Brain Endothelial Cells Are Exquisite Sensors of Age-Related Circulatory Cues DOI Creative Commons

Michelle B. Chen,

Andrew C. Yang,

Hanadie Yousef

и другие.

Cell Reports, Год журнала: 2020, Номер 30(13), С. 4418 - 4432.e4

Опубликована: Март 1, 2020

Brain endothelial cells (BECs) are key constituents of the blood-brain barrier (BBB), protecting brain from pathogens and restricting access circulatory factors. Yet, because proteins have prominent age-related effects on adult neurogenesis, neuroinflammation, cognitive function in mice, we wondered whether BECs receive potentially relay signals between blood brain. Using single-cell RNA sequencing hippocampal BECs, discover that capillary BECs—compared with arterial venous BECs—undergo greatest transcriptional changes normal aging, upregulating innate immunity oxidative stress response pathways. Short-term infusions aged plasma into young mice recapitulate aspects this aging transcriptome, remarkably, exert rejuvenation transcriptome. Together, these findings suggest age is exquisitely sensitive to cues pinpoint BBB itself as a promising therapeutic target treat disease.

Язык: Английский

Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria DOI

Bruno Dubois,

Howard Feldman, Claudia Jacova

и другие.

The Lancet Neurology, Год журнала: 2014, Номер 13(6), С. 614 - 629

Опубликована: Май 18, 2014

Язык: Английский

Процитировано

3023

Brain Imaging in Alzheimer Disease DOI Open Access

Keith A. Johnson,

Nick C. Fox, Reisa A. Sperling

и другие.

Cold Spring Harbor Perspectives in Medicine, Год журнала: 2012, Номер 2(4), С. a006213 - a006213

Опубликована: Янв. 31, 2012

Imaging has played a variety of roles in the study Alzheimer disease (AD) over past four decades. Initially, computed tomography (CT) and then magnetic resonance imaging (MRI) were used diagnostically to rule out other causes dementia. More recently, modalities including structural functional MRI positron emission (PET) studies cerebral metabolism with fluoro-deoxy-d-glucose (FDG) amyloid tracers such as Pittsburgh Compound-B (PiB) have shown characteristic changes brains patients AD, prodromal even presymptomatic states that can help rule-in AD pathophysiological process. No one modality serve all purposes each unique strengths weaknesses. These their particular utilities are discussed this article. The challenge for future will be combine biomarkers most efficiently facilitate diagnosis, staging, and, importantly, development effective disease-modifying therapies.

Язык: Английский

Процитировано

796

Microglial signatures and their role in health and disease DOI
Oleg Butovsky, Howard L. Weiner

Nature reviews. Neuroscience, Год журнала: 2018, Номер 19(10), С. 622 - 635

Опубликована: Сен. 11, 2018

Язык: Английский

Процитировано

783

Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease DOI
Sahil Khan,

Kalyani Barve,

Maushmi S. Kumar

и другие.

Current Neuropharmacology, Год журнала: 2020, Номер 18(11), С. 1106 - 1125

Опубликована: Май 28, 2020

The only conclusive way to diagnose Alzheimer's is carry out brain autopsy of the patient's tissue and ascertain whether subject had or any other form dementia. However, due non-feasibility such methods, conclude conditions, medical practitioners use tests that examine a mental ability.Accurate diagnosis at an early stage need hour for initiation therapy. cause most cases still remains unknown except where genetic distinctions have been observed. Thus, standard drug regimen ensues in every patient, irrespective cause, which may not always be beneficial halting reversing disease progression. To provide better life patients by suppressing existing symptoms, diagnosis, curative therapy, site-specific delivery drugs, application hyphenated methods like artificial intelligence brought into main field therapeutics.In this review, we compiled hypotheses explain disease, highlighted gene immunotherapy, peptidomimetics, metal chelators, probiotics quantum dots as advancements strategies manage Alzheimer's.Biomarkers, brain-imaging, theranostics, along with intelligence, are understood future management Alzheimer's.

Язык: Английский

Процитировано

544

FDG-PET improves accuracy in distinguishing frontotemporal dementia and Alzheimer's disease DOI Open Access
Norman L. Foster,

Judith L. Heidebrink,

Christopher M. Clark

и другие.

Brain, Год журнала: 2007, Номер 130(10), С. 2616 - 2635

Опубликована: Авг. 19, 2007

Distinguishing Alzheimer's disease (AD) and frontotemporal dementia (FTD) currently relies on a clinical history examination, but positron emission tomography with [(18)F] fluorodeoxyglucose (FDG-PET) shows different patterns of hypometabolism in these disorders that might aid differential diagnosis. Six experts variable FDG-PET experience made independent, forced choice, diagnostic decisions 45 patients pathologically confirmed AD (n = 31) or FTD 14) using five separate methods: (1) review summaries, (2) checklist alone, (3) summary checklist, (4) transaxial scans (5) stereotactic surface projection (SSP) metabolic statistical maps. In addition, we evaluated the effect sequential followed by SSP. Visual interpretation SSP images was superior to assessment had best inter-rater reliability (mean kappa 0.78) accuracy (89.6%). It also highest specificity (97.6%) sensitivity (86%), positive likelihood ratio for (36.5). The addition summaries increased confidence both FTD. particularly helpful when raters were uncertain their after brief training is more reliable accurate distinguishing from than methods alone. adds important information appropriately increases confidence, even among experienced specialists.

