Journal ArticleDOI
Association of apolipoprotein E epsilon2 and vasculopathy in cerebral amyloid angiopathy.
S.M. Greenberg,J. P. Vonsattel,Alan Z. Segal,R. I. Chiu,Anne E. Clatworthy,Andrew Liao,B. T. Hyman,G. W. Rebeck +7 more
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TLDR
Analysis of a clinical series of patients with CAA-related hemorrhage confirmed an overrepresentation of APOE ϵ2 as well as an association between this allele and earlier age of first hemorrhage, suggesting that APOEϵ2 and ϵ4 might promote CAA’s hemorrhage through separate mechanisms.Abstract:
Objective: Hemorrhage related to cerebral amyloid angiopathy (CAA) appears to occur through a multistep pathway that includes deposition of β-amyloid in cerebral vessels and specific vasculopathic changes in the amyloid-laden vessels, such as cracking of the vessel wall. Recent reports suggest a positive association between CAA-related hemorrhage and both the apolipoprotein E (APOE) ϵ4 allele and, unexpectedly, the APOE ϵ2 allele. Unlike APOE ϵ4, APOE ϵ2 does not appear to act through increased β-amyloid deposition. We therefore sought to determine whether it might specifically accelerate the second step in this pathway, that is, development of the vasculopathic changes that lead to hemorrhage. Methods: To determine the role of APOE in development of vasculopathic changes, we compared APOE genotypes in two groups of postmortem brains: 52 brains with complete amyloid replacement of vessel walls but without vasculopathic changes, and 23 brains with complete amyloid replacement of vessels with the accompanying changes of cracking of the vessel wall and paravascular leaking of blood. Results: Frequency of APOE ϵ2 was significantly greater in the group with vasculopathy (0.09) than the group without (0.01, p = 0.03). The groups did not differ in mean age or extent of neuritic plaques. Analysis of a clinical series of patients with CAA-related hemorrhage confirmed an overrepresentation of APOE ϵ2 as well as an association between this allele and earlier age of first hemorrhage. Conclusions: These data suggest that APOE ϵ2 and ϵ4 might promote CAA-related hemorrhage through separate mechanisms: ϵ4 by enhancing amyloid deposition and ϵ2 by causing amyloid-laden vessels to undergo the vasculopathic changes that lead to rupture.read more
Citations
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Alzheimer’s Disease: The Challenge of the Second Century
TL;DR: Current information suggests that if the disease is detected before the onset of overt symptoms, it is possible that treatments based on knowledge of underlying pathogenesis can and will be effective.
Journal ArticleDOI
Clinical diagnosis of cerebral amyloid angiopathy: Validation of the Boston Criteria
TL;DR: This small pathologic series indicates that the diagnosis of probable CAA can be made during life with high accuracy, and the validity of the Boston diagnostic criteria for cerebral amyloid angiopathy is upheld.
Journal ArticleDOI
Apolipoprotein E in Alzheimer's disease and other neurological disorders
TL;DR: Because convincing evidence ties the APOE genotype to risk of Alzheimer's disease and cerebral amyloid angiopathy, APOE has been studied in other neurological diseases and is associated with poor outcome after traumatic brain injury and brain haemorrhage, although the mechanisms underlying these associations are unclear.
Journal ArticleDOI
Prevalence and risk factors of cerebral microbleeds The Rotterdam Scan Study
Meike W. Vernooij,A. van der Lugt,M. A. Ikram,Piotr A. Wielopolski,Wiro J. Niessen,Albert Hofman,Gabriel P. Krestin,Monique M.B. Breteler +7 more
TL;DR: The data support the hypothesis that strictly lobar microbleeds are related to cerebral amyloid angiopathy, whereas microbleed in a deep or infratentorial location result from hypertensive or atherosclerotic microangiopathy.
Journal ArticleDOI
Alzheimer disease and cerebrovascular pathology: an update.
TL;DR: Small infarcts in AD patients have no essential impact on global cognitive decline which mainly depends on the severity of Alzheimer pathology, but in early stage of AD they may influence and promote the development of dementia.
References
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Journal ArticleDOI
The Consortium to Establish a Registry for Alzheimer's Disease (CERAD): Part II. Standardization of the neuropathologic assessment of Alzheimer's disease
Suzanne S. Mirra,Albert Heyman,Daniel W. McKeel,S. M. Sumi,Barbara J. Crain,L. M. Brownlee,Vogel Fs,James P. Hughes,van Belle G,Leonard Berg +9 more
TL;DR: The Neuropathology Task Force of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed a practical and standardized neuropathology protocol for the postmortem assessment of dementia and control subjects, which provides neuropathologic definitions of such terms as “definite Alzheimer's disease” (AD), “probable AD,” “possible AD” and “normal brain” to indicate levels of diagnostic certainty.
Journal ArticleDOI
Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) Report of the NINDS-SPSP International Workshop*
Irene Litvan,Yves Agid,Donald B. Calne,G. Campbell,Bruno Dubois,Roger C. Duvoisin,Christopher G. Goetz,Lawrence I. Golbe,Jordan Grafman,John H. Growdon,Mark Hallett,Joseph Jankovic,Niall Quinn,Eva Tolosa,David S. Zee +14 more
TL;DR: Criteria that support the diagnosis of progressive supranuclear palsy, and that exclude diseases often confused with PSP, are presented.
Journal ArticleDOI
Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease.
Elizabeth H. Corder,Ann M. Saunders,Neil Risch,Warren J. Strittmatter,Donald E. Schmechel,P. C. Gaskell,J. B. Rimmler,P. A. Locke,Conneally Pm,Kenneth E. Schmader +9 more
TL;DR: A protective effect of the ε2 allele, in addition to the dose effect ofThe ε4 allele in sporadic AD, is demonstrated, which further support the direct involvement of APOE in the pathogenesis of AD.
Journal ArticleDOI
Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease
Donald E. Schmechel,Ann M. Saunders,Warren J. Strittmatter,Barbara J. Crain,Christine M. Hulette,S. H. Joo,Margaret A. Pericak-Vance,Dmitry Goldgaber,A. D. Roses +8 more
TL;DR: In an autopsy series of brains of late-onset AD patients, a strong association of APOE4 allele with increased vascular and plaque A beta deposits is found.
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Beta-amyloid neurotoxicity requires fibril formation and is inhibited by congo red.
Alfredo Lorenzo,Bruce A. Yankner +1 more
TL;DR: The results indicate that beta A neurotoxicity requires fibril formation, and suggest that a common cytopathic effect of amyloid fibrils may contribute to the pathogenesis of Alzheimer disease and other amyloidsoses.