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Cerebral amyloid

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https://www.readbyqxmd.com/read/29439352/linking-atrial-fibrillation-with-alzheimer-s-disease-epidemiological-pathological-and-mechanistic-evidence
#1
Masafumi Ihara, Kazuo Washida
Many studies have shown a relationship between atrial fibrillation (AF) and vascular dementia. AF is a major risk factor for stroke, and stroke is the greatest risk factor for vascular dementia. However, the relationship between Alzheimer's disease (AD), the leading cause of dementia, and AF remains unclear. At least four epidemiological studies have reported AF significantly raises the risk of AD 1.5- to 2.5-fold. Chronic cerebral hypoperfusion, resulting from persistent AF, could explain the link as hypoperfusion may mechanistically exacerbate amyloid-β (Aβ) neuropathology, such as senile plaques and amyloid angiopathy, by upregulating Aβ-producing enzymes and lowering Aβ clearance efficiency...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29439351/relationship-of-area-of-soft-drusen-in-retina-with-cerebral-amyloid-%C3%AE-accumulation-and-blood-amyloid-%C3%AE-level-in-the-elderly
#2
Chiho Shoda, Yorihisa Kitagawa, Hiroyuki Shimada, Mitsuko Yuzawa, Amane Tateno, Yoshiro Okubo
BACKGROUND: Histopathological studies have confirmed that soft drusen contains amyloid-β (Aβ). OBJECTIVE: To examine the relationship between the area of soft drusen in the macular area and cerebral Aβ accumulation or plasma Aβ level in elderly persons without dementia. METHODS: Fourteen consecutive patients (18 eyes) aged ≥50 years with macular soft drusen were studied prospectively. From color fundus photographs, the area of soft drusen (pixel) within a 6,000 μm diameter with the macula as center was measured...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29439322/cerebrospinal-fluid-biomarkers-are-differentially-related-to-structural-and-functional-changes-in-dementia-of-the-alzheimer-s-type
#3
Charles B Malpas, Michael M Saling, Dennis Velakoulis, Patricia Desmond, Rodney J Hicks, Henrik Zetterberg, Kaj Blennow, Terence J O'Brien
The two cardinal pathologies of Alzheimer's disease (AD) develop according to distinct anatomical trajectories. Cerebral tau-related pathology first accumulates in the mesial temporal region, while amyloid-related pathology first appears in neocortex. The eventual distributions of these pathologies reflect their anatomical origins. An implication is that the cardinal pathologies might exert preferential effects on the structurofunctional brain changes observed in AD. We investigated this hypothesis in 39 patients with dementia of the Alzheimer's type...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29435980/the-diabetes-drug-liraglutide-reverses-cognitive-impairment-in-mice-and-attenuates-insulin-receptor-and-synaptic-pathology-in-a-non-human-primate-model-of-alzheimer-s-disease
#4
Andre F Batista, Leticia Forny-Germano, Julia R Clarke, Natalia M Lyra E Silva, Jordano Brito-Moreira, Susan E Boehnke, Andrew Winterborn, Brian C Coe, Ann Lablans, Juliana F Vital, Suelen A Marques, Ana M B Martinez, Matthias Gralle, Christian Holscher, William L Klein, Jean-Christophe Houzel, Sergio T Ferreira, Douglas P Munoz, Fernanda G De Felice
Alzheimer's disease (AD) is a devastating neurological disorder that still lacks an effective treatment, and this has stimulated an intense pursuit of disease-modifying therapeutics. Given the increasingly recognized link between AD and defective brain insulin signaling, we investigated the actions of liraglutide, a glucagon-like peptide-1 (GLP-1) analog marketed for treatment of type 2 diabetes, in experimental models of AD. Insulin receptor pathology is an important feature of AD brains that impairs the neuroprotective actions of central insulin signaling...
February 12, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29435558/association-between-amyloid-and-tau-accumulation-in-young-adults-with-autosomal-dominant-alzheimer-disease
#5
Yakeel T Quiroz, Reisa A Sperling, Daniel J Norton, Ana Baena, Joseph F Arboleda-Velasquez, Danielle Cosio, Aaron Schultz, Molly Lapoint, Edmarie Guzman-Velez, John B Miller, Leo A Kim, Kewei Chen, Pierre N Tariot, Francisco Lopera, Eric M Reiman, Keith A Johnson
Importance: It is critically important to improve our ability to diagnose and track Alzheimer disease (AD) as early as possible. Individuals with autosomal dominant forms of AD can provide clues as to which and when biological changes are reliably present prior to the onset of clinical symptoms. Objective: To characterize the associations between amyloid and tau deposits in the brains of cognitively unimpaired and impaired carriers of presenilin 1 (PSEN1) E280A mutation...
