van Dyck CH, Brück A, Barcelos NM, Benincasa AL, Planeta-Wilson B, MacAvoy MG, Ding YS, Gelernter J, Carson RE.
Amyloid-ß burden and neuropsychological test performance in cognitively normal first-degree relatives at varying genetic risk for Alzheimer’s disease.
Human Amyloid Imaging 2010 Meeting Abstracts. 2010 April 9;
In Alzheimer's disease (AD) there is strong evidence that brain amyloid deposition precedes the emergence
of dementia by many years. In addition, a greater accumulation of amyloid in the postmortem brain has been
demonstrated in people who carry the major genetic risk factor for AD – APOE-ε4. This study investigated the
relationship between APOE-ε4 genotype, amyloid deposition, and neuropsychological test performance in presymptomatic
individuals at varying genetic risk for AD.
Methods: Cognitively normal subjects (n=270) aged 50-69, with a first-degree family history for AD, were genetically
screened to select three groups: APOE genotype ε4ε4 (n=9), ε3ε4 (n=10), and ε3ε3 (n=10), matched for age, sex,
and education. Subjects were then studied with ([11C]PiB) PET, MRI, and neuropsychological testing. PET and MR
images were co-registered for application of an ROI template (AAL for SPM2) to generate regional time-activity
curves with cerebellum as reference region. Parametric BPND images are then generated using SRTM2 such that
BPND=0 reflects no specific binding. BPND was computed for a mean cortical ROI consisting of frontal, posterior
cingulate-precuneus, and lateral temporal ROIs.
Results: APOE-ε4 carriers demonstrated significantly greater BPND (0.37±0.20) in comparison to non-carriers
(0.21±0.09; t=2.37, p=0.025), with no dosage effect between ε4ε4 and ε3ε4 groups. There was no significant effect
of APOE genotype on neuropsychological test performance. When associations between mean cortical [11C]PiB
BPND and neuropsychological test performance were examined, there was some tendency for [11C]PiB binding
to be correlated with measures of episodic memory: CVLT recognition hits (r=-0.47, p=0.02), CVLT free-delayed
recall (r=-0.38, p=0.07), Visual Reproductions I (r=0.52, p=0.01).
Conclusions: These results confirm and extend observations by Reiman et al, 2009, but in a somewhat younger
sample (mean age 60 vs 65). Additional research is necessary to determine the predictive value and functional
consequences of brain amyloid deposition in asymptomatic individuals at risk for AD.