scholarly journals MFG-E8 (LACTADHERIN): a novel marker associated with cerebral amyloid angiopathy

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Paula Marazuela ◽  
Montse Solé ◽  
Anna Bonaterra-Pastra ◽  
Jesús Pizarro ◽  
Jessica Camacho ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Milk Fat ◽  
Serum Levels ◽  
Diagnostic Tools ◽  
Amyloid Angiopathy ◽  
Milk Fat Globule ◽  
Associated Proteins ◽  
Cerebral Amyloid ◽  
Human Brains ◽  
And Control

AbstractBrain accumulation of amyloid-beta (Aβ) is a crucial feature in Alzheimer´s disease (AD) and cerebral amyloid angiopathy (CAA), although the pathophysiological relationship between these diseases remains unclear. Numerous proteins are associated with Aβ deposited in parenchymal plaques and/or cerebral vessels. We hypothesized that the study of these proteins would increase our understanding of the overlap and biological differences between these two pathologies and may yield new diagnostic tools and specific therapeutic targets. We used a laser capture microdissection approach combined with mass spectrometry in the APP23 transgenic mouse model of cerebral-β-amyloidosis to specifically identify vascular Aβ-associated proteins. We focused on one of the main proteins detected in the Aβ-affected cerebrovasculature: MFG-E8 (milk fat globule-EGF factor 8), also known as lactadherin. We first validated the presence of MFG-E8 in mouse and human brains. Immunofluorescence and immunoblotting studies revealed that MFG-E8 brain levels were higher in APP23 mice than in WT mice. Furthermore, MFG-E8 was strongly detected in Aβ-positive vessels in human postmortem CAA brains, whereas MFG-E8 was not present in parenchymal Aβ deposits. Levels of MFG-E8 were additionally analysed in serum and cerebrospinal fluid (CSF) from patients diagnosed with CAA, patients with AD and control subjects. Whereas no differences were found in MFG-E8 serum levels between groups, MFG-E8 concentration was significantly lower in the CSF of CAA patients compared to controls and AD patients. Finally, in human vascular smooth muscle cells MFG-E8 was protective against the toxic effects of the treatment with the Aβ40 peptide containing the Dutch mutation. In summary, our study shows that MFG-E8 is highly associated with CAA pathology and highlights MFG-E8 as a new CSF biomarker that could potentially be used to differentiate cerebrovascular Aβ pathology from parenchymal Aβ deposition.

scholarly journals Circulating AQP4 Levels in Patients with Cerebral Amyloid Angiopathy-Associated Intracerebral Hemorrhage

2021 ◽  
Vol 10 (5) ◽  
pp. 989
Author(s):  
Paula Marazuela ◽  
Anna Bonaterra-Pastra ◽  
Júlia Faura ◽  
Anna Penalba ◽  
Jesús Pizarro ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Functional Outcome ◽  
Cerebral Amyloid Angiopathy ◽  
Serum Levels ◽  
Protective Role ◽  
Outcome Evaluation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Amyloid Angiopathy ◽  
Cerebral Amyloid

Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage (ICH) in elderly patients. Growing evidence suggests a potential role of aquaporin 4 (AQP4) in amyloid-beta-associated diseases, including CAA pathology. Our aim was to investigate the circulating levels of AQP4 in a cohort of patients who had suffered a lobar ICH with a clinical diagnosis of CAA. AQP4 levels were analyzed in the serum of 60 CAA-related ICH patients and 19 non-stroke subjects by enzyme-linked immunosorbent assay (ELISA). The CAA–ICH cohort was divided according to the time point of the functional outcome evaluation: mid-term (12 ± 18.6 months) and long-term (38.5 ± 32.9 months) after the last ICH. Although no differences were found in AQP4 serum levels between cases and controls, lower levels were found in CAA patients presenting specific hemorrhagic features such as ≥2 lobar ICHs and ≥5 lobar microbleeds detected by magnetic resonance imaging (MRI). In addition, CAA-related ICH patients who presented a long-term good functional outcome had higher circulating AQP4 levels than subjects with a poor outcome or controls. Our data suggest that AQP4 could potentially predict a long-term functional outcome and may play a protective role after a lobar ICH.