February 12, 2018: JAMA Neurology
https://www.readbyqxmd.com/read/29433569/mh84-improves-mitochondrial-dysfunction-in-a-mouse-model-of-early-alzheimer-s-disease
#6
Maximilian Pohland, Maren Pellowska, Heike Asseburg, Stephanie Hagl, Martina Reutzel, Aljoscha Joppe, Dirk Berressem, Schamim H Eckert, Mario Wurglics, Manfred Schubert-Zsilavecz, Gunter P Eckert
BACKGROUND: Current approved drugs for Alzheimer's disease (AD) only attenuate symptoms, but do not cure the disease. The pirinixic acid derivate MH84 has been characterized as a dual gamma-secretase/proliferator activated receptor gamma (PPARγ) modulator in vitro. Pharmacokinetic studies in mice showed that MH84 is bioavailable after oral administration and reaches the brain. We recently demonstrated that MH84 improved mitochondrial dysfunction in a cellular model of AD. In the present study, we extended the pharmacological characterization of MH84 to 3-month-old Thy-1 AβPPSL mice (harboring the Swedish and London mutation in human amyloid precursor protein (APP)) which are characterized by enhanced AβPP processing and cerebral mitochondrial dysfunction, representing a mouse model of early AD...
February 13, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29432519/the-role-of-biomarkers-and-imaging-in-the-clinical-diagnosis-of-dementia
#7
Antony J Bayer
Recognition of dementia relies on a good clinical history, supported by formal cognitive testing, but identifying the subtype of dementia may be wrong in 20% or more of cases. Accuracy may be improved by use of imaging and cerebrospinal fluid (CSF) biomarkers. Structural neuroimaging is recommended for most patients, not just to identify potentially reversible surgical pathology, but also to detect vascular changes and patterns of cerebral atrophy. Functional imaging can help to confirm neurodegeneration and to distinguish dementia subtypes when structural imaging has been inconclusive...
February 8, 2018: Age and Ageing
https://www.readbyqxmd.com/read/29432159/nad-supplementation-normalizes-key-alzheimer-s-features-and-dna-damage-responses-in-a-new-ad-mouse-model-with-introduced-dna-repair-deficiency
#8
Yujun Hou, Sofie Lautrup, Stephanie Cordonnier, Yue Wang, Deborah L Croteau, Eduardo Zavala, Yongqing Zhang, Kanako Moritoh, Jennifer F O'Connell, Beverly A Baptiste, Tinna V Stevnsner, Mark P Mattson, Vilhelm A Bohr
Emerging findings suggest that compromised cellular bioenergetics and DNA repair contribute to the pathogenesis of Alzheimer's disease (AD), but their role in disease-defining pathology is unclear. We developed a DNA repair-deficient 3xTgAD/Polβ+/- mouse that exacerbates major features of human AD including phosphorylated Tau (pTau) pathologies, synaptic dysfunction, neuronal death, and cognitive impairment. Here we report that 3xTgAD/Polβ+/- mice have a reduced cerebral NAD+/NADH ratio indicating impaired cerebral energy metabolism, which is normalized by nicotinamide riboside (NR) treatment...
February 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29429967/primary-central-nervous-system-vasculitis-associated-with-lymphoma
#9
Carlo Salvarani, Robert D Brown, Teresa J H Christianson, John Huston, Stephen M Ansell, Caterina Giannini, Gene G Hunder
OBJECTIVES: To record the clinical findings, response to therapy, and course of patients with primary CNS vasculitis (PCNSV) associated with lymphoma. PATIENTS AND METHODS: We reviewed the histories of 936 patients with a diagnosis of any type of vasculitis and lymphoma who were seen at the Mayo Clinic over a 32-year period. Ten patients with both PCNSV and lymphoma were identified. We compared the findings in these 10 patients with those from 158 patients with PCNSV without lymphoma seen over 29 years...
February 2, 2018: Neurology
https://www.readbyqxmd.com/read/29428576/ganglioside-gm1-protects-against-high-altitude-cerebral-edema-in-rats-by-suppressing-the-oxidative-stress-and-inflammatory-response-via-the-pi3k-akt-nrf2-pathway
#10
Gu Gong, Liang Yin, Libang Yuan, Daming Sui, Yangyang Sun, Haiyu Fu, Liang Chen, Xiaowu Wang
High altitude cerebral edema (HACE) is a severe type of acute mountain sickness (AMS) that occurs in response to a high altitude hypobaric hypoxic (HH) environment. GM1 monosialoganglioside can alleviate brain injury under adverse conditions including amyloid-β-peptide, ischemia and trauma. However, its role in HACE-induced brain damage remains poorly elucidated. In this study, GM1 supplementation dose-dependently attenuated increase in rat brain water content (BWC) induced by hypobaric chamber (7600 m) exposurefor 24 h...
