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Abstract
Objective: The aim of this study was to investigate whether cognitively preserved monozygotic or dizygotic cotwins of persons with Alzheimer disease (AD) exhibit increased brain amyloid accumulation.
Methods: We performed a cross-sectional carbon-11 labeled 2-(4′-methylaminophenyl)-6-hydroxybenzothiazole (11C)–Pittsburgh compound B (PiB) PET study on 9 monozygotic and 8 dizygotic twin pairs discordant for cognitive impairment as well as on 9 healthy elderly control subjects. 11C-PiB uptake was analyzed with Statistical Parametric Mapping and with region of interest analysis with the region-to-cerebellum ratio as a measure of tracer uptake.
Results: Cognitively preserved monozygotic cotwins of cognitively impaired probands had increased cortical 11C-PiB uptake (117%–121% of control mean) in their temporal and parietal cortices and the posterior cingulate. Cognitively preserved dizygotic subjects did not differ from the controls. Further, the cognitively preserved monozygotic subjects showed similar 11C-PiB uptake patterns as their cognitively impaired cotwins. The cognitively impaired subjects (monozygotic and dizygotic individuals combined) showed typical Alzheimer-like patterns of 11C-PiB uptake.
Conclusions: Genetic factors appear to influence the development of Alzheimer-like β-amyloid plaque pathology. The dissociation between cognitive impairment and brain β-amyloidosis in monozygotic twins implies that there may be important environmental/acquired factors that modulate the relationship between brain amyloidosis and neurodegeneration. AD may be detectable in high-risk individuals in its presymptomatic stage with 11C-PiB PET, but clinical follow-up will be needed to confirm this.
GLOSSARY
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- DZ=
- dizygotic;
- LFC=
- lateral frontal cortex;
- LPI=
- inferior parietal cortex;
- MFC=
- medial frontal cortex;
- MZ=
- monozygotic;
- NEOCORT=
- neocortical region to cerebellum score;
- OCC=
- occipital cortex;
- PC=
- posterior cingulate;
- PiB=
- Pittsburgh compound B;
- PUT=
- putamen;
- ROI=
- region of interest;
- SPM=
- Statistical Parametric Mapping;
- TC=
- temporal cortex;
- WM=
- white matter
Footnotes
Study funding: Supported by the Academy of Finland (projects 205954 and 133193), the Sigrid Jusélius Foundation, clinical grants (EVO) of Turku University Hospital, the Päivi and Sakari Sohlberg Foundation, the Niilo Huolma Fellowship granted by the Medical Faculty of the University of Turku, as well as a grant from the Alzheimer Research Society of Finland. The Finnish Twin Cohort (J.K.) is supported by the Academy of Finland Centre of Excellence in Complex Disease Genetics.
- Received December 4, 2010.
- Accepted April 5, 2011.
- Copyright © 2011 by AAN Enterprises, Inc.
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