Endoscopic Spine Surgery Past, Present, and Future.
Bull Hosp Jt Dis (2013). 2019 Mar;77(1):75-84
Authors: Hasan S, Hofstetter CP
Abstract
PMID: 30865869 [PubMed - indexed for MEDLINE]
Pancreatic Adenocarcinoma, Version 1.2019.
J Natl Compr Canc Netw. 2019 03 01;17(3):202-210
Authors: Tempero MA, Malafa MP, Chiorean EG, Czito B, Scaife C, Narang AK, Fountzilas C, Wolpin BM, Al-Hawary M, Asbun H, Behrman SW, Benson AB, Binder E, Cardin DB, Cha C, Chung V, Dillhoff M, Dotan E, Ferrone CR, Fisher G, Hardacre J, Hawkins WG, Ko AH, LoConte N, Lowy AM, Moravek C, Nakakura EK, O'Reilly EM, Obando J, Reddy S, Thayer S, Wolff RA, Burns JL, Zuccarino-Catania G
Abstract
The NCCN Guidelines for Pancreatic Adenocarcinoma discuss the diagnosis and management of adenocarcinomas of the exocrine pancreas and are intended to assist with clinical decision-making. These NCCN Guidelines Insights discuss important updates to the 2019 version of the guidelines, focusing on postoperative adjuvant treatment of patients with pancreatic cancers.
PMID: 30865919 [PubMed - indexed for MEDLINE]
Personal Control Over Decisions to Participate in Research by Persons With Histories of Both Substance Use Disorders and Criminal Justice Supervision.
J Empir Res Hum Res Ethics. 2018 04;13(2):160-172
Authors: Chen DT, Ko TM, Allen AA, Bonnie RJ, Suratt CE, Appelbaum PS, Nunes EV, Friedmann PD, Lee JD, Gordon MS, McDonald R, Wilson D, Boney TY, Murphy SM, O'Brien CP
Abstract
Individuals must feel free to exert personal control over decisions regarding research participation. We present an examination of participants' perceived personal control over, as well as reported pressures and threats from others, influencing their decision to join a study assessing the effectiveness of extended-release naltrexone in preventing opioid dependence relapse. Most participants endorsed a strong sense of control over the decision; few reported pressures or threats. Although few in number, participants' brief narrative descriptions of the pressures and threats are illuminating and provide context for their perceptions of personal control. Based on this work, we propose a useful set of tools to help ascertain participants' sense of personal control in joining research.
PMID: 29460668 [PubMed - indexed for MEDLINE]
Maternal Smoking Before and During Pregnancy and the Risk of Sudden Unexpected Infant Death.
Pediatrics. 2019 04;143(4):
Authors: Anderson TM, Lavista Ferres JM, Ren SY, Moon RY, Goldstein RD, Ramirez JM, Mitchell EA
Abstract
OBJECTIVES: Maternal smoking during pregnancy is an established risk factor for sudden unexpected infant death (SUID). Here, we aim to investigate the effects of maternal prepregnancy smoking, reduction during pregnancy, and smoking during pregnancy on SUID rates.
METHODS: We analyzed the Centers for Disease Control and Prevention Birth Cohort Linked Birth/Infant Death Data Set (2007-2011: 20 685 463 births and 19 127 SUIDs). SUID was defined as deaths at <1 year of age with International Classification of Diseases, 10th Revision codes R95 (sudden infant death syndrome), R99 (ill-defined or unknown cause), or W75 (accidental suffocation or strangulation in bed).
RESULTS: SUID risk more than doubled (adjusted odds ratio [aOR] = 2.44; 95% confidence interval [CI] 2.31-2.57) with any maternal smoking during pregnancy and increased twofold between no smoking and smoking 1 cigarette daily throughout pregnancy. For 1 to 20 cigarettes per day, the probability of SUID increased linearly, with each additional cigarette smoked per day increasing the odds by 0.07 from 1 to 20 cigarettes; beyond 20 cigarettes, the relationship plateaued. Mothers who quit or reduced their smoking decreased their odds compared with those who continued smoking (reduced: aOR = 0.88, 95% CI 0.79-0.98; quit: aOR = 0.77, 95% CI 0.67-0.87). If we assume causality, 22% of SUIDs in the United States can be directly attributed to maternal smoking during pregnancy.
CONCLUSIONS: These data support the need for smoking cessation before pregnancy. If no women smoked in pregnancy, SUID rates in the United States could be reduced substantially.