February 8, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29426824/plasma-a%C3%AE-analysis-using-magnetically-labeled-immunoassays-and-pet-18f-florbetapir-binding-in-non-demented-patients-with-major-depressive-disorder
#11
Kuan-Yi Wu, Ing-Tsung Hsiao, Chia-Hsiang Chen, Chia-Yih Liu, Jung-Lung Hsu, Sheng-Yao Huang, Tzu-Chen Yen, Kun-Ju Lin
An increased level of brain amyloid deposition and a decreased level of cerebral spinal fluid (CSF) Aβ42 are currently considered reliable biomarkers of Alzheimer's disease (AD); however, the usefulness of plasma Aβ levels are not well-established. This study investigated the relationships between plasma Aβ levels and cerebral amyloidosis in 36 non-demented patients with major depressive disorder (MDD). All participants underwent 18F-florbetapir PET imaging and provided a blood sample at the same time for immunomagnetic reduction assay to measure the plasma levels of Aβ40 and Aβ42...
February 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29426770/diastereoselective-synthesis-of-fused-cyclopropyl-3-amino-2-4-oxazine-%C3%AE-amyloid-cleaving-enzyme-bace-inhibitors-and-their-biological-evaluation
#12
Jonathan D Low, Michael D Bartberger, Yuan Cheng, Doug Whittington, Quifen Xue, Stephen Wood, Jennifer R Allen, Ana E Minatti
The diastereoselective synthesis and structure activity relationship (SAR) of a series of fused cyclopropyl-3-amino-2,4-oxazine (2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-amine)-containing BACE inhibitors is described. Through these efforts compound 2 was identified as a potent (cell IC50 = 15 nM) BACE inhibitor with acceptable ADME properties. When tested in vivo, compound 2 demonstrated a significant reduction of brain and cerebral spinal fluid (CSF) Aβ40 levels (46% and 66%, respectively) in a rat pharmacodynamic study and thus represents a suitable starting point for the further development of in vivo efficacious compounds for the treatment of Alzheimer's disease...
February 1, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29424326/-risk-of-vitamin-k-antagonists-in-cases-of-cerebral-microbleeds
#13
B J H Verhaar, M W Vernooij, G J Biessels, M Muller
- Cerebral microbleeds are associated with a higher risk of intracerebral hemorrhage.- When microbleeds are detected, the possible underlying pathology should be considered; this includes cerebral amyloid angiopathy and other factors that increase the risk of haemorrhage, particularly hypertension. - No randomised trials have yet been conducted into haemorrhagic complications and cerebral infarctions in patients with microbleeds who take vitamin K antagonists. This means that it is not clear whether the intended prevention of cerebral infarctions outweighs the increased risk of haemorrhage associated with use of vitamin K antagonists by these patients...
2018: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/29424027/relationship-of-type-2-diabetes-to-human-brain-pathology
#14
Jeremy J Pruzin, Peter T Nelson, Erin L Abner, Zoe Arvanitakis
Type 2 diabetes (T2D) and Alzheimer disease (AD) are both highly prevalent diseases worldwide, and each is associated with high-morbidity and high-mortality. Numerous clinical studies have consistently shown that T2D confers a two-fold increased risk for a dementia, including dementia attributable to AD. Yet, the mechanisms underlying this relationship, especially non-vascular mechanisms, remain debated. Cerebral vascular disease (CVD) is likely to be playing a role. But increased AD neuropathologic changes (ADNC), specifically neuritic amyloid plaques (AP) and neurofibrillary tangles (NFT), are also posited mechanisms...
February 8, 2018: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29423148/multiple-lobar-intracerebral-hemorrhage-and-cerebral-amyloid-angiopathy-in-the-setting-of-apoe-%C3%B0-2-a-case-report-of-the-disease-course-and-call-for-improved-treatment-modalities
#15
Patrick Thornley, Stephan Oreskovich, John Provias, Jamie Silva, Kesava Reddy, Aleksa Cenic
We describe a case of multiple cerebral amyloid angiopathy-associated intracerebral hemorrhages (ICH) occurring at multi-focal lobar sites of the brain. A review and discussion of the current literature on the importance of Apolipoprotein E (ApoE) genotyping in prediction of ICH outcome and recurrence follows.
