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Cerebral amyloid angiopathy

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https://www.readbyqxmd.com/read/28067897/pathological-changes-in-basement-membranes-and-dermal-connective-tissue-of-skin-from-patients-with-hereditary-cystatin-c-amyloid-angiopathy
#1
Asbjorg Osk Snorradottir, Helgi J Isaksson, Saevar Ingthorsson, Elias Olafsson, Astridur Palsdottir, Birkir Thor Bragason
Hereditary cystatin C amyloid angiopathy (HCCAA) is a genetic disease caused by a mutation in the cystatin C gene. Cystatin C is abundant in cerebrospinal fluid and the most prominent pathology in HCCAA is cerebral amyloid angiopathy due to mutant cystatin C amyloid deposition with associated cerebral hemorrhages, typically in young adult carriers. Analyses of post-mortem brain samples shows that pathological changes are limited to arteries and regions adjacent to arteries. The severity of pathological changes at post-mortem has precluded the elucidation of the evolution of histological changes...
January 9, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28056358/administrations-of-human-adult-ischemia-tolerant-mesenchymal-stem-cells-and-factors-reduce-amyloid-beta-pathology-in-a-mouse-model-of-alzheimer-s-disease
#2
Taoufiq Harach, Fabien Jammes, Charles Muller, Nicolas Duthilleul, Victoria Cheatham, Valentin Zufferey, David Cheatham, Yelizaveta A Lukasheva, Theo Lasser, Tristan Bolmont
The impact of human adult ischemia-tolerant mesenchymal stem cells (hMSCs) and factors (stem cell factors) on cerebral amyloid beta (Aβ) pathology was investigated in a mouse model of Alzheimer's disease (AD). To this end, hMSCs were administered intravenously to APPPS1 transgenic mice that normally develop cerebral Aβ. Quantitative reverse transcriptase polymerase chain reaction biodistribution revealed that intravenously delivered hMSCs were readily detected in APPPS1 brains 1 hour following administration, and dropped to negligible levels after 1 week...
November 24, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28042517/rust-on-the-brain-from-microbleeds-and-its-relevance-to-alzheimer-studies-invited-commentary-on-cacciottolo-neurobiology-of-aging-2016
#3
M Cacciottolo, T E Morgan, C E Finch
Cerebral microbleeds (MB) and small vessel disease (SVD) with congophilic arterial angiopathy (CAA) are increasingly recognized as a variable factor in AD cognitive impairments. This commentary on our recent report on sex-ApoE interactions in MBs published this February, briefly explores three aspects of MBs that could not be fully discussed therein: I, A possible gap between the prevalence of MBs as detected by MRI and post mortem analysis; II, The role of hemoglobin-degradation products in amyloid-attributed neurodegenerative changes; and III, Possible assessment of MB by cerebrospinal fluid (CSF) assays for iron-related markers to better screen patient subgroups for AD interventions...
November 2016: Journal of Alzheimer's Disease and Parkinsonism
https://www.readbyqxmd.com/read/28030895/imaging-of-intracranial-hemorrhage
#4
Jeremy J Heit, Michael Iv, Max Wintermark
Intracranial hemorrhage is common and is caused by diverse pathology, including trauma, hypertension, cerebral amyloid angiopathy, hemorrhagic conversion of ischemic infarction, cerebral aneurysms, cerebral arteriovenous malformations, dural arteriovenous fistula, vasculitis, and venous sinus thrombosis, among other causes. Neuroimaging is essential for the treating physician to identify the cause of hemorrhage and to understand the location and severity of hemorrhage, the risk of impending cerebral injury, and to guide often emergent patient treatment...
December 12, 2016: Journal of Stroke
https://www.readbyqxmd.com/read/28000005/comparison-of-cerebrospinal-fluid-profiles-in-alzheimer-s-disease-with-multiple-cerebral-microbleeds-and-cerebral-amyloid-angiopathy-related-inflammation
#5
Akio Kimura, Masao Takemura, Kuniaki Saito, Nobuaki Yoshikura, Yuichi Hayashi, Naoko Harada, Hiroshi Nishida, Hideto Nakajima, Takashi Inuzuka
Brain magnetic resonance imaging (MRI) of patients with Alzheimer's disease (AD) sometimes reveals multiple cerebral microbleeds (CMBs) and confluent white matter hyperintensities (WMHs) similar to those observed in cerebral amyloid angiopathy-related inflammation (CAA-I). To determine whether there might be common pathophysiological mechanisms underlying the MRI findings of multiple CMBs and confluent WMHs, we investigated the cerebrospinal fluid (CSF) profiles of 38 AD, five amnestic mild cognitive impairment (MCI), and six CAA-I patients...
