3,234 results match your criteria Cerebral Amyloid Angiopathy


Development of a PET radioligand selective for cerebral amyloid angiopathy.

Nucl Med Biol 2020 May 12. Epub 2020 May 12.

Department of Neurology, VA Pittsburgh HS, Pittsburgh, PA, USA; Department of Psychiatry, VA Pittsburgh HS, Pittsburgh, PA, USA; Department of Geriatric Research Education and Clinical Center, VA Pittsburgh HS, Pittsburgh, PA, USA. Electronic address:

Introduction: Positron emission tomography (PET) using radiolabeled amyloid-binding compounds has advanced the field of Alzheimer's disease (AD) by enabling detection and longitudinal tracking of fibrillar amyloid-β (Aβ) deposits in living people. However, this technique cannot distinguish between Aβ deposits in brain parenchyma (amyloid plaques) from those in blood vessels (cerebral amyloid angiopathy, CAA). Development of a PET radioligand capable of selectively detecting CAA would help clarify its contribution to global brain amyloidosis and clinical symptoms in AD and would help to characterize side-effects of anti-Aβ immunotherapies in AD patients, such as CAA. Read More

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http://dx.doi.org/10.1016/j.nucmedbio.2020.05.001DOI Listing

Impaired amyloid beta clearance and brain microvascular dysfunction are present in the Tg-SwDI mouse model of Alzheimer's disease.

Neuroscience 2020 May 22. Epub 2020 May 22.

Division of Neurotoxicology, National Center for Toxicological Research/US FDA. Electronic address:

Alzheimer's disease (AD) pathology is characterized by amyloid plaques containing amyloid beta (Aβ) peptides, neurofibrillary tangles containing hyperphosphorylated tau protein, and neuronal loss. In addition, Aβ deposition in brain microvessels, known as cerebral amyloid angiopathy (CAA), increases blood-brain barrier (BBB) permeability and induces vascular dysfunction which aggravates AD pathology. The aim of the present study was to characterize neurovascular dysfunction in the Tg-SwDI mouse model of AD. Read More

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http://dx.doi.org/10.1016/j.neuroscience.2020.05.024DOI Listing

Single and simultaneous multiple intracerebral hemorrhages: a radiological review.

Acta Neurol Belg 2020 May 24. Epub 2020 May 24.

Department of Neurology, CHU Nîmes, Hôpital Caremeau, University of Montpellier, 4, Rue Du Pr Debré, 30029, Nîmes Cedex 4, France.

Simultaneous multiple intracerebral hemorrhage (SMICH) is defined as ICH in two or more discrete noncontiguous acute intraparenchymal locations on initial CT. About 5% of ICH patients present with SMICH. ICH/SMICH etiology is classically divided into disorders of primary or secondary origin. Read More

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http://dx.doi.org/10.1007/s13760-020-01385-4DOI Listing

Pick's disease: clinicopathologic characterization of 21 cases.

J Neurol 2020 May 21. Epub 2020 May 21.

Department of Neurology, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA.

Background: Pick's disease (PiD) is a unique subtype of frontotemporal lobar degeneration characterized pathologically by aggregates of 3-Repeat tau. Few studies have examined the clinical variability and disease progression in PiD. We describe the clinical features, neuropsychological profiles and coexistent pathologies in 21 cases of autopsy-confirmed PiD. Read More

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http://dx.doi.org/10.1007/s00415-020-09927-9DOI Listing

The importance of brain banking for dementia practice: the first experience of Turkey.

Cell Tissue Bank 2020 May 20. Epub 2020 May 20.

Division of Neuropathology, Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.

This study reports the results of the first brain tissue banking experience of Turkey in the Unit for Aging Brain and Dementia at Dokuz Eylul University, Department of Geriatric Medicine, Izmir. Here, we have briefly described our efforts on brain banking in our country, which consist of six brains from autopsies that had at least two years of clinical follow-up in the 2015-2017 period. The evaluation led to the diagnosis of two Alzheimer's disease (AD) with cerebral amyloid angiopathy, one AD with dementia with Lewy bodies, one corticobasal degeneration, one multiple system atrophy, one vascular dementia. Read More

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http://dx.doi.org/10.1007/s10561-020-09835-2DOI Listing

Clinical Features and Experimental Models of Cerebral Small Vessel Disease.

Front Aging Neurosci 2020 5;12:109. Epub 2020 May 5.

Department of Neurology, Mie University Graduate School of Medicine, Mie University, Tsu, Japan.

Cerebral small vessel disease (SVD) refers to a group of disease conditions affecting the cerebral small vessels, which include the small arteries, arterioles, capillaries, and postcapillary venules in the brain. SVD is the primary cause of vascular cognitive impairment and gait disturbances in aged people. There are several types of SVD, though arteriolosclerosis, which is mainly associated with hypertension, aging, and diabetes mellitus, and cerebral amyloid angiopathy (CAA) comprise most SVD cases. Read More

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http://dx.doi.org/10.3389/fnagi.2020.00109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214616PMC

Intracranial Hemorrhage Due to Secondary Hypertension from Intracranial Large Vessel Occlusion.

