Cerebral amyloid angiopathy in the brains of patients with Alzheimer's disease

Ellis, Ronald J.; Olichney, John; Thal, Leon J.; Mirra, Suzanne S.; Morris, John C.; Beekly, Duane; Heyman, Albert

doi:10.1212/wnl.46.6.1592

Cited by 514 publications

(406 citation statements)

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“…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. 5 As mentioned above, the prevalence of CAA in the elderly increases with age.…”

Section: Relationship Between Caa-ich and Hypertensionmentioning

confidence: 99%

“…CAA is commonly found with an incidence of about 80%-100% in AD. [4][5][6] CAA leads to multiple cortico-subcortical or lobar hemorrhages in the elderly, and it is then referred to as CAA-related intracerebral hemorrhage (CAA-ICH). 3,7 Boston criteria were established for CAA-ICH by the Boston Cerebral Amyloid Angiopathy Group, and a definite diagnosis of CAA-ICH can be formulated only by demonstrating lobar or cortico-subcortical hemorrhage and severe CAA with vasculopathy after whole histological investigation of affected brain tissue is obtained at autopsy.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Relationship Between Caa-ich and Hypertensionmentioning

confidence: 99%

Section: Introductionmentioning

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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“…Cerebrovascular abnormalities are common in AD 26, up to 60% of patients having ischaemic WM damage 9, 10, 17, 26 and over 90% having cerebral amyloid angiopathy (CAA) 16, 18, 29. Brain ischaemia is the defining pathological process in vascular dementia but there is evidence that ischaemia has the potential to contribute to the development of AD pathology.…”

Section: Introductionmentioning

confidence: 99%

Pathophysiology of Hypoperfusion of the Precuneus in Early Alzheimer's Disease

2015

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The earliest decline in cerebral perfusion in Alzheimer's disease (AD) is in the medial parietal cortex (precuneus). We have analyzed precuneus in post‐mortem tissue from 70 AD and 37 control brains to explore the pathophysiology of the hypoperfusion: the contribution of arteriolosclerotic small vessel disease (SVD) and cerebral amyloid angiopathy (CAA), and of the vasoconstrictors endothelin‐1 (EDN1) and angiotensin II (Ang II), and the association with Aβ. The myelin‐associated glycoprotein:proteolipid protein‐1 ratio (MAG:PLP1) was used as an indicator of oxygenation of the precuneus prior to death. MAG:PLP1 was reduced ∼50% in early AD (Braak stage III–IV). Although MAG:PLP1 remained low in advanced AD (stage V–VI), the reduction was less pronounced, possibly reflecting falling oxygen demand. Reduction in cortical MAG:PLP1 correlated with elevation in vascular endothelial growth factor (VEGF), another marker of hypoperfusion. Cortical MAG:PLP1 declined nonsignificantly with increasing SVD and CAA, but significantly with the concentration of EDN1, which was elevated approximately 75% in AD. In contrast, with reduction in cortical MAG:PLP1, Ang II level and angiotensin‐converting enzyme (ACE) activity declined, showing a normal physiological response to hypoperfusion. MAG:PLP1 was reduced in the parietal white matter (WM) in AD but here the decline correlated positively (ie, physiologically) with WM EDN1. However, the decline of MAG:PLP1 in the WM was associated with increasing cortical EDN1 and perhaps reflected vasoconstriction of perforating arterioles, which traverse the cortex to perfuse the WM. EDN1 in the cortex correlated highly significantly with both soluble and insoluble Aβ42, shown previously to upregulate neuronal endothelin‐converting enzyme‐2 (ECE2), but not with Aβ40. Our findings demonstrate reduced oxygenation of the precuneus in early AD and suggest that elevated EDN1, resulting from Aβ42‐mediated upregulation of ECE2, is a contributor.

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“…Therefore, occipital CMBs in the M‐CMBs group could have been caused by HV only, or alternatively, by HV with adjunct CAA. Synergistic effects of HV and CAA on the development of lobar CMB has indeed been reported in patients with M‐CMBs in radiological (Cordonnier & van der Flier, 2011; Fazekas et al., 1999; Park et al., 2013) and neuropathological studies (Ellis et al., 1996; Olichney et al., 1995; Thal, Ghebremedhin, Orantges, & Wiestler, 2003). In addition, the presence of multiple lobar CMBs in itself may reflect CAA, even if these are not SL‐CMBs (Benedictus et al., 2013; Mesker et al., 2011).…”

Section: Discussionmentioning

confidence: 99%

Background and distribution of lobar microbleeds in cognitive dysfunction

et al. 2017

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ObjectivesCerebral microbleeds (CMBs) are often observed in memory clinic patients. It has been generally accepted that deep CMBs (D‐CMBs) result from hypertensive vasculopathy (HV), whereas strictly lobar CMBs (SL‐CMBs) result from cerebral amyloid angiopathy (CAA) which frequently coexists with Alzheimer's disease (AD). Mixed CMBs (M‐CMBs) have been partially attributed to HV and also partially attributed to CAA. The aim of this study was to elucidate the differences between SL‐CMBs and M‐CMBs in terms of clinical features and regional distribution.MaterialsWe examined 176 sequential patients in our memory clinic for clinical features and CMB location using susceptibility‐weighted images obtained on a 3T‐MRI. The number of lobar CMBs in SL‐CMBs and M‐CMBs was counted in each cerebral lobe and their regional density was adjusted according to the volume of each lobe.ResultsOf the total 176 patients, 111 patients (63.1%) had CMBs. Within the patients who had CMBs, M‐CMBs were found in 54 patients (48.6%), followed by SL‐CMBs in 35 (31.5%) and D‐CMBs in 19 (17.1%). The SL‐CMB group showed a significantly higher prevalence of family history of dementia, whereas the M‐CMB group showed an increasing trend toward hypertension and smoking. The prevalence of AD was significantly higher in the SL‐CMBs group, whereas the prevalence of AD with cerebrovascular disease was higher in the M‐CMBs group. The regional density of lobar CMBs was significantly higher in the occipital lobe in the M‐CMB group, whereas the SL‐CMB group showed higher regional density between regions an increasing tendency in the parietal and occipital lobe.ConclusionThe between‐group differences in clinical features and regional distribution indicate there to be an etiological relationship of SL‐CMBs to AD and CAA, and M‐CMBs to both HV and CAA.

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Cerebral amyloid angiopathy in the brains of patients with Alzheimer's disease

Cited by 514 publications

References 9 publications

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

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

Pathophysiology of Hypoperfusion of the Precuneus in Early Alzheimer's Disease

Background and distribution of lobar microbleeds in cognitive dysfunction

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