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Aberrant expression of miR-148a-3p in Alzheimer's disease and its protective role against amyloid-β induced neurotoxicity.

Neurosci Lett 2021 May 9:135953. Epub 2021 May 9.

Department of Neurology, Shanxian Central Hospital, Heze 274300, Shandong, China. Electronic address:

Objective: The current study investigated the expression change and clinical value of miR-148a-3p in AD patients, and further examined the role of miR-148a-3p in Aβ-induced neurotoxicity in SH-SY5Y cells.

Material And Methods: qRT-PCR was used for the measurement of miR-148a-3p expression levels. ROC curve was established to calculate the diagnostic value of serum miR-148a-3p for AD. Read More

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VEGF counteracts amyloid-β-induced synaptic dysfunction.

Cell Rep 2021 May;35(6):109121

Institut NeuroMyoGène (INMG), Synaptopathies and Autoantibodies, Institut National de la Santé et de la Recherche Médicale (INSERM), U1217, Centre National de la Recherche Scientifique (CNRS) UMR5310, 69000 Lyon, France; Université Claude Bernard Lyon 1, 69000 Lyon, France. Electronic address:

The vascular endothelial growth factor (VEGF) pathway regulates key processes in synapse function, which are disrupted in early stages of Alzheimer's disease (AD) by toxic-soluble amyloid-beta oligomers (Aβo). Here, we show that VEGF accumulates in and around Aβ plaques in postmortem brains of patients with AD and in APP/PS1 mice, an AD mouse model. We uncover specific binding domains involved in direct interaction between Aβo and VEGF and reveal that this interaction jeopardizes VEGFR2 activation in neurons. Read More

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EGFR Aggregation in the Brain.

ACS Chem Neurosci 2021 May 12. Epub 2021 May 12.

Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.

Recent findings showed that preformed fibrils (PFFs) of misfolded proteins, including α-synuclein (α-syn) and amyloid-β (Aβ), activate EGFR in cell cultures and animal models of amyloid propagation. Comparing these supramolecular structures to normal EGFR ligands such as EGF and HB-EGF suggests that these PFFs might trigger the formation of high order clustering of EGFR that stimulates the aggregation of EGFR tyrosine kinase domain (EGFR-TKD) which is known to form fibrils. Subsequently, self-assembled fibril of EGFR-TKDs itself can serve as a seed to induce aggregation of monomeric forms of misfolded proteins in cytoplasm or endosomes. Read More

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Lactoferrin for Mental Health: Neuro-Redox Regulation and Neuroprotective Effects across the Blood-Brain Barrier with Special Reference to Neuro-COVID-19.

J Diet Suppl 2021 May 12:1-35. Epub 2021 May 12.

N-terminus Research Laboratory, Yorba Linda, California, USA.

Overall mental health depends in part on the blood-brain barrier, which regulates nutrient transfer in-and-out of the brain and its central nervous system. Lactoferrin, an innate metal-transport protein, synthesized in the substantia nigra, particularly in dopaminergic neurons and activated microglia is vital for brain physiology. Lactoferrin rapidly crosses the blood-brain barrier receptor-mediated transcytosis and accumulates in the brain capillary endothelial cells. Read More

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Apelin-13 protects human neuroblastoma SH-SY5Y cells against amyloid-beta induced neurotoxicity: Involvement of anti oxidant and anti apoptotic properties.

J Basic Clin Physiol Pharmacol 2021 May 10. Epub 2021 May 10.

Golestan Neuroscience Research Center (GNRC), Department of Anatomy, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.

Objectives: We investigated the effect of apelin-13 on the cellular model of AD, amyloid-β (Aβ) treated SH-SY5Y cells in rats.

Methods: The SH-SY5Y cells were pretreated with different doses of apelin-13 (1, 2.5, 5, and 10 μg/mL), half an hour before adding 50% Aβ treatment. Read More

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Upregulated expression of a subset of genes in ;/ mice: Evidence of an interaction between diabetes-linked obesity and Alzheimer's disease.

FASEB Bioadv 2021 May 2;3(5):323-333. Epub 2021 Mar 2.

Department of Aging Neurobiology Center for Development of Advanced Medicine for Dementia National Center for Geriatrics and Gerontology Obu Aichi Japan.