Clin Pract Cases Emerg Med 2020 May 2;4(2):167-170. Epub 2020 Mar 2.

North Florida Regional Medical Center, Department of Vascular and Interventional Neurology, Gainesville, Florida.

Simultaneous hemorrhagic and ischemic strokes have been previously reported in the literature. Typically, these occur in patients secondary to dialysis, cerebral amyloid angiopathy, or thrombotic thrombocytopenic purpura.1,2,3 However, this is the unique case of a 62-year-old Asian female who presented with a hemorrhagic stroke suspected to be secondary to refractory hypertension from intracranial large vessel atherosclerotic flow limiting stenosis, with rapid subsequent large vessel occlusion and ischemic stroke. Read More

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http://dx.doi.org/10.5811/cpcem.2020.1.44908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220007PMC

Cerebral amyloid angiopathy with focal presentation-about 3 cases.

Neuroradiology 2020 May 15. Epub 2020 May 15.

Institut du Vieillissement I-Vie, Hospices Civils de Lyon, 27 rue Gabriel Péri, 69100, Villeurbanne, France.

Cerebral amyloid angiopathy (CAA) is a common cerebrovascular disease involved in ischemic and hemorrhagic strokes, and its progression is correlated to cognitive decline. In vivo diagnosis of CAA is guided by the modified Boston criteria, with the presence of multiple intracerebral hemorrhage or cerebral microbleeds (CMB), or single hemorrhage and cortical superficial siderosis. The diagnosis of CAA is highly dependent on the quality of imaging and the advent of susceptibility-weighted imaging (SWI) sequences has improved sensitivity of MRI to detect hemosiderin deposition and CMB, hallmarks of CAA. Read More

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http://dx.doi.org/10.1007/s00234-020-02450-8DOI Listing

Understanding the Pathophysiology of Cerebral Amyloid Angiopathy.

Int J Mol Sci 2020 May 13;21(10). Epub 2020 May 13.

Cerebrovascular Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy.

Cerebral amyloid angiopathy (CAA), one of the main types of cerebral small vessel disease, is a major cause of spontaneous intracerebral haemorrhage and an important contributor to cognitive decline in elderly patients. Despite the number of experimental in vitro studies and animal models, the pathophysiology of CAA is still largely unknown. Although several pathogenic mechanisms including an unbalance between production and clearance of amyloid beta (Aβ) protein as well as 'the prion hypothesis' have been invoked as possible disease triggers, they do not explain completely the disease pathogenesis. Read More

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http://dx.doi.org/10.3390/ijms21103435DOI Listing

Flexible multidentate benzyldiamine derivatives with high affinity for β-amyloid in cerebral amyloid angiopathy.

Mol Divers 2020 May 14. Epub 2020 May 14.

Department of Radiological Medicine and Oncology, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, People's Republic of China.

Cerebral amyloid angiopathy (CAA) commonly found in the aged is pathologically characterized by β-amyloid (Aβ) deposition in the walls of arteries and capillaries of brain. In this study, four flexible multidentate benzyldiamine derivatives as potential probes for cerebrovascular Aβ deposition were designed and synthesized. In in vitro inhibition assays, the ligands 18-21 displayed high affinities for Aβ aggregates with K values of 1. Read More

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http://dx.doi.org/10.1007/s11030-020-10098-yDOI Listing

Interhemispheric distribution of amyloid and small vessel disease burden in cerebral amyloid angiopathy-related intracerebral hemorrhage.

Eur J Neurol 2020 May 11. Epub 2020 May 11.

Department of Neurology, Toulouse University Hospital, Toulouse, France.

Background And Purpose: Intracerebral hemorrhage (ICH) is a devastating presentation of cerebral amyloid angiopathy (CAA), but the mechanisms leading from vascular amyloid deposition to ICH are not well known. Whether amyloid burden and magnetic resonance imaging (MRI) markers of small vessel disease (SVD) are increased in the ICH-affected hemisphere compared to the ICH-free hemisphere in patients with a symptomatic CAA-related ICH was investigated.

Methods: Eighteen patients with CAA-related ICH and 18 controls with deep ICH who underwent brain MRI and amyloid positron emission tomography using F-florbetapir were prospectively enrolled. Read More

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http://dx.doi.org/10.1111/ene.14301DOI Listing

Correction to: Predictors of localization, outcome, and etiology of spontaneous intracerebral hemorrhages: focus on cerebral amyloid angiopathy.

J Neural Transm (Vienna) 2020 Jun;127(6):973-975

Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Semmelweis u. 6, 6725, Szeged, Hungary.

The original version of this article unfortunately contained a mistake. Read More

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http://dx.doi.org/10.1007/s00702-020-02195-xDOI Listing

Copper stabilizes antiparallel β-sheet fibrils of the amyloid β40 (Aβ40)-Iowa variant.

J Biol Chem 2020 May 6. Epub 2020 May 6.

