News Release

NYU Langone researchers to present new findings at 2015 Alzheimer's Association Conference

Peer-Reviewed Publication

NYU Langone Health / NYU Grossman School of Medicine

(New York, July 18, 2015) Researchers from the NYU Langone Medical Center, NYU School of Medicine will present new findings at the 2015 Alzheimer's Association International Conference in Washington, D.C., July 18-23-2015.

The NYU Langone Alzheimer's Disease Center is comprised of the Center for Cognitive Neurology, Center for Brain Health and the Parkinson's and Movement Disorders Center.

The Center for Cognitive Neurology at NYU Langone is a multidisciplinary, integrated center devoted to research, clinical care and clinical advances toward the treatment and cure of neurological diseases affecting cognition -- focused on memory, language, attention, auditory, visual and thinking difficulties. The Center is comprised of the Silberstein Alzheimer's Institute which houses the NYU Alzheimer's Disease Center (ADC) and the Pearl I. Barlow Center for Memory Evaluation and Treatment; and basic, translational and clinical research is conducted within more than 20 major NYU centers, programs and laboratories. The focus is on improving the understanding and treatment of diseases and injuries to the nervous system. Neurologists and neuroscientists conduct research in the risks, predictors, prevention, diagnostic tests and potential treatments for Alzheimer's disease (AD), Lewy Body dementia (LBD), vascular dementia, prion disease, mild cognitive impairment, and other related conditions, and have expertise in evaluating, diagnosing and treating individuals with brain conditions that affect memory and/or thinking (cognition).

At NYU Langone, our research programs and clinical care centers are devoted to the prevention, treatment and cure of Alzheimer's disease, Lewy body dementia, prion diseases, vascular dementia, traumatic brain injury, frontotemporal dementia and other neurodegenerative conditions. Patients with these conditions and other memory disorders are seen at the Pearl I. Barlow Center for Memory Evaluation & Treatment.

We will be happy to provide full copies of the presentations, abstract and posters. Our researchers are available for comment on their research and other breaking news topics, can be reached in D.C.

Wednesday, July 22, 2015 at 9:30-a.m. - 4:15 p.m.ET - Poster Session, Therapeutics: Preclinical

Abstract # 5364: "Monoclonal Antibodies that Recognize Oligomeric Tau and Aβ, also Recognize Pathological Structures in Parkinson's disease Human Brains"
EMBARGOED UNTIL 7/19, 2013 at 9:30 AM.ET Highlighted by Alzheimer's Association in Press Release
Fernando Goñi*, Krystal Herline, Eleanor Drummond, Mitchell Marta-Ariza, Frances Prelli, Thomas Wisniewski

Presenting author: Fernando Goni, PhD, Research Associate Professor of Neurology, NYU Langone Medical Center

Background: It has been increasingly recognized that the pathogenesis of many neurodegenerative diseases is related to the accumulation of diverse proteins in aggregated/oligomeric forms. The pathological conformers can spread to different areas of the brain via a "prion-like" conversion mechanism mediated by the mobile β-sheet oligomeric structure of each particular peptide or protein. Previously we have characterized conformational monoclonal antibodies that react to both oligomers of Aβ and tau in AD, as well as to prion disease proteins. We have now determined their binding specificity and capacity to be extended to synthetic oligomers of α-synuclein and to pathological intracellular structures present in Lewy body containing neurons of Parkinson's disease (PD) subjects.

Conclusions: Conformational monoclonal antibodies that are well characterized to react against pathological conformers in AD human brains and that can produce amelioration of existing AD pathology in AD animal models can also recognize oligomeric forms of α-synuclein and intraneuronal structures associated with Lewy bodies. Monoclonal antibodies that are specific for pathology associated conformations are good candidates to be used as immunotherapeutic agents alone or in combination with other approaches in many neurodegenerative diseases including Parkinson's disease.

Monday, July 20, 2015 at 9:30-a.m. - 4:15 p.m.ET - Poster Session, Therapeutics: Preclinical

Abstract #5357: "Active vaccination of old Alzheimer's Disease transgenic animals with oligomeric polymerized pBri and CpG ODN can reverse preexisting AD pathology"
Fernando Goñi*, Henrieta Scholtzova, Mitchell Marta-Ariza, Krystal Herline, Yanjie Sun, Jason Pan, Pankaj Mehta, Thomas Wisniewski

*Presenting author: Fernando Goni, PhD, Research Associate Professor of Neurology, NYU Langone Medical Center

Background: We have previously demonstrated that immuno-intervention in AD animal models can lead to prevention of some pathology through innate immune system stimulation via TLR9 induced by CpG ODN (Scholtzova et al 2014) or the modulation of the adaptive immune system through active vaccination with the β-sheet oligomeric form of the polymerized Bri peptide (Goni et al 2014). A challenge to therapeutic immune stimulation of old AD Tg animals, with preexisting extensive pathology, is senescence of the immune system. We have now vaccinated old 3xTg AD animals with both Aβ and tau pathology, with the pBri as a conformational antigen and CpG ODN as an immune stimulator.

Conclusions: The active immunomodulation using polymerized β-sheet oligomeric pBri can elicit a conformational antibody response even in old animals. These antibodies directed to β-sheet conformation can retard the progression and reverse some preexisting pathology. The use of CpG ODN can help to boost the innate immune system, in senescent animals, to help establish the subsequent adaptive conformational response.

