Yonsei Med J.  2018 Aug;59(6):801-805. 10.3349/ymj.2018.59.6.801.

Pathologically Confirmed Cerebral Amyloid Angiopathy with No Radiological Sign in a Patient with Early Onset Alzheimer's Disease

  • 1Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. yeshins@gmail.com
  • 2Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. yl.suh@samsung.com
  • 3Department of Neurology, Kangwon National University Hospital, Kangwon National University College of Medicine, Chuncheon, Korea.


Cerebral amyloid angiopathy (CAA) is associated with perivascular disruption, which is caused by progressive amyloid-beta (Aβ) deposition in vessels. Previous autopsy studies have shown that the prevalence of CAA in Alzheimer's disease (AD) is 70% to 90%. CAA is principally characterized by restricted lobar microbleeds (MBs), which can be detected by gradient-echo T2* (GRE) and susceptibility-weighted imaging (SWI). We herein report on a 62-year-old man who presented with 8 years of memory impairment. The apolipoprotein E (APOE) genotype was ε4/ε4, and a brain GRE performed 28 months before death revealed mild atrophy and no MBs. At autopsy, the patient scored "A3, B3, C3" according to the National Institute on Aging-Alzheimer's Association guidelines; the patient thus exhibited a high level of AD neuropathological changes. Furthermore, immunohistochemical staining for Aβ showed antibody accumulation and severe cerebral amyloid angiopathic changes in numerous vessels with amyloid deposits. Our case suggests that radiological CAA markers, such as cerebral microbleed (CMB) or cerebral superficial siderosis, may not suffice to detect amyloid angiopathy in cerebral vessels. CAA should therefore be considered as a combined pathology in APOE ε4 homozygotes with AD, even if such patients do not exhibit CMB on MRI.


Alzheimer's disease; cerebral amyloid angiopathy; pathology

MeSH Terms

Alzheimer Disease*
Apolipoproteins E
Cerebral Amyloid Angiopathy*
Magnetic Resonance Imaging
Middle Aged
Plaque, Amyloid
Apolipoproteins E


  • Fig. 1 Initial MRI taken 5 years before death. (A) Axial brain MRI fluid-attenuated inversion recovery image demonstrates minimal white matter hyperintensities in the periventricular white matter. (B) There was no abnormal signal on gradient-echo T2* image. MRI, magnetic resonance imaging.

  • Fig. 2 (A–C) Neuronal loss and gliosis in the entorhinal, frontal cortex, and basal nucleus stained by hematoxylin & eosin. (D) Hippocampus of granulovacuolar degeneration (arrows).

  • Fig. 3 (A) Diffuse Aβ deposition in the cerebellum and neocortex stained by immunohistochemistry leading to A3 (Thal phase 5). (B) Tau deposition was also found throughout the neocortex neocortex stained by immunohistochemistry leading to B3 (Braak and Braak stage VI). (C) Neuritic plaques by Bielschowsky silver stain in the frontal and temporal cortex were common, corresponding to CERAD criteria 3. (D) Accumulation of antibodies against Aβ presented in the thickened walls of leptomeningeal and cortical arteries (arrows), as well as arterioles, in immunohistochemical staining. (E) Numerous vessels with amyloid deposits were surrounded with inflammatory infiltration (arrow) in hematoxylin & eosin staining.

  • Fig. 4 The last MRI before death. (A) Axial brain MRI fluid-attenuated inversion recovery image demonstrates increased white matter hyperintensities in the periventricular white matter. (B) There was no interval change on gradient-echo T2* image, compared to initial MRI. MRI, magnetic resonance imaging.


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