Recurrent Lobar Hemorrhages and Multiple Cortical Superficial Siderosis in a Patient of Alzheimer's Disease With Homozygous APOE ε2 Allele Presenting Hypobetalipoproteinemia and Pathological Findings of 18F-THK5351 Positron Emission Tomography: A Case Report

Abstract

In Alzheimer's disease, the apolipoprotein E gene (APOE) ε2 allele is a protective genetic factor, whereas the APOE ε4 allele is a genetic risk factor. However, both the APOE ε2 and the APOE ε4 alleles are genetic risk factors for lobar intracerebral hemorrhage. The reasons for the high prevalence of lobar intracerebral hemorrhage and the low prevalence of Alzheimer's disease with the APOE ε2 allele remains unknown. Here, we describe the case of a 79-year-old Japanese female with Alzheimer's disease, homozygous for the APOE ε2 allele. This patient presented with recurrent lobar hemorrhages and multiple cortical superficial siderosis. The findings on the 11C-labeled Pittsburgh Compound B-positron emission tomography (PET) were characteristic of Alzheimer's disease. 18F-THK5351 PET revealed that the accumulation of 18F-THK 5351 in the right pyramidal tract at the pontine level, the cerebral peduncle of the midbrain, and the internal capsule, reflecting the lesions of the previous lobar intracerebral hemorrhage in the right frontal lobe. Moreover, 18F-THK5351 accumulated in the bilateral globus pallidum, amygdala, caudate nuclei, and the substantia nigra of the midbrain, which were probably off-target reaction, by binding to monoamine oxidase B (MAO-B). 18F-THK5351 were also detected in the periphery of prior lobar hemorrhages and a cortical subarachnoid hemorrhage, as well as in some, but not all, areas affected by cortical siderosis. Besides, 18F-THK5351 retentions were observed in the bilateral medial temporal cortices and several cortical areas without cerebral amyloid angiopathy or prior hemorrhages, possibly where tau might accumulate. This is the first report of a patient with Alzheimer's disease, carrying homozygous APOE ε2 allele and presenting with recurrent lobar hemorrhages, multiple cortical superficial siderosis, and immunohistochemically vascular amyloid β. The 18F-THK5351 PET findings suggested MAO-B concentrated regions, astroglial activation, Waller degeneration of the pyramidal tract, neuroinflammation due to CAA related hemorrhages, and possible tau accumulation.

Superficial siderosis: comparison of two cases indicates two distinct diagnostic entities. Illustrative cases

“…Additionally, lobar SS demonstrates a strong correlation between amyloid angiopathy and AD, according to the literature. 7,14,16 This would be the most likely reason for the superficial siderosis in the left occipital lobe and would represent a relatively ominous finding in this patient. The pattern of siderosis in her case does not fit the distribution typically seen in patients with occult leakage of blood into the CSF, in which the spinal cord and cerebellum are usually diffusely coated with siderosis in a relatively symmetrical fashion.…”

“…The patient was diagnosed with AD because of the CSF biomarkers such as Ab42, Ab40, and tau protein found through lumbar puncture. 14,15 Other signs consistent with AD include MRI indicating cerebral atrophy, which was seen in case 2, especially in the left hemisphere.…”

Neurobiological correlation between phosphorylated tau and mood symptoms in memory clinic patients

“…To identify the APOE gene, we purified genomic DNA from lymphocytes collected from peripheral blood samples of each patient. For analysis of APOE allele polymorphisms, purified genomic DNA samples were examined as previously described 42 . The APOE protein was measured by a contracted laboratory (LSI Medience Corp., Tokyo, Japan).…”

“…For analysis of APOE allele polymorphisms, purified genomic DNA samples were examined as previously described. 42 The APOE protein was measured by a contracted laboratory (LSI Medience Corp., Tokyo, Japan). We dichotomised APOE by the presence or absence of ε4, denoted by the terms ε4 carrier and non-carrier, respectively.…”