Clinical studies have indicated that obesity and diabetes are associated with Alzheimer's disease (AD) and neurodegeneration. However, the mechanism by which obesity/diabetes and AD interact with each other and contribute to dementia remains elusive. To obtain insights into their interaction at molecular levels, we performed gene expression analysis of ;/ mice, which were generated by crossing transgenic AD model mice (APP23 mice) with / mice, which are obese and mildly diabetic. Read More

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The contact activation system and vascular factors as alternative targets for Alzheimer's disease therapy.

Res Pract Thromb Haemost 2021 May 3;5(4):e12504. Epub 2021 May 3.

Patricia and John Rosenwald Laboratory of Neurobiology and Genetics The Rockefeller University New York NY USA.

Alzheimer's disease (AD) is the most common neurodegenerative disease, affecting millions of people worldwide. Extracellular beta-amyloid (Aβ) plaques and neurofibrillary tau tangles are classical hallmarks of AD pathology and thus are the prime targets for AD therapeutics. However, approaches to slow or stop AD progression and dementia by reducing Aβ production, neutralizing toxic Aβ aggregates, or inhibiting tau aggregation have been largely unsuccessful in clinical trials. Read More

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Detection of retinal and blood Aβ oligomers with nanobodies.

Alzheimers Dement (Amst) 2021 6;13(1):e12193. Epub 2021 May 6.

School of Medicine Western Sydney University Campbelltown New South Wales Australia.

Introduction: Abnormal retinal changes are increasingly recognized as an early pathological change in Alzheimer's disease (AD). Although amyloid beta oligomers (Aβo) have been shown to accumulate in the blood and retina of AD patients and animals, it is not known whether the early Aβo deposition precedes their accumulation in brain.

Methods And Results: Using nanobodies targeting Aβ and Aβ oligomers we were able to detect Aβ oligomers in the retina and blood but not in the brain of 3-month-old APP/PS1 mice. Read More

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Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer's Disease.

Neuropsychiatr Dis Treat 2021 4;17:1311-1339. Epub 2021 May 4.

Department of Pathophysiology, Medical University of Gdansk, Gdansk, Poland.

Alzheimer's disease (AD) is the most common form of dementia and aging is the most common risk factor for developing the disease. The etiology of AD is not known but AD may be considered as a clinical syndrome with multiple causal pathways contributing to it. The amyloid cascade hypothesis, claiming that excess production or reduced clearance of amyloid-beta (Aβ) and its aggregation into amyloid plaques, was accepted for a long time as the main cause of AD. Read More

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Impact of interval training with probiotic (L. plantarum / Bifidobacterium bifidum) on passive avoidance test, ChAT and BDNF in the hippocampus of rats with Alzheimer's disease.

Neurosci Lett 2021 May 8:135949. Epub 2021 May 8.

Department of Physical Education and Sport Sciences, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran.

It has been suggested that gut microbiota dysbiosis can lead to Alzheimer's disease (AD), inducing the production of many AD-related pre-inflammatory cytokines. On the other hand, daily probiotic administration and regular exercise training are assumed to improve clinical AD-related symptoms. To take this line of research further, this study was aimed at investigating the impact of moderate-intensity interval training (MIIT) with a combined administration of Lactobacillus plantarum and Bifidobacterium bifidum (probiotic, BROB) on the passive avoidance test (Shuttle Box), choline acetyltransferase (ChAT) and the brain derived neurotrophic factor (BDNF) in the hippocampus of a rat model of AD. Read More

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In Vivo Molecular Changes in the Retina of Patients With Multiple Sclerosis.

Invest Ophthalmol Vis Sci 2021 May;62(6):11

Center of Neuroimmunology, Institut d'Investigacions Biomediques August Pi Sunyer, Barcelona, Spain.

Purpose: Raman spectroscopy allows molecular changes to be quantified in vivo from the tissues like the retina. Here we aimed to assess the metabolic changes in the retina of patients with multiple sclerosis (MS).

Methods: We built a Raman spectroscopy prototype by connecting a scanning laser ophthalmoscope to a spectrophotometer. Read More

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Highly Potent and Selective Butyrylcholinesterase Inhibitors for Cognitive Improvement and Neuroprotection.

J Med Chem 2021 May 11. Epub 2021 May 11.

School of Pharmacy, China Pharmaceutical University, Nanjing 211198, People's Republic of China.