EVALUATION OF THE UNITED KINGDOM NATIONAL EXTERNAL QUALITY ASSESSMENT SERVICE 2008 (UK NEQAS 2008) GUIDELINES FOR THE DIAGNOSIS OF SUBARACHNOID HEMORRHAGE USING SPECTROPHOTOMETRIC XANTHOCHROMIA: A RETROSPECTIVE STUDY

2009 ◽  
Vol 32 (6S) ◽  
pp. 5
Author(s):  
A Gangloff ◽  
L Nadeau
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Amyloid Angiopathy ◽  
Viral Encephalitis ◽  
Objective Evaluation ◽  
Final Diagnosis ◽  
Amyloid Angiopathy ◽  
The United Kingdom ◽  
Cerebral Amyloid ◽  
The One ◽  
The Uk

Objective: Evaluation of the UK NEQAS 2008 guidelines for the interpretation of spectrophotometric xanthochromia. Method: A search of the laboratory database for all the xanthochromia test results between May 1st 2008 and May 1st 2009 was performed. Medical charts were reviewed for patients of Hôpital de l’Enfant-Jésus (HEJ) that had at least one detectable pigment (bilirubin, oxyhemoglobin, or methemoglobin). Xanthochromia results obtained with 4 different criteria (Chalmers original, Modified Chalmers, Duiser and UK NEQAS 2008) were compared. Results: We reviewed 41 medical charts (2 patients with duplicate lumbar punctures (LP) for a total of 43 LP). For these 41 patients there were 11 positive xanthochromia results, 5 of which were in concordance with a final diagnosis of subarachnoid hemorrhage (SAH). The diagnosis of the 6 other positive xanthochromia results were as follow: meningeal spread of a lymphoma, cerebral amyloid angiopathy, exertional headache, viral encephalitis with a possibility of petechiaes on the cerebral CT and second LP. Interpretation (negative/positive) of 40/43 LP was identical for the 4 methods. 2 LP were positive with Duiser and UK NEQAS 2008 but negative with Chalmers approaches (final diagnosis: SAH and cerebral amyloid angiopathy). 1 LP was positive only by the Duiser method (viral encephalitis). Conclusions: UK NEQAS 2008 guidelines identified all SAH but are sensitive to traumatic and pathologic meningeal lesions. Except for a case of viral encephalitis with a suspicion of cerebral petechiaes on CT, UK NEQAS 2008 gave xanthochromia results similar to the one in use at HEJ (Duiser). Chalmers original and Modified Chalmers methods missed one of the five SAH.

Cerebral Amyloid Angiopathy in Combination with Paroxysmal Atrial Fibrillation

2020 ◽  
Vol 25 (4) ◽  
pp. 31-37
Author(s):  
A. A. Kornilova ◽  
O. V. Lagoda ◽  
M. M. Tanashyan
Keyword(s):  
Atrial Fibrillation ◽  
Cerebral Amyloid Angiopathy ◽  
Paroxysmal Atrial Fibrillation ◽  
Past History ◽  
Laboratory Data ◽  
Clinical Manifestations ◽  
Cerebral Haemorrhage ◽  
Exclusion Criterion ◽  
Amyloid Angiopathy ◽  
Cerebral Amyloid

The present article addresses the definition of cerebral amyloid angiopathy (CAA) and its symptoms based on the analysis of the medical case; the issues of diagnosis and treatment of this pathology are discussed. The Boston criteria, which became the basis for diagnosis, study of clinical manifestations and progression of CAA and approaches to its therapy, are presented. Methods and modes of neuroimaging, including magnetic resonance imaging (MRI), which verify micro cerebral haemorrhage, are described. At the same time, the role and significance of cardiac arrhythmias in the genesis of ischemic stroke are discussed, and scales for assessing the risk of its occurrence are presented. The observation of the neurological, somatic, neuroimaging, neuropsychological status of a 62-year-old patient confirms quite rare combination of probable CAA, paroxysmal atrial fibrillation and repeated hemorrhagic functional apoplexy (FA). The relevance of the case described, is a complex clinical dilemma based on mutually exclusive recommendations for the pharmacological correction of such conditions. It is emphasized that in many multicenter clinical studies on the effectiveness of antithrombotic medication (antiaggregants, anticoagulants) in the treatment and prevention of ischaemic functional apoplexy , an important exclusion criterion is a hemorrhagic stroke in past history (including the multiple changes in haemostasis indicators). Taking into account the obtained clinical and laboratory data in the dynamics, the tactics of treating the described patient were determined. The results of studies related to the treatment of comorbid pathology that should become the subject of the development of a personalized algorithm for managing patients in each specific case, are discussed.

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