National Synchrotron Light Source II, Brookhaven National Laboratory, United States.

Cerebral amyloid angiopathy (CAA) is a vascular disorder that primarily involves deposition of the 40-residue-long amyloid β peptide (Aβ40) in and along small blood vessels of the brain. CAA is often associated with Alzheimer's disease (AD), which is characterized by amyloid plaques in the brain parenchyma enriched in the Aβ42 peptide. Several recent studies have suggested a structural origin that underlies the differences between the vascular amyloid deposits in CAA and the parenchymal plaques in AD. Read More

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http://dx.doi.org/10.1074/jbc.RA119.011955DOI Listing

An APP mutation family exhibiting white matter hyperintensities and cortical calcification in East China.

Neurol Sci 2020 Apr 28. Epub 2020 Apr 28.

Department of Neurology, Neuroscience Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, Zhejiang Province, China.

Heterozygous amyloid precursor protein (APP) mutations cause hereditary cerebral amyloid angiopathy (CAA) and autosomal dominant Alzheimer's disease (AD). This study aimed at reporting an APP mutation and its associated clinical and neuroimaging features. The proband and her family members presented with memory loss, psychiatric, and visual symptoms. Read More

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http://dx.doi.org/10.1007/s10072-020-04342-4DOI Listing

Hereditary cerebral amyloid angiopathy, Piedmont-type mutation.

Neurol Genet 2020 Apr 13;6(2):e411. Epub 2020 Mar 13.

MassGeneral Institute for Neurodegenerative Disease (M.G.K., S.J.v.V.), Massachusetts General Hospital and Harvard Medical School, Charlestown; Department of Neurology (M.G.K., S.J.v.V., S.M.G.), Massachusetts General Hospital, Boston; Department of Neurology (M.G.K.), Brigham and Women's Hospital, Boston; J. Philip Kistler Stroke Research Center (S.J.v.V., S.M.G.), Massachusetts General Hospital and Harvard Medical School, Boston; and Neuropathology Service, C. S. Kubik Laboratory for Neuropathology (M.P.F), Massachusetts General Hospital and Harvard Medical School, Boston.

Objective: We present here a case report of a patient with a family history of intracerebral hemorrhages (ICHs) who presented with multiple large lobar hemorrhages in rapid succession, with cognitive sparing, who was found to have a mutation in the β-amyloid coding sequence of amyloid precursor protein (Leu705Val), termed the Piedmont-type mutation, the second ever reported case of this form of hereditary cerebral amyloid angiopathy (CAA).

Methods: Targeted pathologic examination was performed aided by the use of ex vivo MRI.

Results: Severe CAA was observed mainly involving the leptomeningeal vessels and, to a far lesser extent, cortical vessels, with no amyloid plaques or neurofibrillary tangles. Read More

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http://dx.doi.org/10.1212/NXG.0000000000000411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164975PMC

Central nervous system infections produced by varicella zoster virus.

Curr Opin Infect Dis 2020 Jun;33(3):273-278

Department of Neurology.

Purpose Of Review: Varicella zoster virus (VZV) causes varicella, establishes latency, then reactivates to produce herpes zoster. VZV reactivation can also cause central nervous system (CNS) disease with or without rash. Herein, we review these CNS diseases, pathogenesis, diagnosis, and treatment. Read More

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http://dx.doi.org/10.1097/QCO.0000000000000647DOI Listing

A Case of Cerebral Amyloid Angiopathy Presented with Cognitive Decline and Hoarding Behavior.

Psychiatry Investig 2020 Apr 15;17(4):382-384. Epub 2020 Apr 15.

Department of Psychiatry, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea.

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http://dx.doi.org/10.30773/pi.2019.0328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176570PMC
April 2020
1.149 Impact Factor

Association of Cerebral Microbleeds with Cognitive Decline: A Longitudinal Study.

J Alzheimers Dis 2020 ;75(2):571-579

Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

Background: The role of cerebral microbleeds (CMBs) in cognitive impairment remains controversial.

Objective: To investigate the possible links between the presence, progression, number, and location of CMBs and cognition.

Methods: We assessed 792 subjects from the Alzheimer's Disease Neuroimaging Initiative who underwent both brain 3 Tesla MRI scans and cognitive testing. Read More

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http://dx.doi.org/10.3233/JAD-191257DOI Listing
January 2020

Management of Intracerebral Hemorrhage: JACC Focus Seminar.

J Am Coll Cardiol 2020 Apr;75(15):1819-1831

Vanderbilt University School of Medicine, Department of Neurology, Nashville, Tennessee. Electronic address:

Intracerebral hemorrhage (ICH) accounts for a disproportionate amount of stroke-related morbidity and mortality. Although chronic hypertension and cerebral amyloid angiopathy are the underlying cerebral vasculopathies accounting for the majority of ICH, there are a broad range of potential causes, and effective management requires accurate identification and treatment of the underlying mechanism of hemorrhage. Magnetic resonance imaging and vascular imaging techniques play a critical role in identifying disease mechanisms. Read More

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http://dx.doi.org/10.1016/j.jacc.2019.10.066DOI Listing

Cortical superficial siderosis progression in cerebral amyloid angiopathy: Prospective MRI study.