Butyrylcholinesterase (BChE) has been considered as a potential therapeutic target for Alzheimer's disease (AD) because of its compensation capacity to hydrolyze acetylcholine (ACh) and its close association with Aβ deposit. Here, we identified (BChE IC = 16 nM) and (BChE IC = 25 nM) as highly effective and selective BChE inhibitors, which were proved to be safe and long-acting. Candidate compounds exhibited neuroprotective effects and the ability to improve cognition in scopolamine- and Aβ peptide-induced cognitive deficit models. Read More

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Hydroxyurea-induced membrane fluidity decreasing as a characterization of neuronal membrane aging in Alzheimer's disease.

Aging (Albany NY) 2021 May 11;13. Epub 2021 May 11.

Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

Aging is one of the significant risk factors for Alzheimer's disease (AD). Therefore, this study aimed to propose a new hypothesis "membrane aging" as a critical pathogenesis of AD. The concept of "membrane aging" was reviewed, and the possible mechanisms of membrane aging as the primary culprit of AD were clarified. Read More

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Heparanase overexpression impedes perivascular clearance of amyloid-β from murine brain: relevance to Alzheimer's disease.

Acta Neuropathol Commun 2021 May 10;9(1):84. Epub 2021 May 10.

Department of Medical Biochemistry and Microbiology, SciLifeLab Uppsala, University of Uppsala, The Biomedical Center Husargatan 3, Box 582, 751 23, Uppsala, Sweden.

Defective amyloid-β (Aβ) clearance from the brain is a major contributing factor to the pathophysiology of Alzheimer's disease (AD). Aβ clearance is mediated by macrophages, enzymatic degradation, perivascular drainage along the vascular basement membrane (VBM) and transcytosis across the blood-brain barrier (BBB). AD pathology is typically associated with cerebral amyloid angiopathy due to perivascular accumulation of Aβ. Read More

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Aβ43 aggregates exhibit enhanced prion-like seeding activity in mice.

Acta Neuropathol Commun 2021 May 10;9(1):83. Epub 2021 May 10.

Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Krembil Discovery Tower, Rm. 4KD481, 60 Leonard Ave., Toronto, ON, M5T 0S8, Canada.

When injected into genetically modified mice, aggregates of the amyloid-β (Aβ) peptide from the brains of Alzheimer's disease (AD) patients or transgenic AD mouse models seed cerebral Aβ deposition in a prion-like fashion. Within the brain, Aβ exists as a pool of distinct C-terminal variants with lengths ranging from 37 to 43 amino acids, yet the relative contribution of individual C-terminal Aβ variants to the seeding behavior of Aβ aggregates remains unknown. Here, we have investigated the relative seeding activities of Aβ aggregates composed exclusively of recombinant Aβ38, Aβ40, Aβ42, or Aβ43. Read More

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Validation of amyloid PET positivity thresholds in centiloids: a multisite PET study approach.

Alzheimers Res Ther 2021 May 10;13(1):99. Epub 2021 May 10.

Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA, USA.

Background: Inconsistent positivity thresholds, image analysis pipelines, and quantitative outcomes are key challenges of multisite studies using more than one β-amyloid (Aβ) radiotracer in positron emission tomography (PET). Variability related to these factors contributes to disagreement and lack of replicability in research and clinical trials. To address these problems and promote Aβ PET harmonization, we used [F]florbetaben (FBB) and [F]florbetapir (FBP) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to derive (1) standardized Centiloid (CL) transformations and (2) internally consistent positivity thresholds based on separate young control samples. Read More

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Towards point-of-care diagnosis of Alzheimer's disease: Multi-analyte based portable chemiresistive platform for simultaneous detection of β-amyloid (1-40) and (1-42) in plasma.

Biosens Bioelectron 2021 May 4;186:113294. Epub 2021 May 4.

Department of Electrical Engineering, Indian Institute of Technology Hyderabad, 502285, India. Electronic address:

Label-free simultaneous detection of Alzheimer's disease (AD) specific biomarkers Aβ40 and Aβ42 peptides on a single platform using polypyrrole nanoparticle-based chemiresistive biosensors is reported here. The proposed interdigitated-microelectrode based inexpensive multisensor-platform can concurrently detect Aβ40 and Aβ42 in spiked-plasma in the range of 10 - 10 g/mL (with LoDs being 5.71 and 9. Read More

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Natural antioxidants enhance the power of physical and mental activities versus risk factors inducing progression of Alzheimer's disease in rats.