PMID: 30858347 [PubMed - indexed for MEDLINE]
Emergency department utilization among individuals with idiopathic intracranial hypertension.
Int J Health Care Qual Assur. 2019 Feb 11;32(1):152-163
Authors: Murphy S, Friesner DL, Rosenman R, Waslo CS, Au J, Tanne E
Abstract
PURPOSE: Idiopathic intracranial hypertension (IIH) can be a debilitating disorder that is difficult to identify and treat. Failure to adequately manage IIH symptoms may force patients to present at emergency departments (EDs) seeking symptom relief. The purpose of this paper is to empirically characterize ED use by previously diagnosed IIH patients.
DESIGN/METHODOLOGY/APPROACH: Patients diagnosed with IIH, and who registered with the Intracranial Hypertension Registry by 2014, were solicited for study inclusion. A survey was designed to elicit ED use during the period 2010-2012. Information on demographic and socioeconomic characteristics, IIH signs and symptoms, time since diagnosis, perspectives of ED use and quality of life was collected. Quality of life was assessed using an adaptation of the Migraine-Specific Quality of Life Questionnaire. Data were analyzed using descriptive statistics and nonparametric hypothesis tests.
FINDINGS: In total, 39 percent of IIH patients used emergency services over the study period; those that did used the services intensely. These patients were more likely to be non-white, live in households making less than $25,000 annually, have public insurance and have received a diversional shunt procedure. Patients who used the ED were less likely to live in households making $100,000, or more, annually and have private insurance. Participants who used the ED had significantly lower quality-of-life scores, were younger and had been diagnosed with IIH for less time.
ORIGINALITY/VALUE: ED staff and outside physicians can utilize the information contained in this study to more effectively recognize the unique circumstances of IIH patients who present at EDs.
PMID: 30859875 [PubMed - indexed for MEDLINE]
Far lateral approach to anterior foramen magnum meningiomas - When should condyle be drilled?
Neurol India. 2019 Jan-Feb;67(1):59-60
Authors: Sekhar L, Zeeshan Q
Abstract
PMID: 30860093 [PubMed - indexed for MEDLINE]
Deltamethrin Exposure Daily From Postnatal Day 3-20 in Sprague-Dawley Rats Causes Long-term Cognitive and Behavioral Deficits.
Toxicol Sci. 2019 06 01;169(2):511-523
Authors: Pitzer EM, Sugimoto C, Gudelsky GA, Huff Adams CL, Williams MT, Vorhees CV
Abstract
Pyrethroids are synthetic insecticides that act acutely on voltage gated sodium channels to prolong channel opening and depolarization. Epidemiological studies find that exposure to pyrethroids are associated with neurological and developmental abnormalities in children. The long-term effects of type II pyrethroids, such as deltamethrin (DLM), on development have received little attention. We exposed Sprague-Dawley rats to DLM by gavage at doses of 0, 0.25, 0.5, and 1.0 mg/kg/day from postnatal day (P) 3-20 in a split-litter design. Following behavioral testing as adults, monoamine levels, release, and mRNA were assessed via high performance liquid chromatography, microdialysis, and qPCR, respectively. Long-term potentiation (LTP) was assessed at P25-35. Developmental DLM exposure resulted in deficits in allocentric and egocentric learning and memory, increased startle reactivity, reduced conditioned contextual freezing, and attenuated MK-801 induced hyperactivity compared with controls. Startle and egocentric learning were preferentially affected in males. Deltamethrin-treated rats exhibited increased CA1 hippocampal LTP, decreased extracellular dopamine release by microdialysis, reduced dopamine D1 receptor mRNA expression in neostriatum, and decreased norepinephrine levels in the hippocampus. The data indicate that neonatal DLM exposure has adverse long-term effects on learning, memory, startle, glutamatergic function, LTP, and norepinephrine.
PMID: 30850843 [PubMed - indexed for MEDLINE]
Left Ventricular Thrombus: Contemporary Etiologies, Treatment Strategies, and Outcomes.
J Am Coll Cardiol. 2019 04 23;73(15):2007-2009
Authors: McCarthy CP, Murphy S, Venkateswaran RV, Singh A, Chang LL, Joice MG, Rivero JM, Vaduganathan M, Januzzi JL, Bhatt DL
PMID: 30846340 [PubMed - indexed for MEDLINE]
Underutilization of Cardiac Rehabilitation for Type 2 Myocardial Infarction.
