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Cerebral amyloid

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https://www.readbyqxmd.com/read/28320141/functional-magnetic-resonance-imaging-responses-in-cadasil
#1
Ikreet Cheema, Aaron R Switzer, Cheryl R McCreary, Michael D Hill, Richard Frayne, Bradley G Goodyear, Eric E Smith
OBJECTIVES: The magnitude of the blood oxygen dependent level (BOLD) functional MRI (fMRI) response to visual stimulation is reduced in the small vessel disease cerebral amyloid angiopathy (CAA), reflecting impaired vascular reactivity. We determined whether BOLD responses were reduced in another small vessel disease, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: BOLD fMRI data were collected using a visual stimulus (contrast-reversing checkerboard) and motor task (finger-tapping)...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28318355/dementia-incidence-and-predictors-in-cerebral-amyloid-angiopathy-patients-without-intracerebral-hemorrhage
#2
Li Xiong, Gregoire Boulouis, Andreas Charidimou, Duangnapa Roongpiboonsopit, Michael J Jessel, Marco Pasi, Yael D Reijmer, Panagiotis Fotiadis, Alison Ayres, Emily Merrill, Kristin Schwab, Deborah Blacker, M Edip Gurol, Steven M Greenberg, Anand Viswanathan
Cerebral amyloid angiopathy (CAA) is a common cause of cognitive impairment in older individuals. This study aimed to investigate predictors of dementia in CAA patients without intracerebral hemorrhage (ICH). A total of 158 non-demented patients from the Stroke Service or the Memory Clinic who met the modified Boston Criteria for probable CAA were included. At baseline, neuroimaging markers, including lobar microbleeds (cerebral microbleeds (CMBs)), white matter hyperintensities (WMH), cortical superficial siderosis (cSS), magnetic resonance imaging (MRI)-visible centrum semiovale perivascular spaces (CSO-PVS), lacunes, and medial temporal atrophy (MTA) were assessed...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28304299/low-florbetapir-pet-uptake-and-normal-a%C3%AE-1%C3%A2-%C3%A2-42-cerebrospinal-fluid-in-an-app-ala-713thr-mutation-carrier
#3
Gemma Lombardi, Valentina Berti, Andrea Tedde, Silvia Bagnoli, Irene Piaceri, Cristina Polito, Giulia Lucidi, Camilla Ferrari, Andrea Ginestroni, Marco Moretti, Alberto Pupi, Benedetta Nacmias, Sandro Sorbi
According to the literature, the APP Ala713Thr mutation is associated with Alzheimer's disease and cerebral amyloid angiopathy. We describe a case of dementia clinically compatible with frontotemporal dementia in an APP Ala713Thr mutation carrier in which both [18F]Florbetapir PET uptake and Aβ1-42 cerebrospinal fluid levels were normal. Further evidences are required to establish if this association is only incidental.
March 10, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28303922/correlation-of-cerebral-microbleed-distribution-to-amyloid-burden-in-patients-with-primary-intracerebral-hemorrhage
#4
Hsin-Hsi Tsai, Li-Kai Tsai, Ya-Fang Chen, Sung-Chun Tang, Bo-Ching Lee, Ruoh-Fang Yen, Jiann-Shing Jeng
The underlying pathology of cerebral microbleeds (CMBs) with mixed lobar and deep distribution remains contentious. The aim of this study was to correlate CMBs distribution to β-amyloid burden in patients with primary intracerebral hemorrhage (ICH). Fourty-seven ICH patients underwent magnetic resonance susceptibility-weighted imaging and (11)C-Pittsburgh Compound B positron emission tomography. The amyloid burden was expressed as standardized uptake value ratio with reference to cerebellum, and presented as median (interquartile range)...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28301218/retinal-pathology-is-associated-with-increased-blood-retina-barrier-permeability-in-a-diabetic-and-hypercholesterolaemic-pig-model-beneficial-effects-of-the-lppla2-inhibitor-darapladib
#5
Nimish K Acharya, Xin Qi, Eric L Goldwaser, George A Godsey, Hao Wu, Mary C Kosciuk, Theresa A Freeman, Colin H Macphee, Robert L Wilensky, Venkat Venkataraman, Robert G Nagele
Using a porcine model of diabetes mellitus and hypercholesterolaemia, we previously showed that diabetes mellitus and hypercholesterolaemia is associated with a chronic increase in blood-brain barrier permeability in the cerebral cortex, leading to selective binding of immunoglobulin G and deposition of amyloid-beta1-42 peptide in pyramidal neurons. Treatment with Darapladib (GlaxoSmithKline, SB480848), an inhibitor of lipoprotein-associated phospholipase-A2, alleviated these effects. Here, investigation of the effects of chronic diabetes mellitus and hypercholesterolaemia on the pig retina revealed a corresponding increased permeability of the blood-retina barrier coupled with a leak of plasma components into the retina, alterations in retinal architecture, selective IgG binding to neurons in the ganglion cell layer, thinning of retinal layers due to cell loss and increased glial fibrillary acidic protein expression in Müller cells, all of which were curtailed by treatment with Darapladib...