October 2017: Journal of Surgical Case Reports
https://www.readbyqxmd.com/read/29421784/complement-activation-in-capillary-cerebral-amyloid-angiopathy
#16
Ko Matsuo, Akihiro Shindo, Atsushi Niwa, Ken-Ichi Tabei, Hiroyasu Akatsu, Yoshio Hashizume, Haruhiko Akiyama, Takashi Ayaki, Takakuni Maki, Nobukatsu Sawamoto, Ryosuke Takahashi, Shinji Oikawa, Hidekazu Tomimoto
BACKGROUND: Cerebral amyloid angiopathy (CAA) is classified as type 1 with capillary amyloid β (Aβ) or type 2 without capillary Aβ. While it is known that CAA activates complement, an inflammatory mediator, there is no information on the relationship between capillary Aβ and complement activation. METHODS: We evaluated 34 autopsy brains, including 22 with CAA and 12 with other neurodegenerative diseases. We assessed the vascular density of CAA by analyzing the expression of complement (C1q, C3d, C6, C5b-9), macrophage scavenger receptor (MSR), and apolipoprotein E (ApoE)...
February 8, 2018: Dementia and Geriatric Cognitive Disorders
https://www.readbyqxmd.com/read/29420891/design-synthesis-and-evaluation-of-orally-bioavailable-quinoline-indole-derivatives-as-innovative-multitarget-directed-ligands-promotion-of-cell-proliferation-in-the-adult-murine-hippocampus-for-the-treatment-of-alzheimer-s-disease
#17
Zhiren Wang, Jinhui Hu, Xiaoping Yang, Xing Feng, Xingshu Li, Ling Huang, Albert S C Chan
A novel series of quinoline-indole derivatives were synthesized and evaluated as multi-target-directed ligands for the treatment of Alzheimer's disease (AD). Biological evaluation revealed that the derivatives had multifunctional profiles including antioxidant effects, blood-brain barrier (BBB) penetration, biometal chelation, Aβ aggregation modulation and neurotrophic and neuroprotective properties. Moreover, several representative target derivatives demonstrated hippocampal cell proliferation in living adult mice by intracerebroventricular (ICV) injection or oral administration...
February 8, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29414699/propagation-of-an-a%C3%AE-dodecamer-strain-involves-a-three-step-mechanism-and-a-key-intermediate
#18
Dexter N Dean, Pratip Rana, Ryan P Campbell, Preetam Ghosh, Vijayaraghavan Rangachari
Proteinaceous deposits composed of fibrillar amyloid-β (Aβ) are the primary neuropathological hallmarks in Alzheimer disease (AD) brains. The nucleation-dependent aggregation of Aβ is a stochastic process with frequently observed heterogeneity in aggregate size, structure, and conformation that manifests in fibril polymorphism. Emerging evidence indicates that polymorphic variations in Aβ fibrils contribute to phenotypic diversity and the rate of disease progression in AD. We recently demonstrated that a dodecamer strain derived from synthetic Aβ42 propagates to morphologically distinct fibrils and selectively induces cerebral amyloid angiopathy phenotype in transgenic mice...
February 6, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29411449/caide-dementia-risk-score-alzheimer-and-cerebrovascular-pathology-a-population-based-autopsy-study
#19
Babak Hooshmand, Tuomo Polvikoski, Miia Kivipelto, Maarit Tanskanen, Liisa Myllykangas, Mira Mäkelä, Minna Oinas, Anders Paetau, Alina Solomon
BACKGROUND: CAIDE Dementia Risk Score is a tool for estimating dementia risk in the general population. Its longitudinal associations with Alzheimer or vascular neuropathology in the oldest old are not known. AIM: To explore the relationship between CAIDE Dementia Risk Score at baseline and neuritic plaques, neurofibrillary tangles, cerebral infarcts, and cerebral amyloid angiopathy (CAA) after up to 10 years follow-up in the Vantaa 85+ population. METHODS: Study population included 149 participants aged ≥85 years, without dementia at baseline, and with available clinical and autopsy data...
January 25, 2018: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29406924/white-matter-hyperintensities-on-mri-in-dementia-with-lewy-bodies-parkinson-s-disease-with-dementia-and-alzheimer-s-disease
#20
Hideto Joki, Yuichi Higashiyama, Yoshiharu Nakae, Chiharu Kugimoto, Hiroshi Doi, Katsuo Kimura, Hitaru Kishida, Naohisa Ueda, Tatsu Nakano, Tatsuya Takahashi, Shigeru Koyano, Hideyuki Takeuchi, Fumiaki Tanaka
BACKGROUND: In dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD), it is still debated whether white matter hyperintensities (WMH) on MRI reflect atherosclerotic cerebrovascular changes or Alzheimer's disease (AD)-related pathology such as cerebral amyloid angiopathy. To examine AD-related pathology in DLB and PDD, we compared the severity of WMH and medial temporal lobe atrophy among patients with DLB, PDD, non-demented PD (PDND), and AD. METHODS: We retrospectively studied sex- and age-matched outpatients with AD, DLB, PDD, and PDND, as well as subjects without central nervous system disorders as normal controls (n=50 each)...
February 15, 2018: Journal of the Neurological Sciences
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