J Am Coll Cardiol. 2019 04 23;73(15):2005-2007
Authors: McCarthy CP, Murphy S, Cohen JA, Rehman S, Jones-O'Connor M, Olshan DS, Singh A, Vaduganathan M, Januzzi JL, Wasfy JH
PMID: 30846342 [PubMed - indexed for MEDLINE]
Immunotherapy for brain tumors: understanding early successes and limitations.
Expert Rev Neurother. 2018 03;18(3):251-259
Authors: Lieberman NAP, Vitanza NA, Crane CA
Abstract
INTRODUCTION: Adverse effects and toxicities related to standard treatments for brain tumors significantly reduce patients' quality of life. Although most immunotherapy approaches for solid tumors have not been successful, several early-phase clinical trials are beginning to reveal a potential role for immunotherapy in the treatment of brain tumors. In particular, methods that activate the innate immune system and induce a polyclonal anti-cancer response have demonstrated that brain tumors are susceptible to immune-mediated tumor destruction. Compared with conventional therapies, modulation of the immune system may improve both survivorship and quality of life during and following treatment. Areas covered: An overview of mechanisms of immunotherapy in the context of current treatments for adult and pediatric brain tumors is provided. Results from recent clinical trials will be discussed, focusing on the favorable safety and efficacy profiles of immunotherapeutics. Expert commentary: Although it is too early to judge the long-term safety of immunotherapy for the treatment of patients with brain tumors, early results suggest that these drugs are well-tolerated and may improve survival and quality of life. Importantly, approaches that activate an anti-tumor immune response lay the framework for iterative development of immunotherapies that can reliably treat patients with brain tumors.
PMID: 29322843 [PubMed - indexed for MEDLINE]
Endovascular thrombectomy in pediatric patients with large vessel occlusion.
J Neurointerv Surg. 2019 Jul;11(7):729-732
Authors: Shoirah H, Shallwani H, Siddiqui AH, Levy EI, Kenmuir CL, Jovin TG, Levitt MR, Kim LJ, Griauzde J, Pandey AS, Gemmete JJ, Abruzzo T, Arthur AS, Elijovich L, Hoit D, Cheema A, Aghaebrahim A, Sauvageau E, Hanel R, Ringer AJ, Nascimento FA, Kan P, Mocco J
Abstract
BACKGROUND: Pediatric acute ischemic stroke with underlying large vessel occlusion is a rare disease with significant morbidity and mortality. There is a paucity of data about the safety and outcomes of endovascular thrombectomy in these cases, especially with modern devices.
METHODS: We conducted a retrospective review of all pediatric stroke patients who underwent endovascular thrombectomy in nine US tertiary centers between 2008 and 2017.
RESULTS: Nineteen patients (63.2% male) with a mean (SD) age of 10.9(6) years and weight 44.6 (30.8) kg were included. Mean (SD) NIH Stroke Scale (NIHSS) score at presentation was 13.9 (5.7). CT-based assessment was obtained in 88.2% of the patients and 58.8% of the patients had perfusion-based assessment. All procedures were performed via the transfemoral approach. The first-pass device was stentriever in 52.6% of cases and aspiration in 36.8%. Successful revascularization was achieved in 89.5% of the patients after a mean (SD) of 2.2 (1.5) passes, with a mean (SD) groin puncture to recanalization time of 48.7 (37.3) min (median 41.5). The mean (SD) reduction in NIHSS from admission to discharge was 10.2 (6.2). A good neurological outcome was achieved in 89.5% of the patients. One patient had post-revascularization seizure, but no other procedural complications or mortality occurred.
CONCLUSIONS: Endovascular thrombectomy is safe and feasible in selected pediatric patients. Technical and neurological outcomes were comparable to adult literature with no safety concerns with the use of standard adult devices in patients as young as 18 months. This large series adds to the growing literature but further studies are warranted.
PMID: 30842301 [PubMed - indexed for MEDLINE]
Nanoparticle Biokinetics in Mice and Nonhuman Primates.
