Cerebral amyloid angiopathy in the aged

Yamada, Masahito; Tsukagoshi, Hiroshi; Otomo, E; Hayakawa, Michio

doi:10.1007/bf00314080

Cited by 177 publications

(140 citation statements)

References 32 publications

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“…The major component of NFTs is the microtubule-associated protein tau. It has been reported that ␤-amyloid, a peptide observed as an aggregated form in senile plaques of AD (5), cannot exhibit neurotoxicity and induce neurodegeneration without the existence of tau (6,7). As demonstrated in these studies, tau is considered to play a crucial role in inducing neurodegeneration.…”

mentioning

confidence: 88%

GSK-3β Directly Phosphorylates and Activates MARK2/PAR-1

Kosuga¹,

Tashiro²,

Kajioka

et al. 2005

Journal of Biological Chemistry

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In Alzheimer disease (AD), the microtubule-associated protein tau is found hyperphosphorylated in paired helical filaments. Among many phosphorylated sites in tau, Ser-262 is the major site for abnormal phosphorylation of tau in AD brain. The kinase known to phosphorylate this particular site is MARK2, whose activation mechanism is yet to be studied. Our first finding that treatment of cells with LiCl, a selective inhibitor of another major tau kinase, glycogen synthase kinase-3␤ (GSK-3␤), inhibits phosphorylation of Ser-262 of tau led us to investigate the possible involvement of GSK-3␤ in MARK2 activation. In vitro kinase reaction revealed that recombinant GSK-3␤ indeed phosphorylates MARK2, whereas it failed to phosphorylate Ser-262 of tau. Our further findings led us to conclude that GSK-3␤ phosphorylates MARK2 on Ser-212, one of the two reported phosphorylation sites (Thr-208 and Ser-212) found in the activation loop of MARK2. Down-regulation of either GSK-3␤ or MARK2 by small interfering RNAs suppressed the level of phosphorylation on Ser-262. These results, respectively, indicated that GSK-3␤ is responsible for phosphorylating Ser-262 of tau through phosphorylation and activation of MARK2 and that the phosphorylation of tau at this particular site is predominantly mediated by a GSK-3␤-MARK2 pathway. These findings are of interest in the context of the pathogenesis of AD.

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confidence: 88%

GSK-3β Directly Phosphorylates and Activates MARK2/PAR-1

Kosuga¹,

Tashiro²,

Kajioka

et al. 2005

Journal of Biological Chemistry

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“…22 In the past, the development of CAA had not been thought to correlate with the presence of common cerebrovascular risk factors, including hypertension, diabetes mellitus, hyperlipidemia, or the severity of atherosclerosis of the cerebral arteries. 23 Thereafter, the correlation between CAA, on the one hand, and cerebral arteriosclerosis and arteriolar sclerosis, on the other, has attracted attention. 6 Recently, the correlation in the severity of SVD and CAA was demonstrated by postmortem pathological investigation of elderly subjects.…”

Section: Relationship Between Caa-ich and Hypertensionmentioning

confidence: 99%

Clinico-Radiological Characteristics and Pathological Diagnosis of Cerebral Amyloid Angiopathy-Related Intracerebral Hemorrhage

Doden

Sato

Sasahara

et al. 2016

Journal of Stroke and Cerebrovascular Diseases

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Objective: We aim to clarify the clinico-radiological characteristics of cerebral amyloid angiopathy-related intracerebral hemorrhage and to investigate the efficacy of pathological diagnosis using biopsy specimens. Method: We retrospectively reviewed 253 consecutive patients with cortico-subcortical hemorrhage who had been admitted to Aizawa Hospital between January 2006 and July 2013. We had performed craniotomy and hematoma evacuation in 48 patients, as well as biopsy of the evacuated hematoma, cerebral parenchyma adjacent to the hematoma, or both, and they were classified according to the histological results (positive or negative for vascular amyloid deposition) and to the Boston criteria. We compared the clinicoradiological characteristics of cerebral amyloid angiopathy-related intracerebral hemorrhage. We also investigated the detection rate of cerebral amyloid angiopathy with respect to the origins of the specimens. Results: Pathological examination revealed that 22 subjects were positive for vascular amyloid. The number of the cerebral microbleeds located in the deep or infratentorial region was significantly larger in the negative group than in the positive group (P < .05). There was no significant difference in the distribution of lobar cerebral microbleeds and in the prevalence of hypertension. In the probable cerebral amyloid angiopathyrelated intracerebral hemorrhage patients, the probability of having vascular amyloid detected by biopsy of both hematoma and parenchyma was 100%. Rebleeding in the postoperative periods was observed in 2 cases (9.1%) of the positive group.Conclusions: Our results demonstrate the importance and safety of biopsy simultaneously performed with hematoma evacuation. Deep or infratentorial microbleeds are less correlated with cerebral amyloid angiopathy-related intracerebral hemorrhage than with noncerebral amyloid angiopathy-related intracerebral hemorrhage.

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“…Brain autopsy studies demonstrated that CAA pathology occurs with a prevalence ranging from 2% at the age of 50 years old to 74% in subjects Ͼ90 years old. [1][2][3][4][5][6][7] Moreover, 92% to 98.5% of patients with Alzheimer disease also have CAA. 1,7 A distinct type of CAA with a genetic basis is called hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D).…”

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confidence: 99%

Descriptive Analysis of the Boston Criteria Applied to a Dutch-Type Cerebral Amyloid Angiopathy Population

Rooden

Grond

Boom

et al. 2009

Stroke

112

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Background and Purpose-Validation of the Boston criteria for the in vivo diagnosis of cerebral amyloid angiopathy (CAA) is challenging, because noninvasive diagnostic tests do not exist. Hereditary cerebral hemorrhage with amyloidosis-Dutch type is an accepted monogenetic model of CAA and diagnosis can be made with certainty based on DNA analysis. The aim of this study was to analyze and refine the existing Boston criteria in patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type. Methods-We performed T2*-weighted MRI in 27 patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type to assess the presence and location of microbleeds, intracranial hemorrhages, and superficial siderosis. Using the Boston criteria, subjects were categorized as having: no hemorrhages, possible CAA, probable CAA, and hemorrhagic lesions not qualifying for CAA. The sensitivity of the Boston criteria was calculated separately using intracranial hemorrhages only and using intracranial hemorrhages and microbleeds. Results-The sensitivity of the Boston criteria for probable CAA increased from 48% to 63% when microbleeds were included. For symptomatic subjects only, the sensitivity was 100%. No hemorrhages were identified in the deep white matter, basal ganglia, thalamus, or brainstem. Superficial siderosis, observed in 6 patients, did not increase the sensitivity of the Boston criteria in our study group. Conclusions-Our data show that using T2*-weighted MRI and including microbleeds increase the sensitivity of the Boston criteria. The exclusion of hemorrhages in the deep white matter, basal ganglia, thalamus, and brainstem does not lower the sensitivity of the Boston criteria.

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Cerebral amyloid angiopathy in the aged

Cited by 177 publications

References 32 publications

GSK-3β Directly Phosphorylates and Activates MARK2/PAR-1

GSK-3β Directly Phosphorylates and Activates MARK2/PAR-1

Clinico-Radiological Characteristics and Pathological Diagnosis of Cerebral Amyloid Angiopathy-Related Intracerebral Hemorrhage

Descriptive Analysis of the Boston Criteria Applied to a Dutch-Type Cerebral Amyloid Angiopathy Population

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