Neurology 2020 Apr 13;94(17):e1853-e1865. Epub 2020 Apr 13.

From the Hemorrhagic Stroke Research Program, J. Philip Kistler Stroke Research Center, Department of Neurology (T.P., P.F., M.P., G.B., L.X., A.D.W., K.M.S., J.R., M.E.G., S.M.G., A.V., A.C.), and Division of Neurocritical Care and Emergency Neurology (J.R.), Massachusetts General Hospital, and MIND Informatics, Massachusetts General Hospital Biomedical Informatics Core (J.R.), Harvard Medical School, Boston; and Department of Pharmacology, Faculty of Medicine (T.P.), Chulalongkorn University, Bangkok, Thailand.

Objective: To investigate the prevalence, predictors, and clinical relevance of cortical superficial siderosis (cSS) progression in cerebral amyloid angiopathy (CAA).

Methods: Consecutive patients with symptomatic CAA meeting Boston criteria in a prospective cohort underwent baseline and follow-up MRI within 1 year. cSS progression was evaluated on an ordinal scale and categorized into mild (score 1-2 = cSS extension within an already present cSS focus or appearance of 1 new cSS focus) and severe progression (score 3-4 = appearance of ≥2 new cSS foci). Read More

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http://dx.doi.org/10.1212/WNL.0000000000009321DOI Listing

Steroid-Responsive Parkinsonism Caused by Cerebral Amyloid Angiopathy-Related Inflammation.

Mov Disord Clin Pract 2020 Apr 13;7(3):329-331. Epub 2020 Feb 13.

Department of Neurology Juntendo University Graduate School of Medicine Tokyo Japan.

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http://dx.doi.org/10.1002/mdc3.12901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111570PMC

The PET Sandwich: Using Serial FDG-PET Scans with Interval Burst Suppression to Assess Ictal Components of Disease.

Neurocrit Care 2020 Apr 6. Epub 2020 Apr 6.

Department of Neurology, Harvard Medical School, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.

Background: Determining the cause of refractory seizures and/or interictal continuum (IIC) findings in the critically ill patient remains a challenge. These electrographic abnormalities may represent primary ictal pathology or may instead be driven by an underlying infectious, inflammatory, or neoplastic pathology that requires targeted therapy. In these cases, it is unclear whether escalating antiepileptic therapy will be helpful or harmful. Read More

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http://dx.doi.org/10.1007/s12028-020-00956-wDOI Listing

Relapsing polychondritis coupling with cerebral amyloid deposit inducing cerebral amyloid angiopathy-related inflammation.

J Thromb Thrombolysis 2020 May;49(4):681-684

Division of Neurology, Department of Medicine, Jichi Medical University, Yakushiji 3311-1, Shimotsuke, Tochigi, 329-0498, Japan.

Cerebral amyloid angiopathy-related inflammation is a syndrome of reversible encephalopathy with cerebral amyloid angiopathy, however the pathology is not well understood. We clear a part of the pathology through the first case of an 80-year-old man with cerebral amyloid angiopathy-related inflammation induced by relapsing polychondritis (RP) analysis. An 80-year-old man was diagnosed with RP by auricular cartilage biopsy. Read More

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http://dx.doi.org/10.1007/s11239-020-02109-4DOI Listing

Non-converter mild cognitive impairment with cerebral amyloid angiopathy may be included among persistent amnestic mild cognitive impairment: a case report.

Psychogeriatrics 2020 Mar 31. Epub 2020 Mar 31.

Department Dementia Prevention and Therapeutics, Graduate School of Medicine, Mie University, Tsu, Japan.

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http://dx.doi.org/10.1111/psyg.12545DOI Listing

Longitudinal Cognitive Decline in a Novel Rodent Model of Cerebral Amyloid Angiopathy Type-1.

Int J Mol Sci 2020 Mar 28;21(7). Epub 2020 Mar 28.

Department of Psychology, Stony Brook University, 100 Nicolls Rd, Stony Brook, NY 11794, USA.

Cerebral amyloid angiopathy (CAA) is a small vessel disease characterized by β-amyloid (Aβ) accumulation in and around the cerebral blood vessels and capillaries and is highly comorbid with Alzheimer's disease (AD). Familial forms of CAA result from mutations within the Aβ domain of the amyloid β precursor protein (AβPP). Numerous transgenic mouse models have been generated around expression of human AβPP mutants and used to study cerebral amyloid pathologies. Read More

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http://dx.doi.org/10.3390/ijms21072348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177469PMC
March 2020
2.862 Impact Factor

Low-Dose Phosphodiesterase III Inhibitor Reduces the Vascular Amyloid Burden in Amyloid-β Protein Precursor Transgenic Mice.

Int J Mol Sci 2020 Mar 26;21(7). Epub 2020 Mar 26.