ACS Nano. 2017 09 26;11(9):9514-9524
Authors: Chiarelli PA, Revia RA, Stephen ZR, Wang K, Jeon M, Nelson V, Kievit FM, Sham J, Ellenbogen RG, Kiem HP, Zhang M
Abstract
Despite the preponderance of iron oxide nanoparticles (NPs) designed for theranostic applications, widespread clinical translation of these NPs lags behind. A better understanding of how NP pharmacokinetics vary between small and large animal models is needed to rapidly customize NPs for optimal performance in humans. Here we use noninvasive magnetic resonance imaging (MRI) to track iron oxide NPs through a large number of organ systems in vivo to investigate NP biokinetics in both mice and nonhuman primates. We demonstrate that pharmacokinetics are similar between mice and macaques in the blood, liver, spleen, and muscle, but differ in the kidneys, brain, and bone marrow. Our study also demonstrates that full-body MRI is practical, rapid, and cost-effective for tracking NPs noninvasively with high spatiotemporal resolution. Our techniques using a nonhuman primate model may provide a platform for testing a range of NP formulations.
PMID: 28885825 [PubMed - indexed for MEDLINE]
Functional Status Examination versus Glasgow Outcome Scale Extended as Outcome Measures in Traumatic Brain Injuries: How Do They Compare?
J Neurotrauma. 2019 08 15;36(16):2423-2429
Authors: Dikmen S, Machamer J, Manley GT, Yuh EL, Nelson LD, Temkin NR, TRACK-TBI Investigators
Abstract
Outcome measures are essential components of natural history studies of recovery and treatment effects after traumatic brain injury (TBI). The Glasgow Outcome Scale (GOS) and its revised version, the Glasgow Outcome Scale Extended (GOSE), are well accepted and widely used for both observational and intervention studies, but there are concerns about their psychometric properties and aptness as outcome measures for TBI. The present study compares the Functional Status Examination (FSE) with the GOSE to assess outcome after TBI in a sample of 533 participants with TBI from the Magnesium Sulfate study and the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study by evaluating the sensitivity of each measure to severity of brain injury and recovery of function over time. The results indicate that both measures are strongly correlated with TBI severity. At three months, the correlation strengths between injury severity and each outcome measure do not differ (p = 0.88 for Glasgow Coma Scale [GCS], p = 0.13 for computed tomography [CT] abnormalities) but at six months, the FSE is more strongly related to TBI severity indices than is the GOSE (p = 0.045 for GCS, p = 0.014 for CT abnormalities). In addition, the FSE generally shows significantly more improvement over time than the GOSE (p < 0.001). Detailed, structured administration rules and a wider score range of the FSE likely yields more sensitive and precise assessment of functional level than the GOSE. The FSE may be a valuable alternative to the GOSE for assessing functional outcome after TBI.
PMID: 30827167 [PubMed - indexed for MEDLINE]
Investigating racial disparities in bariatric surgery referrals.
Surg Obes Relat Dis. 2019 Apr;15(4):615-620
Authors: Johnson-Mann C, Martin AN, Williams MD, Hallowell PT, Schirmer B
Abstract
BACKGROUND: Prior studies investigating racial, socioeconomic, and/or insurance disparities with regard to access to care and outcomes in bariatric surgery have been performed with varying results.
OBJECTIVES: Our aim was to determine if racial or ethnic disparities exist in referral patterns for bariatric surgery at a single center.
METHODS: An institutional, retrospective chart review from January 2012 through June 2017 was performed for patients meeting referral criteria to bariatric surgery. Data collection was limited to patients referred to the bariatric surgery clinic from on-site primary care clinics.
RESULTS: In total, 4736 patients were eligible for bariatric surgery during the study period. Patients were 63.8% female (n = 3022), and 36.2% male (n = 1714); 53.9% white (n = 2553), 37.8% black (n = 1790), and 8.3% Hispanic (n = 393). Female patients were more likely to be referred than male patients (5.5% versus 4.1%, χ2 4.59, P = .032). On univariate comparison, Hispanic patients were less likely to be referred compared with black or white patients (2.0% versus 5.3% and 5.2%, χ2 7.88, P = .019).
CONCLUSION: Hispanic patients were less likely to be referred at our institution for bariatric surgery compared with white or black patients. A barrier to referral may be explained by the disproportionate number of Hispanic patients that were designated as "self-pay" rather than private insurance or Medicaid/Medicare coverage that is required for bariatric surgery referral. This finding underscores the need for further research surrounding barriers to access to care for Hispanic patients.
PMID: 30824334 [PubMed - indexed for MEDLINE]
Direct stimulation of somatosensory cortex results in slower reaction times compared to peripheral touch in humans.