March 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28299725/defining-the-relationship-between-hypertension-cognitive-decline-and-dementia-a-review
#6
REVIEW
Keenan A Walker, Melinda C Power, Rebecca F Gottesman
Hypertension is a highly prevalent condition which has been established as a risk factor for cardiovascular and cerebrovascular disease. Although the understanding of the relationship between cardiocirculatory dysfunction and brain health has improved significantly over the last several decades, it is still unclear whether hypertension constitutes a potentially treatable risk factor for cognitive decline and dementia. While it is clear that hypertension can affect brain structure and function, recent findings suggest that the associations between blood pressure and brain health are complex and, in many cases, dependent on factors such as age, hypertension chronicity, and antihypertensive medication use...
March 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/28284905/embryonic-mosaic-deletion-of-app-results-in-displaced-reelin-expressing-cells-in-the-cerebral-cortex
#7
D G Callahan, W M Taylor, M Tilearcio, T Cavanaugh, D J Selkoe, T L Young-Pearse
It is widely accepted that amyloid precursor protein (APP) plays a central role in the pathogenesis of Alzheimer's disease. In addition, APP has been proposed to have functions in numerous biological processes including neuronal proliferation, differentiation, migration, axon guidance, and neurite outgrowth, as well as in synapse formation and function. However, germline knockout of APP yields relatively subtle phenotypes, and brain development appears grossly normal. This is thought to be due in part to functional compensation by APP family members and other type I transmembrane proteins...
March 8, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28282808/18f-av-1451-pet-imaging-in-three-patients-with-probable-cerebral-amyloid-angiopathy
#8
Hee Jin Kim, Hanna Cho, David J Werring, Young Kyoung Jang, Yeo Jin Kim, Jin San Lee, Juyoun Lee, Soomin Jun, Seongbeom Park, Young Hoon Ryu, Jae Yong Choi, Young Seok Cho, Seung Hwan Moon, Duk L Na, Chul Hyoung Lyoo, Sang Won Seo
Cerebrovascular deposition of amyloid-β, known as cerebral amyloid angiopathy (CAA), is associated with MRI findings of lobar hemorrhage, cerebral microbleeds, and cortical superficial siderosis. Although pathological studies suggest that tau may co-localize with vascular amyloid, this has not yet been investigated in CAA in vivo. Three patients with probable CAA underwent 11C-Pittsburgh Compound B (PiB) PET or 18F-florbetaben PET to evaluate amyloid burden, and 18F-AV-1451 PET to evaluate paired helical filament tau burden...
March 6, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28282807/radiological-pathological-correlation-in-alzheimer-s-disease-systematic-review-of-antemortem-magnetic-resonance-imaging-findings
#9
Caroline Dallaire-Théroux, Brandy L Callahan, Olivier Potvin, Stephan Saikali, Simon Duchesne
BACKGROUND: The standard method of ascertaining Alzheimer's disease (AD) remains postmortem assessment of amyloid plaques and neurofibrillary degeneration. Vascular pathology, Lewy bodies, TDP-43, and hippocampal sclerosis are frequent comorbidities. There is therefore a need for biomarkers that can assess these etiologies and provide a diagnosis in vivo. OBJECTIVE: We conducted a systematic review of published radiological-pathological correlation studies to determine the relationship between antemortem magnetic resonance imaging (MRI) and neuropathological findings in AD...
March 6, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28275649/population-based-analysis-of-pathological-correlates-of-dementia-in-the-oldest-old
#10
Maarit Tanskanen, Mira Mäkelä, Irma-Leena Notkola, Liisa Myllykangas, Sari Rastas, Minna Oinas, Perttu J Lindsberg, Tuomo Polvikoski, Pentti J Tienari, Anders Paetau
OBJECTIVE: The aim of this study was to analyze brain pathologies which cause dementia in the oldest old population. METHODS: All 601 persons aged ≥85 years living in the city of Vantaa (Finland), on April 1st, 1991 formed the study population of the Vantaa85 +  study, 300 of whom were autopsied during follow-up (79.5% females, mean age-at-death 92 ± 3.7 years). Alzheimer's disease (AD) pathology (tau and beta-amyloid [Aβ]), cerebral amyloid angiopathy (CAA) and Lewy-related pathologies were analyzed...