December 20, 2016: Journal of Neurology
https://www.readbyqxmd.com/read/27989553/cerebrovascular-function-in-presymptomatic-and-symptomatic-individuals-with-hereditary-cerebral-amyloid-angiopathy-a-case-control-study
#6
Anna M van Opstal, Sanneke van Rooden, Thijs van Harten, Eidrees Ghariq, Gerda Labadie, Panagiotis Fotiadis, M Edip Gurol, Gisela M Terwindt, Marieke J H Wermer, Mark A van Buchem, Steven M Greenberg, Jeroen van der Grond
BACKGROUND: Previous work suggests that impairments of cerebrovascular flow or reactivity might be early markers of cerebral amyloid angiopathy (CAA). Hereditary cerebral haemorrhage with amyloidosis-Dutch type (HCHWA-D) is a genetic form of CAA that can be diagnosed before the onset of clinical symptoms by DNA testing. We aimed to investigate whether haemodynamic measures are decreased in presymptomatic and symptomatic HCHWA-D mutation carriers compared with healthy controls. METHODS: In this case-control study, we included presymptomatic and symptomatic HCHWA-D mutation carriers diagnosed through genetic testing and recruited through the HCHWA-D patient association (Katwijk, Netherlands) and the outpatient clinic of the Department of Neurology of the Leiden University Medical Center (Leiden, Netherlands), and healthy controls...
December 15, 2016: Lancet Neurology
https://www.readbyqxmd.com/read/27987381/hypoxia-ischemia-activate-processing-of-amyloid-precursor-protein-impact-of-vascular-dysfunction-in-the-pathogenesis-of-alzheimer-s-disease
#7
REVIEW
Antero Salminen, Anu Kauppinen, Kai Kaarniranta
Alzheimer's disease (AD) is associated with deficiencies in cerebrovascular functions, e.g. reduced cerebral blood flow and capillary amyloid angiopathy, both of which are evident during the early phase of AD, thus local hypoxia/ischemia could augment the pathogenesis of AD. There is abundant literature revealing that exposures to hypoxia/ischemia increase the amyloidogenic processing of amyloid-β precursor protein (APP) leading to the accumulation of amyloid-β peptides in brain. This hypoxia-induced response has been attributed to a significant increase in the activities of β- and γ-secretases, whereas α-secretase activity decreases in hypoxia...
December 17, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27981028/regional-correlations-between-11-c-pib-pet-and-post-mortem-burden-of-amyloid-beta-pathology-in-a-diverse-neuropathological-cohort
#8
Sang Won Seo, Nagehan Ayakta, Lea T Grinberg, Sylvia Villeneuve, Manja Lehmann, Bruce Reed, Charles DeCarli, Bruce L Miller, Howard J Rosen, Adam L Boxer, James P O'Neil, Lee-Way Jin, William W Seeley, William J Jagust, Gil D Rabinovici
Imaging-pathological correlation studies show that in vivo amyloid-β (Aβ) positron emission tomography (PET) strongly predicts the presence of significant Aβ pathology at autopsy. We sought to determine whether regional PiB-PET uptake would improve sensitivity for amyloid detection in comparison with global measures (experiment 1), and to estimate the relative contributions of different Aβ aggregates to in vivo PET signal (experiment 2). In experiment 1, 54 subjects with [(11)C] PiB-PET during life and postmortem neuropathologic examination (85...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/27980116/innate-immunity-stimulation-via-toll-like-receptor-9-ameliorates-vascular-amyloid-pathology-in-tg-swdi-mice-with-associated-cognitive-benefits
#9
Henrieta Scholtzova, Eileen Do, Shleshma Dhakal, Yanjie Sun, Shan Liu, Pankaj D Mehta, Thomas Wisniewski
: Alzheimer's disease (AD) is characterized by the presence of parenchymal amyloid-beta (Aβ) plaques, cerebral amyloid angiopathy (CAA) and neurofibrillary tangles. Currently there are no effective treatments for AD. Immunotherapeutic approaches under development are hampered by complications related to ineffectual clearance of CAA. Genome-wide association studies have demonstrated the importance of microglia in AD pathogenesis. Microglia are the primary innate immune cells of the brain, and depending on their activation state and environment can have beneficial or detrimental effects...
December 15, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27978793/generation-of-alzheimer-s-disease-transgenic-zebrafish-expressing-human-app-mutation-under-control-of-zebrafish-appb-promotor
#10
Yun-Zhu Pu, Liang Liang, Ai-Ling Fu, Yan Liu, Lan Sun, Qian Li, Dan Wu, Man-Ji Sun, Ying-Ge Zhang, Bao-Quan Zhao
Amyloid peptide precursor (APP) as the precursor protein of peptide beta-amyloid (β-amyloid, Aβ), which is thought to play a central role in the pathogenesis of Alzheimer's disease (AD), also has an important effect on the development and progression of AD. Through knocking-in APP gene in animals, numerous transgenic AD models have been set up for the investigation of the mechanisms behind AD pathogenesis and the screening of anti-AD drugs. However, there are some limitations to these models and here is a need for such an AD model that is economic as well as has satisfactory genetic homology with human...