Sci Rep. 2019 03 01;9(1):3292
Authors: Caldwell DJ, Cronin JA, Wu J, Weaver KE, Ko AL, Rao RPN, Ojemann JG
Abstract
Direct cortical stimulation (DCS) of primary somatosensory cortex (S1) could help restore sensation and provide task-relevant feedback in a neuroprosthesis. However, the psychophysics of S1 DCS is poorly studied, including any comparison to cutaneous haptic stimulation. We compare the response times to DCS of human hand somatosensory cortex through electrocorticographic grids with response times to haptic stimuli delivered to the hand in four subjects. We found that subjects respond significantly slower to S1 DCS than to natural, haptic stimuli for a range of DCS train durations. Median response times for haptic stimulation varied from 198 ms to 313 ms, while median responses to reliably perceived DCS ranged from 254 ms for one subject, all the way to 528 ms for another. We discern no significant impact of learning or habituation through the analysis of blocked trials, and find no significant impact of cortical stimulation train duration on response times. Our results provide a realistic set of expectations for latencies with somatosensory DCS feedback for future neuroprosthetic applications and motivate the study of neural mechanisms underlying human perception of somatosensation via DCS.
PMID: 30824821 [PubMed - indexed for MEDLINE]
Mild, Redox-Neutral Formylation of Aryl Chlorides through the Photocatalytic Generation of Chlorine Radicals.
Angew Chem Int Ed Engl. 2017 06 12;56(25):7191-7194
Authors: Nielsen MK, Shields BJ, Liu J, Williams MJ, Zacuto MJ, Doyle AG
Abstract
We report a redox-neutral formylation of aryl chlorides that proceeds through selective 2-functionalization of 1,3-dioxolane through nickel and photoredox catalysis. This scalable benchtop approach provides a distinct advantage over traditional reductive carbonylation in that no carbon monoxide, pressurized gas, or stoichiometric reductant is employed. The mild conditions give unprecedented scope from abundant and complex aryl chloride starting materials.
PMID: 28471521 [PubMed - indexed for MEDLINE]
Matricidal cavernous aneurysms: a multicenter case series.
J Neurointerv Surg. 2019 Jun;11(6):584-590
Authors: Dacus MR, Nickele C, Welch BG, Ban VS, Ringer AJ, Kim LJ, Levitt MR, Lanzino G, Kan P, Arthur AS, Endovascular Neurosurgery Research Group (ENRG)
Abstract
BACKGROUND: Cavernous carotid artery aneurysms (CCAs) represent a unique subset of intracranial aneurysms due to their distinct natural history and the anatomy of the cavernous sinus. Enlarging CCAs can cause elastic compression of the parent internal carotid artery (ICA). We suggest defining aneurysms that cause luminal stenosis of their parent vessels as 'matricidal aneurysms.'Though many patients are asymptomatic, presenting symptoms of CCAs include ophthalmoplegia with resulting diplopia, vision changes, pain, ptosis, facial numbness, and cavernous-carotid fistula. Less commonly, patients with CCAs can present with epistaxis, subarachnoid hemorrhage, and-in cases of matricidal aneurysms-ischemia due to stenosis. The proper management of stenosis caused by a matricidal CCA is not well established and may not be intuitive.
METHODS: We present a multicenter retrospective case series of patients with matricidal CCAs.
RESULTS: Forty patients with matricidal aneurysms presented with both asymptomatic and symptomatic stenosis. These patients were either treated with conservative medical management, coiling, flow diversion, or endovascular sacrifice of the parent artery. Planned treatment modalities were not executed in 11 cases (28% treatment failure rate). Presenting symptoms, patient outcomes, and follow-up data are presented for all cases.
CONCLUSION: Matricidal aneurysms require careful consideration and planning. The restricted anatomy of the cavernous sinus can make successful execution of endovascular interventions more difficult. Direct elastic compression of the parent artery does not respond to angioplasty and stenting in the same way atherosclerotic stenosis does. Because of this, planning for the possibility of parent vessel sacrifice is important.
PMID: 30814330 [PubMed - indexed for MEDLINE]
siRNA rescues nonhuman primates from advanced Marburg and Ravn virus disease.