Int Immunopharmacol 2021 May 7;96:107729. Epub 2021 May 7.

Pharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt. Electronic address:

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease that is exacerbated by social isolation (SI) and protein malnutrition (PM). Antioxidants, physical and mental activities (Ph&M) can maintain cognitive functions and protect against dementia.

Objective: To investigate the impact of Epigallocatechin-3-gallate (EGCG), Vitamin E (VE), Vitamin C (VC), and Selenium (Se), in enhancing the potential effect of Ph&M versus SI&PM as risk factors in the progression of AD in rats. Read More

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Astrocyte and glutamate involvement in the pathogenesis of epilepsy in Alzheimer's disease.

Epilepsia 2021 May 10. Epub 2021 May 10.

Department of Neuroscience, Central Clinical School, The Alfred Hospital, Monash University, Melbourne, Vic., Australia.

Alzheimer's disease (AD) can increase the risk of epilepsy by up to 10-fold compared to healthy age-matched controls. However, the pathological mechanisms that underlie this increased risk are poorly understood. Because disruption in brain glutamate homeostasis has been implicated in both AD and epilepsy, this might play a mechanistic role in the pathogenesis of epilepsy in AD. Read More

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NMR analysis of the correlation of metabolic changes in blood and cerebrospinal fluid in Alzheimer model male and female mice.

PLoS One 2021 10;16(5):e0250568. Epub 2021 May 10.

National Research Council of Canada, Digital Technologies Research Centre, Ottawa, Canada.

The development of effective therapies as well as early, molecular diagnosis of Alzheimer's disease is impeded by the lack of understanding of the underlying pathological mechanisms. Metabolomics studies of body fluids as well as brain tissues have shown major changes in metabolic profiles of Alzheimer's patients. However, with analysis performed at the late stages of the disease it is not possible to distinguish causes and consequence. Read More

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The Cryo-EM Effect: Structural Biology of Neurodegenerative Disease Aggregates.

J Neuropathol Exp Neurol 2021 May 10. Epub 2021 May 10.

Neurogenerative diseases are characterized by diverse protein aggregates with a variety of microscopic morphologic features. Although ultrastructural studies of human neurodegenerative disease tissues have been conducted since the 1960s, only recently have near-atomic resolution structures of neurodegenerative disease aggregates been described. Solid-state nuclear magnetic resonance spectroscopy and X-ray crystallography have provided near-atomic resolution information about in vitro aggregates but pose logistical challenges to resolving the structure of aggregates derived from human tissues. Read More

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Sex differences in the neuropathological hallmarks of Alzheimer's disease: focus on cognitively intact elderly individuals.

Neuropathol Appl Neurobiol 2021 May 9. Epub 2021 May 9.

Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, P.R. China.

Aims: Women are more vulnerable to Alzheimer's disease (AD) than men. We investigated i) whether and at what age the AD hallmarks, i.e. Read More

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Early changes in visuospatial episodic memory can help distinguish primary age-related tauopathy from Alzheimer's disease.

Neuropathol Appl Neurobiol 2021 May 9. Epub 2021 May 9.

Division of Neuroscience & Experimental Psychology, Faculty of Biology, Medicine and Health, School of Biological Sciences, The University of Manchester, Salford Royal Hospital, Salford, M6 8HD, UK.

The observation of neurofibrillary tangles (NFTs) without associated amyloid-beta (Aβ) in the brains of cognitively normal and cognitively impaired elderly individuals has, for many years, been a source of discussion and controversy. The term "primary age-related tauopathy" (PART) was introduced in 2014 and consensus guidelines for the condition were published [1]. The clinical manifestations of PART have been described (see [2] for review). Read More

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Spastic paraplegia preceding -related familial Alzheimer's disease.

Alzheimers Dement (Amst) 2021 2;13(1):e12186. Epub 2021 May 2.

Neurogenetics Unit 1st Department of Neurology Eginition Hospital School of Medicine National and Kapodistrian University of Athens Athens Greece.

Introduction: We investigated the frequency, neuropathology, and phenotypic characteristics of spastic paraplegia (SP) that precedes dementia in presenilin 1 () related familial Alzheimer's disease (AD).