Division of Neurology, Department of Internal Medicine, Saga University Faculty of Medicine, Saga 849-8501, Japan.

A previous study reported that relatively high-dose cilostazol (0.3%) promoted the drainage of cerebrovascular amyloid-β (Aβ) protein in Aβ Precursor Protein (APP) transgenic mice overexpressing vasculotropic Aβ. We investigated whether lower-dose cilostazol can decrease micro-hemorrhages and Aβ deposition in the brain using APP transgenic mice. Read More

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http://dx.doi.org/10.3390/ijms21072295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177305PMC

Cerebrovascular amyloid Angiopathy in bioengineered vessels is reduced by high-density lipoprotein particles enriched in Apolipoprotein E.

Mol Neurodegener 2020 03 25;15(1):23. Epub 2020 Mar 25.

Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.

Background: Several lines of evidence suggest that high-density lipoprotein (HDL) reduces Alzheimer's disease (AD) risk by decreasing vascular beta-amyloid (Aβ) deposition and inflammation, however, the mechanisms by which HDL improve cerebrovascular functions relevant to AD remain poorly understood.

Methods: Here we use a human bioengineered model of cerebral amyloid angiopathy (CAA) to define several mechanisms by which HDL reduces Aβ deposition within the vasculature and attenuates endothelial inflammation as measured by monocyte binding.

Results: We demonstrate that HDL reduces vascular Aβ accumulation independently of its principal binding protein, scavenger receptor (SR)-BI, in contrast to the SR-BI-dependent mechanism by which HDL prevents Aβ-induced vascular inflammation. Read More

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http://dx.doi.org/10.1186/s13024-020-00366-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093966PMC

Class C CpG Oligodeoxynucleotide Immunomodulatory Response in Aged Squirrel Monkey ().

Front Aging Neurosci 2020 3;12:36. Epub 2020 Mar 3.

Department of Comparative Medicine, The University of Texas MD Anderson Cancer Center, Bastrop, TX, United States.

One means of stimulating the mammalian innate immune system is Toll-like receptor 9 (TLR9) being exposed to unmethylated cytosine-phosphate-guanine (CpG) DNA, also known as pathogen-associated molecular patterns (PAMPs) of microbial origin. Synthetic CpG oligodeoxynucleotides (ODNs) with defined CpG motifs possess broad immunostimulatory properties that make CpG ODNs suitable as therapeutic interventions in a variety of human disease conditions, including Alzheimer's disease (AD). Rodent models are often used to preclinically test the effectiveness of CpG ODN therapeutic agents for AD and other disorders. Read More

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http://dx.doi.org/10.3389/fnagi.2020.00036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063459PMC

Predictors of localization, outcome, and etiology of spontaneous intracerebral hemorrhages: focus on cerebral amyloid angiopathy.

J Neural Transm (Vienna) 2020 Jun 19;127(6):963-972. Epub 2020 Mar 19.

Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Semmelweis u. 6, 6725, Szeged, Hungary.

Despite its clinical relevance, cerebral amyloid angiopathy (CAA) is underdiagnosed worldwide. This retrospective study aimed to assess the incidence, etiology, predictors, and outcome of intracerebral hemorrhages (ICHs) in this region, with special focus on possible underlying CAA. Database screening of acute cares with intracranial hemorrhage diagnosis within 01/07/2014-01/07/2018 were conducted analyzing medical records and imaging. Read More

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http://dx.doi.org/10.1007/s00702-020-02174-2DOI Listing

Cerebral Amyloid Angiopathy: A Clinico-Radiological Study from South India.

Neurol India 2020 Mar-Apr;68(2):378-382

Department of Biostatistics, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.

Introduction: Cerebral amyloid angiopathy (CAA) is a major cause of intracerebral hemorrhage (ICH) and cognitive decline in the elderly. Since it is rarely reported from the developing world, we looked into the clinical profile and neuroimaging associations of CAA.

Materials And Methods: Ours was a retrospective case series of subjects diagnosed with probable/possible CAA between January 2006 and December 2015 as per Boston criteria. Read More

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http://dx.doi.org/10.4103/0028-3886.280646DOI Listing

Clinical features related to CSF level of amyloid Aβ42 and Aβ40 proteins in presence of lobar microbleeds.

Rev Neurol (Paris) 2020 Mar 14. Epub 2020 Mar 14.

Département de Neurologie, Hôpital Lariboisière, Assistance publique-Hôpitaux de Paris, Paris, France; Centre de Neurologie Cognitive, Hôpital Lariboisière, Assistance publique-Hôpitaux de Paris, Paris, France; Université de Paris, Paris, France. Electronic address:

In presence of lobar microbleeds, the exact clinical features related to the level of Aβ42, Aβ40 and to the Aβ40/Aβ42 ratio in the cerebrospinal fluid (CSF) are poorly known. We analyzed in 28 consecutive patients with such lesions, whose clinical or additional magnetic resonance imaging features are related to these biomarkers. The results showed that the presence of absence of hypertension, the extent or the antero-posterior distribution of white matter hyperintensities, the presence or absence of vascular lesions in the deepest parts of the brain, and the presence of dementia are related to variations of Aβ42, Aβ40 or of the Aβ40/Aβ42 ratio in the cerebrospinal fluid. Read More

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http://dx.doi.org/10.1016/j.neurol.2020.02.001DOI Listing

Potential Therapeutic Approaches for Cerebral Amyloid Angiopathy and Alzheimer's Disease.