J Clin Invest. 2017 12 01;127(12):4437-4448
Authors: Thi EP, Mire CE, Lee AC, Geisbert JB, Ursic-Bedoya R, Agans KN, Robbins M, Deer DJ, Cross RW, Kondratowicz AS, Fenton KA, MacLachlan I, Geisbert TW
Abstract
Ebolaviruses and marburgviruses belong to the family Filoviridae and cause high lethality in infected patients. There are currently no licensed filovirus vaccines or antiviral therapies. The development of broad-spectrum therapies against members of the Marburgvirus genus, including Marburg virus (MARV) and Ravn virus (RAVV), is difficult because of substantial sequence variability. RNAi therapeutics offer a potential solution, as identification of conserved target nucleotide sequences may confer activity across marburgvirus variants. Here, we assessed the therapeutic efficacy of lipid nanoparticle (LNP) delivery of a single nucleoprotein-targeting (NP-targeting) siRNA in nonhuman primates at advanced stages of MARV or RAVV disease to mimic cases in which patients begin treatment for fulminant disease. Sixteen rhesus monkeys were lethally infected with MARV or RAVV and treated with NP siRNA-LNP, with MARV-infected animals beginning treatment four or five days after infection and RAVV-infected animals starting treatment three or six days after infection. While all untreated animals succumbed to disease, NP siRNA-LNP treatment conferred 100% survival of RAVV-infected macaques, even when treatment began just 1 day prior to the death of the control animals. In MARV-infected animals, day-4 treatment initiation resulted in 100% survival, and day-5 treatment resulted in 50% survival. These results identify a single siRNA therapeutic that provides broad-spectrum protection against both MARV and RAVV.
PMID: 29106386 [PubMed - indexed for MEDLINE]
Three-Dimensional Planning Tool for Breast Conserving Surgery: A Technological Review.
Crit Rev Biomed Eng. 2018;46(6):523-580
Authors: Oliveira SP, Morgado P, Gouveia PF, Teixeira JF, Bessa S, Monteiro JP, Zolfagharnasab H, Reis M, Silva NL, Veiga D, Cardoso MJ, Oliveira HP, Ferreira MJ
Abstract
Breast cancer is one of the most common malignancies affecting women worldwide. However, despite its incidence trends have increased, the mortality rate has significantly decreased. The primary concern in any cancer treatment is the oncological outcome but, in the case of breast cancer, the surgery aesthetic result has become an important quality indicator for breast cancer patients. In this sense, an adequate surgical planning and prediction tool would empower the patient regarding the treatment decision process, enabling a better communication between the surgeon and the patient and a better understanding of the impact of each surgical option. To develop such tool, it is necessary to create complete 3D model of the breast, integrating both inner and outer breast data. In this review, we thoroughly explore and review the major existing works that address, directly or not, the technical challenges involved in the development of a 3D software planning tool in the field of breast conserving surgery.
PMID: 30806213 [PubMed - indexed for MEDLINE]
Preclinical Models of Alzheimer's Disease: Relevance and Translational Validity.
Curr Protoc Pharmacol. 2019 03;84(1):e57
Authors: Mullane K, Williams M
Abstract
The only drugs currently approved for the treatment of Alzheimer's Disease (AD) are four acetylcholinesterase inhibitors and the NMDA antagonist memantine. Apart from these drugs, which have minimal to no clinical benefit, the 40-year search for effective therapeutics to treat AD has resulted in a clinical failure rate of 100% not only for compounds that prevent brain amyloid deposition or remove existing amyloid plaques but also those acting by a variety of other putative disease-associated mechanisms. This indicates that the preclinical data generated from current AD targets to support the selection, optimization, and translation of new chemical entities (NCEs) and biologics to clinical trials is seriously compromised. While many of these failures reflect flawed hypotheses or a lack of adequate characterization of the preclinical pharmacodynamic and pharmacokinetic (PD/PK) properties of lead NCEs-including their bioavailability and toxicity-the conceptualization, validation, and interrogation of the current animal models of AD represent key limitations. The overwhelming majority of these AD models are transgenic, based on aspects of the amyloid hypothesis and the genetics of the familial form of the disease. As a result, these generally lack construct and predictive validity for the sporadic form of the human disease. The 170 or so transgenic models, perhaps the largest number ever focused on a single disease, use rodents, mainly mice, and in addition to amyloid also address aspects of tau causality with more complex multigene models including other presumed causative factors together with amyloid. This overview discusses the current animal models of AD in the context of both the controversies surrounding the causative role of amyloid in the disease and the need to develop validated models of cognitive function/dysfunction that more appropriately reflect the phenotype(s) of human aged-related dementias. © 2019 by John Wiley & Sons, Inc.
PMID: 30802363 [PubMed - indexed for MEDLINE]
