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Original research
The heritability of amyloid burden in older adults: the Older Australian Twins Study
  1. Rebecca Koncz1,2,
  2. Anbupalam Thalamuthu1,
  3. Wei Wen1,
  4. Vibeke S Catts1,
  5. Vincent Dore3,4,
  6. Teresa Lee1,5,
  7. Karen A Mather1,6,
  8. Melissa J Slavin1,
  9. Eva A Wegner7,8,
  10. Jiyang Jiang1,
  11. Julian N Trollor1,9,
  12. David Ames10,11,
  13. Victor L Villemagne3,12,
  14. Christopher C Rowe3,13,
  15. Perminder S Sachdev1,5
  16. on behalf of the Older Australian Twins Study collaborative team
  1. 1 Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Sydney, Sydney, New South Wales, Australia
  2. 2 Specialty of Psychiatry, Faculty of Medicine and Health, The University of Sydney, Concord, New South Wales, Australia
  3. 3 Department of Molecular Imaging and Therapy, Austin Health, Heidelberg, Victoria, Australia
  4. 4 The Australian e-Health Research Centre, CSIRO Health and Biosecurity, Parkville, Victoria, Australia
  5. 5 Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, New South Wales, Australia
  6. 6 Neuroscience Research Australia, Randwick, New South Wales, Australia
  7. 7 Department of Nuclear Medicine and PET, Prince of Wales Hospital, Randwick, New South Wales, Australia
  8. 8 Prince of Wales Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, New South Wales, Australia
  9. 9 Department of Developmental Disability Neuropsychiatry, School of Psychiatry, UNSW Sydney, Sydney, New South Wales, Australia
  10. 10 Academic Unit for Psychiatry of Old Age, University of Melbourne, Kew, Victoria, Australia
  11. 11 National Ageing Research Institute, Parkville, Victoria, Australia
  12. 12 Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia
  13. 13 Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia
  1. Correspondence to Dr Rebecca Koncz, Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Sydney, Sydney, New South Wales, Australia; r.koncz{at}unsw.edu.au

Abstract

Objective To determine the proportional genetic contribution to the variability of cerebral β-amyloid load in older adults using the classic twin design.

Methods Participants (n=206) comprising 61 monozygotic (MZ) twin pairs (68 (55.74%) females; mean age (SD): 71.98 (6.43) years), and 42 dizygotic (DZ) twin pairs (56 (66.67%) females; mean age: 71.14 (5.15) years) were drawn from the Older Australian Twins Study. Participants underwent detailed clinical and neuropsychological evaluations, as well as MRI, diffusion tensor imaging (DTI) and amyloid PET scans. Fifty-eight participants (17 MZ pairs, 12 DZ pairs) had PET scans with 11Carbon-Pittsburgh Compound B, and 148 participants (44 MZ pairs, 30 DZ pairs) with 18Fluorine-NAV4694. Cortical amyloid burden was quantified using the centiloid scale globally, as well as the standardised uptake value ratio (SUVR) globally and in specific brain regions. Small vessel disease (SVD) was quantified using total white matter hyperintensity volume on MRI, and peak width of skeletonised mean diffusivity on DTI. Heritability (h 2) and genetic correlations were measured with structural equation modelling under the best fit model, controlling for age, sex, tracer and scanner.

Results The heritability of global amyloid burden was moderate (0.41 using SUVR; 0.52 using the centiloid scale) and ranged from 0.20 to 0.54 across different brain regions. There were no significant genetic or environmental correlations between global amyloid burden and markers of SVD.

Conclusion Amyloid deposition, the hallmark early feature of Alzheimer’s disease, is under moderate genetic influence, suggesting a major environmental contribution that may be amenable to intervention.

  • amyloid
  • cerebrovascular disease
  • genetics

Data availability statement

Data are available upon request. Data related to this study can be made available upon reasonable request by contacting the Older Australian Twins Study, Centre for Healthy Brain Ageing, UNSW Sydney (https://cheba.unsw.edu.au/research-projects/older-australian-twins-study). A project application including a methodologically sound proposal will need to be submitted by interested researchers for review by the OATS Investigators.

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Data availability statement

Data are available upon request. Data related to this study can be made available upon reasonable request by contacting the Older Australian Twins Study, Centre for Healthy Brain Ageing, UNSW Sydney (https://cheba.unsw.edu.au/research-projects/older-australian-twins-study). A project application including a methodologically sound proposal will need to be submitted by interested researchers for review by the OATS Investigators.

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Footnotes

  • Contributors PSS, CCR, MJS, JNT and TL contributed to the study design. VSC coordinated the study and data collection. EAW led the amyloid PET scan collection in Sydney. VD, CCR and VLV collected the amyloid PET images in Melbourne and processed all amyloid PET images. WW and JJ processed the MRI and DTI images. KM completed the genotyping. AT lead the data analysis. RK completed the literature review, cleaned the data, contributed to the analysis, and drafted the manuscript. All authors contributed to the interpretation of results, reviewed and critically revised the manuscript, and approved the final version for submission. RK is the guarantor for this work.

  • Funding The OATS study has been funded by a National Health & Medical Research Council (NHMRC) and Australian Research Council (ARC) Strategic Award Grant of the Ageing Well, Ageing Productively Programme (ID No. 401162); NHMRC Project Grants (ID 1045325 and 1085606); and NHMRC Programme Grants (ID No. 568 969 and 1093083). DNA was extracted by Genetic Repositories Australia, which was funded by the NHMRC Enabling Grant 401 184. OATS genotyping was partly funded by a Commonwealth Scientific and Industrial Research Organisation Flagship Collaboration Fund Grant. This research was facilitated through Twins Research Australia, a national resource in part supported by a Centre for Research Excellence Grant (ID: 1079102) from the National Health and Medical Research Council.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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