Int J Mol Sci 2020 Mar 14;21(6). Epub 2020 Mar 14.

Department of Neurology, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka 564-8565, Japan.

Cerebral amyloid angiopathy (CAA) is a cerebrovascular disease directly implicated in Alzheimer's disease (AD) pathogenesis through amyloid-β (Aβ) deposition, which may cause the development and progression of dementia. Despite extensive studies to explore drugs targeting Aβ, clinical benefits have not been reported in large clinical trials in AD patients or presymptomatic individuals at a risk for AD. However, recent studies on CAA and AD have provided novel insights regarding CAA- and AD-related pathogenesis. Read More

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http://dx.doi.org/10.3390/ijms21061992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139812PMC

Potential Role of Venular Amyloid in Alzheimer's Disease Pathogenesis.

Int J Mol Sci 2020 Mar 14;21(6). Epub 2020 Mar 14.

Sunnybrook Research Institute, Biological Sciences, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada.

Insurmountable evidence has demonstrated a strong association between Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA), along with various other cerebrovascular diseases. One form of CAA, which is the accumulation of amyloid-beta peptides (Aβ) along cerebral vessel walls, impairs perivascular drainage pathways and contributes to cerebrovascular dysfunction in AD. To date, CAA research has been primarily focused on arterial Aβ, while the accumulation of Aβ in veins and venules were to a lesser extent. Read More

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http://dx.doi.org/10.3390/ijms21061985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139584PMC

Cognitive deficit, and neuropathological correlates, in the oldest-old.

Rev Neurol (Paris) 2020 Mar 13. Epub 2020 Mar 13.

Département de Neuropathologie Escourolle, AP-HP Sorbonne Université, Paris, France; ICM, équipe Alzheimer-Prions, Paris, France.

Several disorders are usually involved in the cognitive deficit of the oldest old. Alzheimer disease is the commonest. It is usually characterized by progressive memory impairment - neocortical symptoms occurring much later in the course of the disease. Read More

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http://dx.doi.org/10.1016/j.neurol.2020.01.355DOI Listing

Cerebrospinal Fluid Biomarkers in Cerebral Amyloid Angiopathy.

J Alzheimers Dis 2020 ;74(4):1189-1201

Stroke Research Centre, Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, UK.

Background: There is limited data on cerebrospinal fluid (CSF) biomarkers in sporadic amyloid-β (Aβ) cerebral amyloid angiopathy (CAA).

Objective: To determine the profile of biomarkers relevant to neurodegenerative disease in the CSF of patients with CAA.

Methods: We performed a detailed comparison of CSF markers, comparing patients with CAA, Alzheimer's disease (AD), and control (CS) participants, recruited from the Biomarkers and Outcomes in CAA (BOCAA) study, and a Specialist Cognitive Disorders Service. Read More

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http://dx.doi.org/10.3233/JAD-191254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242825PMC
January 2020

Discovering the Italian phenotype of cerebral amyloid angiopathy (CAA): the SENECA project.

Neurol Sci 2020 Mar 12. Epub 2020 Mar 12.

Cerebrovascular Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

Cerebral amyloid angiopathy (CAA) is one of the major types of cerebral small vessel disease, and a leading cause of spontaneous intracerebral hemorrhage and cognitive decline in elderly patients. Although increasingly detected, a number of aspects including the pathophysiology, the clinical and neuroradiological phenotype, and the disease course are still under investigation. The incomplete knowledge of the disease limits the implementation of evidence-based guidelines on patient's clinical management and the development of treatments able to prevent or reduce disease progression. Read More

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http://dx.doi.org/10.1007/s10072-020-04306-8DOI Listing

Prominent amyloid plaque pathology and cerebral amyloid angiopathy in APP V717I (London) carrier - phenotypic variability in autosomal dominant Alzheimer's disease.

Acta Neuropathol Commun 2020 03 12;8(1):31. Epub 2020 Mar 12.

Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, 32610, USA.

The discovery of mutations associated with familial forms of Alzheimer's disease (AD), has brought imperative insights into basic mechanisms of disease pathogenesis and progression and has allowed researchers to create animal models that assist in the elucidation of the molecular pathways and development of therapeutic interventions. Position 717 in the amyloid precursor protein (APP) is a hotspot for mutations associated with autosomal dominant AD (ADAD) and the valine to isoleucine amino acid substitution (V717I) at this position was among the first ADAD mutations identified, spearheading the formulation of the amyloid cascade hypothesis of AD pathogenesis. While this mutation is well described in multiple kindreds and has served as the basis for the generation of widely used animal models of disease, neuropathologic data on patients carrying this mutation are scarce. Read More

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http://dx.doi.org/10.1186/s40478-020-0891-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068954PMC

[Stroke and intracerebral hemorrhage under anticoagulation or platelet inhibition-when should treatment be restarted and how?]