March 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28269785/the-link-between-type-2-diabetes-and-neurodegeneration-roles-for-amyloid-%C3%AE-amylin-and-tau-proteins
#11
Prashant Bharadwaj, Nadeeja Wijesekara, Milindu Liyanapathirana, Philip Newsholme, Lars Ittner, Paul Fraser, Giuseppe Verdile
A wealth of evidence indicates a strong link between type 2 diabetes (T2D) and neurodegenerative diseases such as Alzheimer's disease (AD). Although the precise mechanism remains unclear, T2D can exacerbate neurodegenerative processes. Brain atrophy, reduced cerebral glucose metabolism, and central nervous system insulin resistance are features of both AD and T2D. The T2D phenotype (glucose dyshomeostasis, insulin resistance, impaired insulin signaling) also promotes AD pathology, namely accumulation of amyloid-β (Aβ) and hyperphosphorylated tau and can induce other aspects of neuronal degeneration including inflammatory and oxidative processes...
March 1, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28269779/alzheimer-s-disease-characterization-of-the-brain-sites-of-the-initial-tau-cytoskeletal-pathology-will-improve-the-success-of-novel-immunological-anti-tau-treatment-approaches
#12
Udo Rüb, Katharina Stratmann, Helmut Heinsen, Kay Seidel, Mohamed Bouzrou, Horst-Werner Korf
Alzheimer's disease (AD) represents the most frequent neurodegenerative disease of the human brain worldwide. Currently practiced treatment strategies for AD only include some less effective symptomatic therapeutic interventions, which unable to counteract the disease course of AD. New therapeutic attempts aimed to prevent, reduce, or remove the extracellular depositions of the amyloid-β protein did not elicit beneficial effects on cognitive deficits or functional decline of AD. In view of the failure of these amyloid-β-based therapeutic trials and the close correlation between the brain pathology of the cytoskeletal tau protein and clinical AD symptoms, therapeutic attention has since shifted to the tau cytoskeletal protein as a novel drug target...
March 2, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28269776/amyloid-related-imaging-abnormalities-in%C3%A2-an-aged-squirrel-monkey-with-cerebral-amyloid-angiopathy
#13
Eric Heuer, Jessica Jacobs, Rebecca Du, Silun Wang, Orion P Keifer, Amarallys F Cintron, Jeromy Dooyema, Yuguang Meng, Xiaodong Zhang, Lary C Walker
Amyloid-related imaging abnormalities (ARIA) in magnetic resonance imaging scans have emerged as indicators of potentially serious side effects in clinical trials of therapeutics for Alzheimer's disease. These anomalies include an edematous type (ARIA-E) that appears as hyperintense (bright) regions by T2-weighted MRI, and a type characterized by the deposition of hemosiderin (ARIA-H) that elicits a hypointense signal, especially in T2* and susceptibility-weighted imaging. ARIA in general has been linked to the presence of amyloid-β (Aβ)-type cerebral amyloid angiopathy, an accumulation of misfolded Aβ protein in the vascular wall that impairs the integrity of brain blood vessels...
March 2, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28269765/central-review-of-amyloid-related-imaging-abnormalities-in-two-phase-iii-clinical-trials-of-bapineuzumab-in-mild-to-moderate-alzheimer-s-disease-patients
#14
Nzeera Ketter, H Robert Brashear, Jennifer Bogert, Jianing Di, Yves Miaux, Achim Gass, Derk D Purcell, Frederik Barkhof, H Michael Arrighi
BACKGROUND: Amyloid-related imaging abnormalities (ARIA) consist of ARIA-E (with effusion or edema) and ARIA-H (hemosiderin deposits [HDs]). OBJECTIVES: To address accurate ascertainment of ARIA identification, a final magnetic resonance imaging (MRI) reading was performed on patients with mild-to-moderate Alzheimer's disease randomized to bapineuzumab IV or placebo during two Phase III trials (APOE ɛ4 allele carriers or noncarriers). METHODS: Final MRI central review consisted of a systematic sequential locked, adjudicated read in 1,331 APOE ɛ4 noncarriers and 1,121 carriers by independent neuroradiologists...
March 2, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28263740/safety-of-disclosing-amyloid-status-in-cognitively-normal-older-adults
#15
Jeffrey M Burns, David K Johnson, Edward P Liebmann, Rebecca J Bothwell, Jill K Morris, Eric D Vidoni
INTRODUCTION: Disclosing amyloid status to cognitively normal individuals remains controversial given our lack of understanding the test's clinical significance and unknown psychological risk. METHODS: We assessed the effect of amyloid status disclosure on anxiety and depression before disclosure, at disclosure, and 6 weeks and 6 months postdisclosure and test-related distress after disclosure. RESULTS: Clinicians disclosed amyloid status to 97 cognitively normal older adults (27 had elevated cerebral amyloid)...
