Rinsho Shinkeigaku (Clinical Neurology)

Case Report

Sporadic cerebral amyloid angiopathy presenting with dementia and prominent capillary β-amyloid deposition: A case report

Mariko Yamashita, M.D.1), Toru Yamamoto, M.D.1), Masahito Yamada, M.D.2), Souichi Okino, M.D.2) and Takuji Fujita, M.D.1)

1)Department of Neurology, Osaka Saiseikai Nakatsu Hospital
2)Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science

We report a sporadic case of unusual cerebral amyloid angiopathy (CAA) with prominent capillary involvement. A 67-year-old doctor developed gait disturbance, resting tremor and rigidity. He was diagnosed to have Parkinson's disease, for which the treatment with levodopa was effective. Four years later he began to exhibit progressive cognitive decline and behavioral abnormalities consisting of hallucination and agitation. Subsequently, his condition steadily worsened and became bedridden with severe dementia, and he died eight years after the disease onset. During the clinical course, there had been no episode of stroke. Postmortem examinations revealed the typical pathology of Parkinson's disease with frequent cortical Lewy bodies in the amygdala. The most striking pathological feature of this patient was widespread CAA where prominent β-amyloid (Aβ) deposition was observed in the capillaries of the neocortex, most pronouncedly in the occipital lobe, as well as leptomeningeal and cerebral medium-sized and small vessels. Further, perivascular plaques were found in half of the amyloid-laden capillaries. Tau-positive dystrophic neurites were only sparsely detectable within a few perivascular plaques. Despite the severe Aβ pathology, there was no microaneurysmal dilatation, fibrinoid necrosis or vascular occlusion. There was only one small ischemic lesion in the brain. The cerebral white matter was unremarkable. Senile plaques of neuritic type and neurofibrillary tangles were mostly limited to the hippocampal regions and, to a lesser degree, in the amygdaloid nucleus, which did not meet the neuropathological criteria of Alzheimer's disease. On the gene analyses, his apolipoprotein E (ApoE) genotyping was verified to be heterozygous ε3/ε4, and no mutation was seen in exons 16 and 17 of the amyloid precursor protein gene.

Severe Aβ capillary angiopathy as seen in our patient is exceptional in sporadic CAA. Further, Aβ angiopathy of this patient was notable in the absence of an associated cerebrovascular disease despite prominent Aβ deposition in the vessel walls. Regarding the development of his severe dementia, the limbic pathology of Lewy body disease might be one of the potential causes, but Aβ angiopathy appears more likely because of its severity. We speculate that widespread Aβ deposition disregulates the blood-brain barrier of the capillaries leading to a disturbance of the microcirculation throughout the cerebral cortex without obvious ischemic disintegration of the neuropil. We should take into consideration that Aβ angiopathy can present as progressive dementia without cerebrovascular disease.

(CLINICA NEUROL, 42: 530－535, 2002)
key words: apolipoprotein E genotyping, β-amyloid protein, capillary, cerebral amyloid angiopathy, dementia

(Received: 24-Apr-02)