Abstract
Cerebral amyloid angiopathy (CAA), the major etiology of spontaneous lobar intracerebral hemorrhage (ICH), is caused by deposition of β-amyloid (Aβ) proteins in the leptomeningeal and cortical small vessels of the brain. In addition to brain MRI which shows a characteristic strictly lobar distribution of hemorrhagic lesions, molecular imaging tool such as amyloid PET has provided the perspective of vascular amyloid load and amyloid distribution in CAA patients. Our group in National Taiwan University Hospital has established the cohort of spontaneous ICH patients with comprehensive neuroimaging study since 2014, with special focus on understanding the underlying small vessel subtype in ICH. We also aim to use this cohort to delineate the potential pathogenic mechanisms of CAA.
We first identified CAA in patients presenting with mixed lobar and deep hemorrhages, and confirmed these patients harbor detrimental vascular outcome in the long-term, reinforcing its clinical significance in ICH population. We then expanded the current knowledge of CAA neuroimaging spectrum, showing that CAA can involve not only supratentorial, but also infratentorial small vessels in superficial cerebellar area. By showing the association between CAA and lacunar infarct, we further extended the parenchymal injury of CAA from hemorrhage to cerebral ischemia. With the advantage of quantitative data in amyloid PET, we investigate the association between markers of cerebral drainage system dysfunction and amyloid depositions in CAA, which shows a close relationship between vascular amyloid amount and enlarged perivascular spaces in centrum-semiovale, decreased cerebrospinal fluid drainage function or even cerebral venous insufficiency.
Despite of its advantage in research, amyloid PET is not able to provide adequate diagnostic utility in CAA, especially in differentiating CAA from another Aβ-related disorders, the Alzheimer’s disease. Our study with combined amyloid and tau scans suggests that there is a great overlap between CAA and AD. Although it appears that the whole amyloid amount is significantly lower in CAA group than in AD group, the role of applying it in diagnosing individual patient is still very limited. Future work should be emphasized on developing tracers that is more specific to bind vascular amyloid plaque and to explore its roles in clinical practice, including as a cognitive prognostic marker or as a therapeutic outcome marker in clinical trials.
Hsin-Hsi Tsai, Ph.D.
Department of Neurology
National Taiwan University College of Medicine
Hsin-Hsi Tsai, Ph.D.
Dr. Hsin-Hsi Cynthia Tsai is the clinical assistant professor in Neurology department in National Taiwan University College of Medicine. She is also the neurology attending physician in National Taiwan University Hospital. Her research interests and clinical specialty mainly focus on diagnosis and prognosis in intracerebral hemorrhage, novel therapeutics for intracerebral hemorrhage, as well as molecular and functional imaging in cerebral amyloid angiopathy, cerebral small vessel disease and vascular.
Education
2017.09-2021.06: PhD, Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University
2005.09-2012.06: MD, College of Medicine, National Taiwan University
Publications (Selected)
1. Chen SJ, *Tsai HH (Corresponding author), Lo YL, Chen YF, Tang SC, Jeng JS, Tsai LK. Interaction Between Cerebral Small Vessel Disease, Blood Pressure and Remote Ischemic Lesions in Acute Spontaneous Intracerebral Hemorrhage, European Stroke Journal online ahead of print.
2. Lee BC, *Tsai HH (Corresponding author), Liu CJ, Chen YF, Tsai LK, Jeng JS, Yen RF. Cerebral Venous Reflux and Cerebral Amyloid Angiopathy: An Magnetic Resonance Imaging/Positron Emission Tomography Study. Stroke. 2023 Apr;54(4):1046-1055.
3. Tsai HH, Lee BC, Chen YF, Jeng JS, Tsai LK. Cerebral Venous Reflux and Dilated Basal Ganglia Perivascular Space in Hypertensive Intracerebral Hemorrhage. J Stroke. 2022;24(3):363-371.
4. Tsai HH, Hsieh YC, Lin JS, Kuo ZT, Ho CY, Chen CH, Chang CF. Functional investigation of meningeal lymphatic system in experimental intracerebral hemorrhage. Stroke. 2022 Mar;53(3):987-998.
5. Tsai HH, Chen YF, Yen RF, Lo YL, Yang KC, Jeng JS, Tsai LK, Chang CC. Plasma Soluble TREM2 is Associated with White Matter Lesions Independent of Amyloid and Tau. Brain. 2021 Dec 16;144(11):3371-3380.
6. Tsai HH, Pasi M, Tsai LK, Huang CC, Chen YF, Lee BC, Yen RF, Gurol ME, Jeng JS. Centrum-semiovale Perivascular Space and Amyloid Deposition in Spontaneous Intracerebral Hemorrhage, Stroke. 2021 Jul;52(7):2356-2362.
7. Tsai HH, Chen SJ, Tsai LK, Pasi M, Lo YL, Chen YF, Tang SC, Jeng JS. Long Term Vascular Outcomes in Patients with Mixed Location Intracerebral Hemorrhage And Microbleeds, Neurology. 2021 Feb 16;96(7):e995-e1004.
8. Tsai HH, Pasi M, Tsai LK, Chen YF, Chen YW, Tang SC, Gurol ME, Yen RF, Jeng JS. Superficial Cerebellar Microbleeds and Cerebral Amyloid Angiopathy: A Magnetic Resonance Imaging/Positron Emission Tomography Study. Stroke. 2020 Jan;51(1):202-208.
9. Tsai HH, Pasi M, Tsai LK, Chen YF, Lee BC, Tang SC, Fotiadis P, Huang CY, Yen RF, Jeng JS, Gurol ME. Microangiopathy underlying mixed-location intracerebral hemorrhages/microbleeds A PiB-PET study. Neurology. 2019 Feb 19;92(8):e774-e781.
10. Tsai HH, Kim JS, Jouvent E, Gurol ME. Updates on Prevention of Hemorrhagic and Lacunar Strokes. J Stroke. 2018 May;20(2):167-179.
11. Tsai HH, Pasi M, Tsai LK, Chen YF, Lee BC, Tang SC, Fotiadis P, Huang CY, Yen RF, Gurol ME, Jeng JS. Distribution of Lacunar Infarcts in Asians with Intracerebral Hemorrhage: An MRI and Amyloid PET Study. Stroke. 2018 Jun;49(6):1515-1517.