December 1, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27974807/long-term-neprilysin-inhibition-implications-for-arnis
#11
REVIEW
Duncan J Campbell
Neprilysin has a major role in both the generation and degradation of bioactive peptides. LCZ696 (valsartan/sacubitril, Entresto), the first of the new ARNI (dual-acting angiotensin-receptor-neprilysin inhibitor) drug class, contains equimolar amounts of valsartan, an angiotensin-receptor blocker, and sacubitril, a prodrug for the neprilysin inhibitor LBQ657. LCZ696 reduced blood pressure more than valsartan alone in patients with hypertension. In the PARADIGM-HF study, LCZ696 was superior to the angiotensin-converting enzyme inhibitor enalapril for the treatment of heart failure with reduced ejection fraction, and LCZ696 was approved by the FDA for this purpose in 2015...
December 15, 2016: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/27965078/a-high-resolution-analysis-on-the-meteorological-influences-on-spontaneous-intracerebral-hemorrhage-incidence
#12
Marian Christoph Neidert, Michael Sprenger, Marius Mader, Giuseppe Esposito, Jonas Aurel Hosp, Oliver Bozinov, Luca Regli, Jan-Karl Burkhardt
OBJECTIVE: To investigate the influence of meteorological factors on the incidence of intracerebral hemorrhage (ICH). METHODS: We included 295 ICH admissions between 2005 and 2013. The hourly meteorological parameters considered are: surface pressure, temperature, relative humidity, wind gusts and precipitation. To minimize confounding effects of seasonality, data were analyzed using the following three complementary statistical approaches: (i) deviation of daily measure from the 10-year monthly mean at the day of ictus; (ii) deviation from monthly average with respect to changes in daily measures between the day of ictus and two days before; (iii) evolution of daily measures from 5 days before to 5 days after the ICH occurred...
December 10, 2016: World Neurosurgery
https://www.readbyqxmd.com/read/27955679/post-mortem-histopathology-underlying-%C3%AE-amyloid-pet-imaging-following-flutemetamol-f-18-injection
#13
Milos D Ikonomovic, Chris J Buckley, Kerstin Heurling, Paul Sherwin, Paul A Jones, Michelle Zanette, Chester A Mathis, William E Klunk, Aruna Chakrabarty, James Ironside, Azzam Ismail, Colin Smith, Dietmar R Thal, Thomas G Beach, Gill Farrar, Adrian P L Smith
In vivo imaging of fibrillar β-amyloid deposits may assist clinical diagnosis of Alzheimer's disease (AD), aid treatment selection for patients, assist clinical trials of therapeutic drugs through subject selection, and be used as an outcome measure. A recent phase III trial of [(18)F]flutemetamol positron emission tomography (PET) imaging in 106 end-of-life subjects demonstrated the ability to identify fibrillar β-amyloid by comparing in vivo PET to post-mortem histopathology. Post-mortem analyses demonstrated a broad and continuous spectrum of β-amyloid pathology in AD and other dementing and non-dementing disease groups...
December 12, 2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27925301/atypical-case-of-perimesencephalic-subarachnoid-hemorrhage
#14
Konark Malhotra, Shino D Magaki, Maria Inmaculada Cobos Sillero, Harry V Vinters, Reza Jahan, Robert D Brown, David S Liebeskind
Perimesencephalic subarachnoid hemorrhage (PM-SAH) refers to intracranial hemorrhage located in the perimesencephalic cistern. The etiology remains mainly unclear, although venous leakage or rupture has been postulated. We report an interesting case of a 57-year-old healthy man who presented initially with PM-SAH with worsening of subcortical lesions on follow-up neuroimaging. Histopathological examination demonstrated cerebral amyloid angiopathy with perivascular inflammation.
December 7, 2016: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/27915995/lack-of-p-glycoprotein-results-in-impairment-of-removal-of-beta-amyloid-and-increased-intraparenchymal-cerebral-amyloid-angiopathy-after-active-immunization-in-a-transgenic-mouse-model-of-alzheimer-s-disease
#15
Sascha Brückmann, Anja Brenn, Markus Grube, Katharina Niedrig, Silva Holtfreter, Oliver von Bohlen Und Halbach, Martin Groschup, Markus Keller, Silke Vogelgesang
Immunization against beta-amyloid (Aβ) reduces cerebral Aβ deposits and improves cognitive capacities in transgenic mouse models, and thus has been considered a promising disease-modifying therapeutic approach for Alzheimer's disease (AD). Although clinical trials in AD patients have yielded evidence for clearance of parenchymal Aβ plaques, Aβ increases in blood vessels of treated patients. We hypothesize that an age-related decline in the mechanisms that clear Aβ from the brain might be at least in part responsible for the failure to purge and re-distribute Aβ...