Methods: We performed whole exome sequencing (WES) in 60 probands with hereditary spastic paraplegia (HSP) phenotype that was negative for variants in known HSP-related genes. Where mutation was identified, brain biopsy was performed. Read More

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Comparing CSF amyloid-beta biomarker ratios for two automated immunoassays, Elecsys and Lumipulse, with amyloid PET status.

Alzheimers Dement (Amst) 2021 1;13(1):e12182. Epub 2021 May 1.

Department of Clinical Chemistry Neurochemistry Laboratory Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam UMC Amsterdam the Netherlands.

Introduction: We evaluated for two novel automated biomarker assays how cerebrospinal fluid (CSF) amyloid beta (Aβ)-ratios improved the concordance with amyloid positron emission tomography (PET) positivity compared to Aβ alone.

Methods: We selected 288 individuals from the Amsterdam Dementia Cohort across the Alzheimer's disease clinical spectrum when they had both CSF and amyloid PET visual read available, regardless of diagnosis. CSF Aβ, phosphorylated tau (p-tau), and total tau (t-tau) were measured with Elecsys and Lumipulse assays, and Aβ with Lumipulse. Read More

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Application of Antibody Fragments Against Aβ With Emphasis on Combined Application With Nanoparticles in Alzheimer's Disease.

Front Pharmacol 2021 22;12:654611. Epub 2021 Apr 22.

Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun, China.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and accumulating evidences suggest a key role of amyloid-β (Aβ) peptide in the pathogenesis of AD. According to the amyloid cascade hypothesis, the imbalance of producing and clearing Aβ is the beginning of neurodegeneration and dementia. Consequently, immunotherapy becomes popular through using antibodies against Aβ. Read More

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Intranasal Delivery of Collagen-Loaded Neprilysin Clears Beta-Amyloid Plaques in a Transgenic Alzheimer Mouse Model.

Christian Humpel

Front Aging Neurosci 2021 22;13:649646. Epub 2021 Apr 22.

Laboratory of Psychiatry and Experimental Alzheimer's Research, Department of Psychiatry and Psychotherapy, Medical University of Innsbruck, Innsbruck, Austria.

Alzheimer's disease (AD) is pathologically characterized by extracellular beta-amyloid (Aβ) plaques and intraneuronal tau tangles in the brain. A therapeutic strategy aims to prevent or clear these Aβ plaques and the Aβ-degrading enzyme neprilysin is a potent drug to degrade plaques. The major challenge is to deliver bioactive neprilysin into the brain via the blood-brain barrier. Read More

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Subcortical and Cortical Regions of Amyloid-β Pathology Measured by 11C-PiB PET Are Differentially Associated with Cognitive Functions and Stages of Disease in Memory Clinic Patients.

J Alzheimers Dis 2021 May 4. Epub 2021 May 4.

Division of Clinical Geriatrics, Department of Neurobiology Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.

Background: The effect of regional brain amyloid-β (Aβ) pathology on specific cognitive functions is incompletely known.

Objective: The relationship between Aβ and cognitive functions was investigated in this cross-sectional multicenter study of memory clinic patients.

Methods: The participants were patients diagnosed with Alzheimer's disease (AD, n = 83), mild cognitive impairment (MCI, n = 60), and healthy controls (HC, n = 32), who had been scanned by 11C-PiB PET in 13 brain regions of both hemispheres and who had been assessed by cognitive tests covering seven domains. Read More

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Insomnia Moderates the Relationship Between Amyloid-β and Cognitive Decline in Late-Life Adults without Dementia.

J Alzheimers Dis 2021 May 5. Epub 2021 May 5.

Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.

Background: It is suggested that not all individuals with elevated Aβ will develop dementia or cognitive impairment. Environment or lifestyle might modulate the association of amyloid pathology with cognition. Insomnia is a risk factor of cognitive disorders including Alzheimer's disease. Read More

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Entorhinal Perfusion Predicts Future Memory Decline, Neurodegeneration, and White Matter Hyperintensity Progression in Older Adults.

J Alzheimers Dis 2021 May 3. Epub 2021 May 3.

Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.

Background: Altered cerebral blood flow (CBF) has been linked to increased risk for Alzheimer's disease (AD). However, whether altered CBF contributes to AD risk by accelerating cognitive decline remains unclear. It also remains unclear whether reductions in CBF accelerate neurodegeneration and development of small vessel cerebrovascular disease. Read More

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