Authors:
Joachim Röther

Internist (Berl) 2020 Apr;61(4):424-430

Kopf- und Neurozentrum, Neurologische Abteilung mit überregionaler Stroke Unit, Neurophysiologie und Neurologischer Intensivmedizin, Asklepios Klinik Altona, Asklepios Campus Hamburg der Semmelweis Universität, Paul-Ehrlich-Straße 1, 22763, Hamburg, Deutschland.

Recurrent stroke is a frequent event and clinical trials that addressed the best secondary prevention are sparse. If patients take a thrombocyte aggregation inhibitor (TAI) before the recurrent stroke, clopidogrel can be chosen instead of aspirin or vice versa but evidence is lacking. A 3-week period of dual antiplatelet treatment might be a good alternative after acute reinfarction. Read More

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http://dx.doi.org/10.1007/s00108-020-00747-7DOI Listing

Endothelial-derived plasma exosome proteins in Alzheimer's disease angiopathy.

FASEB J 2020 Apr 10;34(4):5967-5974. Epub 2020 Mar 10.

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

Small cerebral vascular disease (SCeVD) demonstrated by white matter hyperintensity (WMH) on MRI contributes to the development of dementia in Alzheimer's disease (AD), but it has not been possible to correlate onset, severity, or protein components of SCeVD with characteristics of WMH in living patients. Plasma endothelial-derived exosomes (EDEs) were enriched by two-step immunoabsorption from four groups of participants with no clinical evidence of cerebrovascular disease: cognitively normal (CN) without WMH (CN without SCeVD, n = 20), CN with SCeVD (n = 22), preclinical AD (pAD) + mild cognitive impairment (MCI) without SCeVD (pAD/MCI without SCeVD, n = 22), and pAD/MCI with SCeVD (n = 16) for ELISA quantification of cargo proteins. Exosome marker CD81-normalized EDE levels of the cerebrovascular-selective biomarkers large neutral amino acid transporter 1 (LAT-1), glucose transporter type 1 (Glut-1), and permeability-glycoprotein (p-GP, ABCB1) were similarly significantly higher in the CN with SCeVD and pAD/MCI with SCeVD groups than their corresponding control groups without SCeVD. Read More

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http://dx.doi.org/10.1096/fj.202000034RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233139PMC

Vessel Wall MRI Enhancement in Noninflammatory Cerebral Amyloid Angiopathy.

AJNR Am J Neuroradiol 2020 Mar 5;41(3):446-448. Epub 2020 Mar 5.

Department of Radiological Sciences (K.N.), David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.

Cerebral amyloid angiopathy is characterized by deposition of amyloid-β fibrils in the walls of small-to-medium-sized blood vessels. In this retrospective review of 5 patients with histologically confirmed noninflammatory cerebral amyloid angiopathy, high-resolution vessel wall MRI showed arterial wall enhancement in 2 patients (40%). Despite common consensus of equating vessel wall enhancement with inflammation, this report demonstrates that β-amyloid accumulation alone without inflammation can be associated with arterial wall enhancement in a subset of patients. Read More

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http://dx.doi.org/10.3174/ajnr.A6445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077916PMC

Chronic oral administration of adipoRon reverses cognitive impairments and ameliorates neuropathology in an Alzheimer's disease mouse model.

Mol Psychiatry 2020 Mar 4. Epub 2020 Mar 4.

Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Circulating adiponectin (APN) levels decrease with age and obesity. On the other hand, a reduction in APN levels is associated with neurodegeneration and neuroinflammation. We previously showed that aged adiponectin knockout (APN) mice developed Alzheimer's like pathologies, cerebral insulin resistance, and cognitive impairments. Read More

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http://dx.doi.org/10.1038/s41380-020-0701-0DOI Listing

The Alzheimer's Disease Amyloid-Beta Hypothesis in Cardiovascular Aging and Disease: JACC Focus Seminar.

J Am Coll Cardiol 2020 Mar;75(8):952-967

Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Department of Cardiology, Freeman Hospital, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom; NIHR Newcastle Biomedical Research Centre, Newcastle University and Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, United Kingdom. Electronic address:

Aging-related cellular and molecular processes including low-grade inflammation are major players in the pathogenesis of cardiovascular disease (CVD) and Alzheimer's disease (AD). Epidemiological studies report an independent interaction between the development of dementia and the incidence of CVD in several populations, suggesting the presence of overlapping molecular mechanisms. Accumulating experimental and clinical evidence suggests that amyloid-beta (Aβ) peptides may function as a link among aging, CVD, and AD. Read More

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http://dx.doi.org/10.1016/j.jacc.2019.12.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042886PMC

Analyses of Mortality and Prevalence of Cerebrovascular Disease in Colombia, South America (2014-2016): A Cross-Sectional and Ecological Study.