Язык: Английский

Процитировано

541

Biochemistry of Amyloid -Protein and Amyloid Deposits in Alzheimer Disease DOI Open Access
Colin L. Masters,

D. J. Selkoe

Cold Spring Harbor Perspectives in Medicine, Год журнала: 2012, Номер 2(6), С. a006262 - a006262

Опубликована: Фев. 21, 2012

Colin L. Masters1 and Dennis J. Selkoe2 The Mental Health Research Institute, University of Melbourne, Parkville 3010, Australia Center for Neurologic Diseases, Harvard Medical School Brigham Women's Hospital, Boston, Massachusetts 02115 Correspondence: c.masters{at}unimelb.edu.au

Язык: Английский

Процитировано

504

Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer's disease DOI
Kaj Blennow,

Bruno Dubois,

Anne M. Fagan

и другие.

Alzheimer s & Dementia, Год журнала: 2014, Номер 11(1), С. 58 - 69

Опубликована: Май 2, 2014

Several potential disease-modifying drugs for Alzheimer's disease (AD) have failed to show any effect on progression in clinical trials, conceivably because the AD subjects are already too advanced derive benefit from treatment and diagnosis based criteria alone introduces a high misdiagnosis rate. Thus, well-validated biomarkers early detection accurate crucial. Low cerebrospinal fluid (CSF) concentrations of amyloid-β (Aβ1-42) peptide, combination with total tau phosphorylated tau, sensitive specific highly predictive dementia patients mild cognitive impairment. However, interlaboratory variations results seen currently available immunoassays concern. Recent worldwide standardization efforts quality control programs include standard operating procedures both preanalytical (e.g., lumbar puncture sample handling) analytical preparation calibration curve) procedures. Efforts also ongoing develop reproducible assays fully automated instruments. These global harmonization measures will provide basis generalized international application CSF trials routine AD.

Язык: Английский

Процитировано

437

Diagnosis of Early Alzheimer’s Disease: Clinical Practice in 2021 DOI Creative Commons
Anton P. Porsteinsson, Richard Isaacson, S. Knox

и другие.

The Journal of Prevention of Alzheimer s Disease, Год журнала: 2021, Номер unknown, С. 1 - 16

Опубликована: Янв. 1, 2021

Alzheimer’s disease is a progressive, irreversible neurodegenerative impacting cognition, function, and behavior. progresses along continuum from preclinical disease, to mild cognitive and/or behavioral impairment then dementia. Recently, clinicians have been encouraged diagnose earlier, before patients progressed The early accurate detection of disease-associated symptoms underlying pathology by fundamental for the screening, diagnosis, subsequent management patients. It also enables their caregivers plan future make appropriate lifestyle changes that could help maintain quality life longer. Unfortunately, detecting early-stage in clinical practice can be challenging hindered several barriers including constraints on clinicians’ time, difficulty accurately diagnosing pathology, healthcare providers often dismiss as part normal aging process. As prevalence this continues grow, current model diagnosis patient will need evolve integrate care across disciplines continuum, beginning with primary care. This review summarizes importance establishing an related practical ‘how-to’ guidance considerations, tools used throughout diagnostic journey.

Язык: Английский

Процитировано

412

HIV-1 transcription and latency: an update DOI Creative Commons
Carine Van Lint,

Sophie Bouchat,

Alessandro Marcello

и другие.

Retrovirology, Год журнала: 2013, Номер 10(1)

Опубликована: Июнь 26, 2013

Combination antiretroviral therapy, despite being potent and life-prolonging, is not curative does eradicate HIV-1 infection since interruption of treatment inevitably results in a rapid rebound viremia. Reactivation latently infected cells harboring transcriptionally silent but replication-competent proviruses potential source persistent residual viremia cART-treated patients. Although multiple reservoirs may exist, the persistence resting CD4+ T carrying latent represents major barrier to eradication. In this review, we will discuss latest reports on molecular mechanisms that regulate latency at transcriptional level, including interference, role cellular factors, chromatin organization epigenetic modifications, viral Tat trans-activator its cofactors. Since also operate post-transcriptional consider inhibition nuclear RNA export translation by microRNAs as barriers gene expression. Finally, review therapeutic approaches clinical studies aimed achieving either sterilizing cure or functional infection, with special emphasis most recent pharmacological strategies reactivate viruses decrease pool reservoirs.

Язык: Английский

Процитировано

316

Towards clinically translatable in vivo nanodiagnostics DOI
Seung Min Park, Amin Aalipour, Ophir Vermesh

и другие.

Nature Reviews Materials, Год журнала: 2017, Номер 2(5)

Опубликована: Май 3, 2017

Язык: Английский

Процитировано

304