Clinical significance of amyloid β positivity in patients with probable cerebral amyloid angiopathy markers

  • Hyemin Jang
  • Young Kyoung Jang
  • Hee Jin Kim
  • David John Werring
  • Jin San Lee
  • Yeong Sim Choe
  • Seongbeom Park
  • Juyeon Lee
  • Ko Woon Kim
  • Yeshin Kim
  • Soo Hyun Cho
  • Si Eun Kim
  • Seung Joo Kim
  • Andreas Charidimou
  • Duk L. Na
  • Sang Won SeoEmail author
Original Article



We investigated the frequency and clinical significance of amyloid β (Aβ) positivity on PET in patients with cerebral amyloid angiopathy (CAA).


We recruited 65 patients who met the modified Boston criteria for probable CAA. All underwent amyloid PET, MRI, APOE genotyping and neuropsychological testing, and we obtained information on MRI markers of CAA and ischemic cerebral small-vessel disease (CSVD). We investigated the CAA/ischemic CSVD burden and APOE genotypes in relation to Aβ positivity and investigated the effect of Aβ positivity on longitudinal cognitive decline.


Among the 65 CAA patients, 43 (66.2%) showed Aβ PET positivity (Aβ+). Patients with Aβ+ CAA had more lobar microbleeds (median 9, interquartile range 2–41, vs. 3, 2–8; P = 0.045) and a higher frequency of cortical superficial siderosis (34.9% vs. 9.1%; P = 0.025), while patients with Aβ− CAA had more lacunes (1, 0–2, vs. 0, 0–1; P = 0.029) and a higher frequency of severe white matter hyperintensities (45.5% vs. 20.9%; P = 0.040). The frequency of ε4 carriers was higher in Aβ+ patients (57.1%) than in Aβ− patients (18.2%; P = 0.003), while the frequency of ε2 carriers did not differ between the two groups. Finally, Aβ positivity was associated with faster decline in multiple cognitive domains including language (P < 0.001), visuospatial function (P < 0.001), and verbal memory (P < 0.001) in linear mixed effects models.


Our findings suggest that a significant proportion of patients with probable CAA in a memory clinic are Aβ− on PET. Aβ positivity in CAA patients is associated with a distinct pattern of CSVD biomarker expression, and a worse cognitive trajectory. Aβ positivity has clinical relevance in CAA and might represent either advanced CAA or additional Alzheimer’s disease neuropathological changes.


Cerebral amyloid angiopathy Amyloid β Amyloid β PET 



S.W.S. receives funding from the Brain Research Program through the National Research Foundation of Korea (2016M3C7A1913844), the Korea Government (MSIP) through the National Research Foundation of Korea grant (2017R1A2B2005081), and the Research of Korea Centers for Disease Control and Prevention (2018-ER6203-01).


This research was funded by the Brain Research Program through the National Research Foundation of Korea (2016M3C7A1913844), the Korea Government (MSIP) through the National Research Foundation of Korea grant (2017R1A2B2005081), and the Research of Korea Centers for Disease Control and Prevention (2018-ER6203-01).

Compliance with ethical standards

Conflicts of interest


Role of the funder

The funders had no role in the design or conduct of the study; in the collection, management, analysis or interpretation of the data; in the preparation, review or approval of the manuscript; or in the decision to submit the manuscript for publication.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

259_2019_4314_MOESM1_ESM.docx (30 kb)
ESM 1 (DOCX 30 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Hyemin Jang
    • 1
    • 2
  • Young Kyoung Jang
    • 1
    • 2
  • Hee Jin Kim
    • 1
    • 2
  • David John Werring
    • 3
  • Jin San Lee
    • 4
  • Yeong Sim Choe
    • 1
  • Seongbeom Park
    • 1
  • Juyeon Lee
    • 5
  • Ko Woon Kim
    • 6
  • Yeshin Kim
    • 7
  • Soo Hyun Cho
    • 1
    • 2
  • Si Eun Kim
    • 8
  • Seung Joo Kim
    • 1
    • 2
  • Andreas Charidimou
    • 9
  • Duk L. Na
    • 1
    • 2
    • 10
  • Sang Won Seo
    • 1
    • 2
    • 10
    Email author
  1. 1.Department of Neurology, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulRepublic of Korea
  2. 2.Neuroscience CenterSamsung Medical CenterSeoulKorea
  3. 3.UCL Stroke Research Centre, Department of Brain Repair and RehabilitationUCL Institute of Neurology and the National Hospital for Neurology and NeurosurgeryLondonUK
  4. 4.Department of NeurologyKyung Hee University School of MedicineSeoulKorea
  5. 5.Department of NeurologyChungnam National University School of MedicineDaejeonKorea
  6. 6.Department of Neurology, Chonbuk National University HospitalChonbuk National University Medical SchoolJeonjuKorea
  7. 7.Department of NeurologyKangwon National University Hospital, Kangwon National University College of MedicineChuncheonKorea
  8. 8.Department of NeurologyInje University College of Medicine, Haeundae Paik HospitalBusanKorea
  9. 9.Department of NeurologyMassachusetts General Hospital Stroke Research Center, Harvard Medical SchoolBostonUSA
  10. 10.Department of Health Sciences and TechnologySAIHST, Sungkyunkwan UniversityGangnam-guRepublic of Korea

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