March 3, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28262719/visualization-of-neuritic-plaques-in-alzheimer-s-disease-by-polarization-sensitive-optical-coherence-microscopy
#16
Bernhard Baumann, Adelheid Woehrer, Gerda Ricken, Marco Augustin, Christian Mitter, Michael Pircher, Gabor G Kovacs, Christoph K Hitzenberger
One major hallmark of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) is the deposition of extracellular senile plaques and vessel wall deposits composed of amyloid-beta (Aβ). In AD, degeneration of neurons is preceded by the formation of Aβ plaques, which show different morphological forms. Most of them are birefringent owing to the parallel arrangement of amyloid fibrils. Here, we present polarization sensitive optical coherence microscopy (PS-OCM) for imaging mature neuritic Aβ plaques based on their birefringent properties...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28261150/intranasal-administration-of-the-antisecretory-peptide-af-16-reduces-edema-and-improves-cognitive-function-following-diffuse-traumatic-brain-injury-in-the-rat
#17
Fredrik Clausen, Hans-Arne Hansson, Johan Raud, Niklas Marklund
A synthetic peptide with antisecretory activity, antisecretory factor (AF)-16, improves injury-related deficits in water and ion transport and decreases intracranial pressure after experimental cold lesion injury and encephalitis although its role in traumatic brain injury (TBI) is unknown. AF-16 or an inactive reference peptide was administrated intranasally 30 min following midline fluid percussion injury (mFPI; n = 52), a model of diffuse mild-moderate TBI in rats. Sham-injured (n = 14) or naïve (n = 24) animals were used as controls...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28253913/retinal-vascular-and-structural-changes-are-associated-with-amyloid-burden-in-the-elderly-ophthalmic-biomarkers-of-preclinical-alzheimer-s-disease
#18
S Mojtaba Golzan, Kathryn Goozee, Dana Georgevsky, Alberto Avolio, Pratishtha Chatterjee, Kaikai Shen, Vivek Gupta, Roger Chung, Greg Savage, Carolyn F Orr, Ralph N Martins, Stuart L Graham
BACKGROUND: Retinal imaging may serve as an alternative approach to monitor brain pathology in Alzheimer's disease (AD). In this study, we investigated the association between retinal vascular and structural changes and cerebral amyloid-β (Aβ) plaque load in an elderly cohort. METHODS: We studied a total of 101 participants, including 73 elderly subjects (79 ± 5 years, 22 male) with no clinical diagnosis of AD but reporting some subjective memory change and an additional 28 subjects (70 ± 9 years, 16 male) with clinically established AD...
March 1, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28253546/fdg-metabolism-associated-with-tau-amyloid-interaction-predicts-memory-decline
#19
Bernard J Hanseeuw, Rebecca A Betensky, Aaron P Schultz, Kate V Papp, Elizabeth C Mormino, Jorge Sepulcre, John S Bark, Danielle M Cosio, Molly LaPoint, Jasmeer P Chhatwal, Dorene M Rentz, Reisa A Sperling, Keith Johnson
OBJECTIVE: To evaluate in normal older adults and preclinical Alzheimer's disease (AD) the impact of amyloid and regional tauopathy on cerebral glucose metabolism and subsequent memory decline. METHODS: We acquired positron emission tomography using F18 Flortaucipir (tau), C11 Pittsburgh Compound B (amyloid) and F18 Fluorodeoxyglucose in 90 clinically normal elderly of the Harvard Aging Brain Study. RESULTS: Posterior cingulate metabolism decreased when both amyloid and neocortical tau were high and predicted subsequent memory decline in a larger sample of normal elderly...
March 2, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28246336/apolipoprotein-e-and-alzheimer-disease-the-influence-of-apoe-on-amyloid-%C3%AE-and-other-amyloidogenic-proteins
#20
Tien-Phat V Huynh, Albert A Davis, Jason D Ulrich, David M Holtzman
Alzheimer disease (AD) is one of the fastest-growing causes of death and disability in persons 65 years or older, affecting more than 5 million Americans alone. Clinical manifestations of AD include progressive decline in memory, executive function, language, and other cognitive domains. Research efforts within the last three decades have identified the apolipoprotein E gene (APOE) as the most significant genetic risk factor for late-onset AD, which accounts for >99% of cases. The apoE protein is hypothesized to affect AD pathogenesis through a variety of mechanisms, from its effects on the blood brain barrier, the innate immune system, synaptic function, to the accumulation of amyloid-β (Aβ)...
February 27, 2017: Journal of Lipid Research
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