December 1, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27915116/7t-mr-of-intracranial-pathology-preliminary-observations-and-comparisons-to-3t-and-1-5t
#16
Emmanuel C Obusez, Mark Lowe, Se-Hong Oh, Irene Wang, Jennifer Bullen, Paul Ruggieri, Virginia Hill, Daniel Lockwood, Todd Emch, Doksu Moon, Gareth Loy, Jonathan Lee, Matthew Kiczek, Manoj Massand, Volodymyr Statsevych, Todd Stultz, Stephen E Jones
PURPOSE: There have been an increasing number of studies involving ultra-high-field 7T of intracranial pathology, however, comprehensive clinical studies of neuropathology at 7T still remain limited. 7T has the advantage of a higher signal-to-noise ratio and a higher contrast-to-noise ratio, compared to current low field clinical MR scanners. We hypothesized 7T applied clinically, may improve detection and characterization of intracranial pathology. MATERIALS AND METHODS: We performed an IRB-approved 7T prospective study of patients with neurological disease who previously had lower field 3T and 1...
November 30, 2016: NeuroImage
https://www.readbyqxmd.com/read/27913939/erratum-to-cerebral-amyloid-angiopathy-in-a-young-man-with-a-history-of-traumatic-brain-injury-a-case-report-and-review-of-the-literature
#17
Yoichi Nakayama, Yohei Mineharu, Yoshiki Arakawa, Sei Nishida, Hirofumi Tsuji, Hidehiko Miyake, Maki Yamaguchi, Sachiko Minamiguchi, Yasushi Takagi, Susumu Miyamoto
No abstract text is available yet for this article.
January 2017: Acta Neurochirurgica
https://www.readbyqxmd.com/read/27913818/-amyloid-positron-emission-tomography-with-18-%C3%A2-f-florbetaben-in-the-diagnostic-workup-of-dementia-patients
#18
S Schönecker, C Prix, T Raiser, N Ackl, E Wlasich, G Stenglein-Krapf, E Mille, M Brendel, O Sabri, M Patt, H Barthel, P Bartenstein, J Levin, A Rominger, A Danek
BACKGROUND: To this day the definite diagnosis of Alzheimer's disease still relies on post-mortem histopathological detection of neurofibrillary tangles and beta-amyloid deposits. Amyloid positron emission tomography (PET) is a new diagnostic tool that enables the in vivo quantification of pathological beta-amyloid deposits. The aim of the current study was to evaluate to what extent (18)F-florbetaben-PET (FBB-PET) influences the diagnosis of patients with dementia. MATERIAL AND METHODS: Imaging with FBB-PET was performed on 33 patients from our outpatient department for cognitive neurology...
December 2, 2016: Der Nervenarzt
https://www.readbyqxmd.com/read/27911290/rare-genetic-variant-in-sorl1-may-increase-penetrance-of-alzheimer-s-disease-in-a-family-with-several-generations-of-apoe-%C3%A9-4-homozygosity
#19
Eva Louwersheimer, Petra E Cohn-Hokke, Yolande A L Pijnenburg, Marjan M Weiss, Erik A Sistermans, Annemieke J Rozemuller, Marc Hulsman, John C van Swieten, Cock M van Duijn, Frederik Barkhof, Teddy Koene, Philip Scheltens, Wiesje M Van der Flier, Henne Holstege
BACKGROUND: The major genetic risk factor for late onset Alzheimer's disease (AD) is the APOE-ɛ4 allele. However, APOE-ɛ4 homozygosity is not fully penetrant, suggesting co-occurrence of additional genetic variants. OBJECTIVE: To identify genetic factors that, next to APOE-ɛ4 homozygosity, contribute to the development of AD. METHODS: We identified a family with nine AD patients spanning four generations, with an inheritance pattern suggestive of autosomal dominant AD, with no variants in PSEN1, PSEN2, or APP...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27905358/-do-cerebral-microbleeds-increase-the-risk-of-hemorrhagic-complications-of-thrombolytic-therapy
#20
T A Polyakova, A V Arablinsky, O S Levin
The role of the cerebral microbleeds (CMB) as a potential predictor of hemorrhagic complications of thrombolytic therapy is discussed. CMB are small perivascular hemosiderin deposits in the brain detected by magnetic resonance imaging in gradient echo T2* or SWI sequences. They are associated (along with leukoaraiosis or lacunes) with cerebral microangiopathies. Most often CMB are associated with hypertensive arteriopathy (the main cause of CMB localization) or cerebral amyloid angiopathy (the main cause of cerebral CMB)...
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
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