APOE4 carrier status, older age, and their interaction in each of these groups.


RESULTS
In comparison with non-carriers, the APOE4 carriers in each of the oHC, MCI, and DAT groups had higher mean cortical-to-cerebellar florbetapir SUVRs, patterns of florbetapir PET elevations characteristic of DAT, and a higher proportion meeting florbetapir PET positivity criteria. Only the oHC group had a significant association between mean cortical florbetapir SUVRs and age. In cognitively normal adults, without regards to APOE4 genotype, amyloid began to increase at age 58 (95% confidence interval [CI]: 52.3-63.7), with a predicted typical age of florbetapir positivity occurring around age 71 years. Presence of the APOE4 gene reduced the age of predicted florbetapir positivity in normal aging to around age 56 years, approximately 20 years younger than non-carriers.


CONCLUSIONS
Cerebral amyloid deposition is associated with APOE4 carrier status in older healthy control subjects and symptomatic AD patients, and increases with age in older cognitively normal individuals. Amyloid imaging positivity appears to begin near age 56 years in cognitively intact APOE4 carriers and age 76 years in APOE4 non-carriers.
The Banner Alzheimer's Institute, Phoenix, AZ, USA. Adam.fleisher@bannerhealth.com
Adam S
AS
Fleisher
Kewei
K
Chen
Xiaofen
X
Liu
Napatkamon
N
Ayutyanont
Auttawut
A
Roontiva
Pradeep
P
Thiyyagura
Hillary
H
Protas
Abhinay D
AD
Joshi
Marwan
M
Sabbagh
Carl H
CH
Sadowsky
Reisa A
RA
Sperling
Christopher M
CM
Clark
Mark A
MA
Mintun
Michael J
MJ
Pontecorvo
R Edward
RE
Coleman
P M
PM
Doraiswamy
Keith A
KA
Johnson
Alan P
AP
Carpenter
Daniel M
DM
Skovronsky
Eric M
EM
Reiman
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D000704:Analysis of Variance; D000814:Aniline Compounds; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D001931:Brain Mapping; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D005026:Ethylene Glycols; D006801:Humans; D008609:Mental Status Schedule; D008875:Middle Aged; D049268:Positron-Emission Tomography; D055815:Young Adult
D000814:Aniline Compounds; D053327:Apolipoprotein E4; D005026:Ethylene Glycols; C545186:florbetapir