J Stroke Cerebrovasc Dis 2020 May 29;29(5):104699. Epub 2020 Feb 29.

Master of Science in Epidemiology Program, Universidad El Bosque, Bogota D.C, Colombia.

Background: Stroke is the second cause of death and the first cause of disability worldwide. However, although numerous reports regarding stroke epidemiology in Latin America have been published, they differ widely in terms of employed methods and end points. This is the first of a series of articles that describes the epidemiology of stroke and other cerebrovascular diseases (CVD) in the nation, as well as their correlation with recognized risk factors and social variables. Read More

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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104699DOI Listing

Robust neuroinflammation and perivascular pathology in rTg-DI rats, a novel model of microvascular cerebral amyloid angiopathy.

J Neuroinflammation 2020 Mar 4;17(1):78. Epub 2020 Mar 4.

Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, George & Anne Ryan Institute for Neuroscience, University of Rhode Island, 130 Flagg Road, Kingston, RI, 02881, USA.

Background: Cerebral amyloid angiopathy (CAA) is a common cerebral small vessel disease of the aged and a prominent comorbidity of Alzheimer's disease (AD). CAA can promote a variety of vascular-related pathologies including neuroinflammation, cerebral infarction, and hemorrhages, which can all contribute to vascular cognitive impairment and dementia (VCID). Our understanding of the pathogenesis of CAA remains limited and further investigation of this condition requires better preclinical animal models that more accurately reflect the human disease. Read More

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http://dx.doi.org/10.1186/s12974-020-01755-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055091PMC
March 2020
5.408 Impact Factor

Copathology in Progressive Supranuclear Palsy: Does It Matter?

Mov Disord 2020 Mar 3. Epub 2020 Mar 3.

German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.

Background: The influence of concomitant brain pathologies on the progression rate in PSP is unclear.

Objectives: To analyze the frequency and severity of copathologies and their impact on the progression in PSP.

Methods: We analyzed clinic-pathological features of 101 PSP patients. Read More

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http://dx.doi.org/10.1002/mds.28011DOI Listing

Characterization and preclinical evaluation of the cGMP grade DNA based vaccine, AV-1959D to enter the first-in-human clinical trials.

Neurobiol Dis 2020 Jun 28;139:104823. Epub 2020 Feb 28.

Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA. Electronic address:

The DNA vaccine, AV-1959D, targeting N-terminal epitope of Aβ peptide, has been proven immunogenic in mice, rabbits, and non-human primates, while its therapeutic efficacy has been shown in mouse models of Alzheimer's disease (AD). Here we report for the first time on IND-enabling biodistribution and safety/toxicology studies of cGMP-grade AV-1959D vaccine in the Tg2576 mouse model of AD. We also tested acute neuropathology safety profiles of AV-1959D in another AD disease model, Tg-SwDI mice with established vascular and parenchymal Aβ pathology in a pre-clinical translational study. Read More

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http://dx.doi.org/10.1016/j.nbd.2020.104823DOI Listing
June 2020
5.078 Impact Factor

Editorial: Cerebral Small Vessel Diseases: From Vessel Alterations to Cortical Parenchymal Injury.

Front Neurol 2020 14;11:92. Epub 2020 Feb 14.

Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.

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http://dx.doi.org/10.3389/fneur.2020.00092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033488PMC
February 2020

Migraine With Aura as Early Disease Marker in Hereditary Dutch-Type Cerebral Amyloid Angiopathy.

Stroke 2020 Apr 2;51(4):1094-1099. Epub 2020 Mar 2.

From the Department of Neurology (E.A.K., S.V., I.R., E.S.v.E., M.J.H.W., G.M.T.), Leiden University Medical Center, the Netherlands.

Background and Purpose- To determine whether migraine, which has often been described as an inaugural manifestation in monogenic cerebrovascular syndromes, is associated with cerebral amyloid pathology, we assessed migraine and its correlation with magnetic resonance imaging markers in Hereditary Dutch-Type Cerebral Amyloid Angiopathy (D-CAA or Hereditary Cerebral Hemorrhage With Amyloidosis-Dutch type). Methods- All D-CAA mutation carriers who visited our clinic between 2012 and 2018 were included. Migraine was diagnosed by an interview and classified according to the . Read More

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http://dx.doi.org/10.1161/STROKEAHA.119.028170DOI Listing

Amylin and pramlintide modulate γ-secretase level and APP processing in lipid rafts.

Sci Rep 2020 Feb 28;10(1):3751. Epub 2020 Feb 28.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, USA.

A major characteristic of Alzheimer's disease (AD) is the accumulation of misfolded amyloid-β (Aβ) peptide. Several studies linked AD with type 2 diabetes due to similarities between Aβ and human amylin. This study investigates the effect of amylin and pramlintide on Aβ pathogenesis and the predisposing molecular mechanism(s) behind the observed effects in TgSwDI mouse, a cerebral amyloid angiopathy (CAA) and AD model. Read More

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http://dx.doi.org/10.1038/s41598-020-60664-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048857PMC
February 2020