Elsevier

Biological Psychiatry

Volume 68, Issue 10, 15 November 2010, Pages 879-884
Biological Psychiatry

Archival Report
Progression of Cerebral Amyloid Load Is Associated with the Apolipoprotein E ε4 Genotype in Alzheimer's Disease

https://doi.org/10.1016/j.biopsych.2010.05.013Get rights and content

Background

Pittsburgh Compound B ([11C] PiB) is a specific positron emission tomography (PET) marker of cerebral amyloid deposits. Only few data have been published on in vivo longitudinal changes of amyloid load in Alzheimer's disease (AD) patients, with conflicting results. Therefore, little is known about the factors that influence these changes.

Methods

A group of 24 patients with probable AD diagnosed by combining established clinical criteria with an AD-typical pattern in [18F] fluoro-deoxy-glucose PET underwent [11C] PiB-PET examinations at baseline and after 24 months. The difference of amyloid load between the two examinations and the association with clinical and neurobiological variables was examined with a regions-of-interest approach and voxel-based analyses.

Results

Cerebral [11C] PiB uptake ratio increased significantly by an annual rate of 3.92%. Although the increase occurred in all parts of the neocortex, no increase was detected in the archipallium. The increase was gene-dose-dependent (analysis of variance p = .012) to the number of apolipoprotein E ε4 alleles. Progression of dementia symptoms was correlated to the [11C] PiB increase in numerous regions associated with cognition.

Conclusions

The results of this study indicate that a significant increase of amyloid deposition occurs in patients with AD during a relatively short interval of its clinical course. The rate of amyloid aggregation rate is closely associated with the apolipoprotein E genotype, which might be important for the evaluation of antiamyloid drug treatment effects. The present study further emphasizes the value of amyloid-plaque imaging as a marker of disease progression and as a potential surrogate marker to be used in antiamyloid drug trials.

Section snippets

Patient Recruitment, Inclusion, and Exclusion Criteria

Patients were recruited from the research outpatient unit for cognitive disorders at the Department of Psychiatry, Klinikum rechts der Isar, Technische Universitaet, Muenchen, Munich, Germany. They had been referred for the diagnostic evaluation of cognitive impairment by general practitioners, neurologists, psychiatrists, or other institutions and had undergone a standardized diagnostic procedure.

The diagnostic work-up included an interview with the patient and an informant; medical,

Patients

Informed consent was obtained from 42 patients. Of these, 18 did not participate in the follow-up examination and were excluded from the analysis. Four patients had died, five patients had become too ill to undergo PET or MRI examinations, and nine patients or their caregivers had withdrawn consent. The remaining 24 patients were included in the present study. The demographic data of the sample are provided in Table 1. All patients fulfilled diagnostic criteria of probable AD. Three patients

Discussion

In the current study we analyzed the change of C/cv [11C] PiB uptake ratios during a mean interval of 26.6 months in a sample of 24 patients with AD who were diagnosed clinically and with [18F] FDG-PET. The [11C] PiB uptake, which is an in vivo marker of cerebral amyloid deposition, showed a statistically significant increase within this relatively short time interval.

Tracer uptake at baseline and increased uptake at follow-up was most prominent in the neocortex, whereas relatively low baseline

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