Monday, July 20, 2015 at 2:00 p.m. - 3:30p.m.ET - Oral Presentation

Abstract #6325: "Efficacy of Internet-Based Training of Clinicians to Implement an Evidence-Based Intervention for Dementia Caregivers"
Mary S. Mittelman, DrPH*, Cynthia Epstein, LCSW and John V Hobday, MS

*Presenting author: Mary Mittelman, DPH, research professor, Departments of Psychiatry and Rehabilitation Medicine, NYU Langone Medical Center

Background: As the number of people with dementia increases, there is a growing need for trained providers of evidence-based interventions to support family caregivers. A 20-year randomized controlled trial demonstrated many benefits of the NYU Caregiver Intervention (NYUCI) -- reduced caregiver depression and stress and improved physical health, and delayed nursing home placement of the person with dementia. The intervention has been widely implemented, but until now, clinician training was provided in person by the original investigator and an expert counselor. Online training, if equally effective, would provide a technological solution, accessible 24/7, reducing cost and increasing accessibility.

Conclusions: While there are challenges in assuring high rates of completion, Internet-based training in implementing an evidence-based caregiver intervention can be as effective as in person training for social service providers, is more accessible and cost-effective and can lead to widespread availability of a skilled workforce to support family caregivers.

Monday, July 20, 2015 at 9:30 a.m. - 4:15p.m. ET- Poster Session

Abstract #1945: " Effects of a Comprehensive, Individualized Person Centered Management Program on Persons with Moderately Severe Alzheimer's Disease (AD): A Randomized Controlled Trial: Comprehensive Study Findings"
Barry Reisberg, MD; Isabel Monteiro, MD; Carol Torossian, Psy.D.; Jinfeng Xu, Ph.D.; Khurram Janjua, MD; Santosh Ghimire, MD; Kathryn Sommese, B.A. and Sunnie Kenowsky, D.V.M.

*Presenting author: Barry Reisberg, M.D., professor of psychiatry, Clinical Director, Aging and Dementia Clinical Research Center, NYU Langone Medical Center

Background: Persons with moderately severe AD are the most distressed AD persons (Reisberg, et al., Bull Clin Neurosci, 1989). We described some needs and potential solutions for these persons in a "science of AD management" (Reisberg, et al., Am J Alzheimers Dis Other Demen, 2002). Subsequently, memantine, the first medication for advanced AD, demonstrated efficacy. We therefore investigated a Comprehensive Individualized Person Centered Management Program (CI-PCM) in addition to memantine treatment, in moderately severe AD persons.

Conclusions: The present results are consonant with observations we previously reported with the NYU CIBIC-Plus in which subscale analyses also indicated robust effects of the CI-PCM intervention on functioning and behavior, but not cognition. The NYU CIBIC-Plus clinician raters were different from and blind to the raters' evaluations of the results reported herein. Hence, it is clear that the CI-PCM program, from multiple rater perspectives, and multiple assessments, produces robust positive effects on functioning and behavior. These results are of great potential significance for AD persons and their caregivers.

Monday, July 20, 2015 at 9:30 a.m. - 4:15p.m. ET - Poster Session, Therapeutics: Preclinical

Abstract #3725: "Toll-like Receptor 9 Stimulation Via CpG ODN in a Non-Human Primate Model of Sporadic Cerebral Amyloid Angiopathy"
Henrieta Scholtzova, MD, PhD; Pramod N Nehete, PhD; Bharti P Nehete, MS; Melanie M Mallory, MS; Elizabeth Cho, MS; Andrea Holmes, MS; Jina Park, MS; Melinda S Wren, MS; Paige Pardington, MS; Goutam Gupta, PhD; Pankaj D Mehta, PhD; Lawrence E Williams, PhD and Thomas Wisniewski, MD,

*Presenting author: Henrieta Scholtzova, MD, PhD, Research Assistant Professor of Neurology, Center for Cognitive Neurology, NYU Langone Medical Center

Background: Immunomodulation is a promising therapeutic approach for Alzheimer's disease (AD); however, major drawbacks are cerebral microhemorrhages associated with increased cerebral amyloid angiopathy (CAA) and excessive inflammation. Our initial findings indicate that stimulation of TLR9 signaling with CpG oligodeoxynucleotide (ODN) is effective against CAA without inducing toxicity in AD mouse models. To further assess potential human use of CpG ODN we advanced our studies using a well-established non-human primate model of sporadic CAA, squirrel monkey (Saimiri Boliviensis).

Conclusions: The presented studies represent the first trial of specifically targeting CAA in non-human primates. We hope that our research will validate this novel approach of immunomodulation as a safer method to successfully ameliorate AD related pathologies and provide critical data for potential clinical use of CpG ODN in AD patients.

Wednesday, July 22, 2015 at 9:30 a.m. - 4:15p.m.ET - Poster Session, Developing Topics

Abstract # 6067: "Methazolamide Protects Neuronal and Glial Cells from Amyloid Toxicity in Vitro and in Vivo Via Mitochondria-Mediated Mechanisms."
Silvia Fossati, PhD; Patrizia Giannoni, PhD; Maria E Solesio, PhD; Sarah L Cocklin, PhD; Erwin Cabrera; Jorge Ghiso, PhD and Agueda Rostagno, PhD,

*Presenting author: Silvia Fossati, PhD, Research Assistant Professor of Neurology, Center for Cognitive Neurology, NYU Langone Medical Center

Background: Neurodegeneration and memory loss in Alzheimer's disease (AD) have been associated in many reports with mitochondrial dysfunction. Molecular pathways triggered by mitochondrial deregulation, with associated production of reactive oxygen species and release of pro-apoptotic factors, are thought to be early events in the pathogenesis of the disease. Carbonic anhydrase inhibitors such as methazolamide (MTZ) are FDA approved for glaucoma as well as other indications, and have been considered as potential therapeutic strategies in models of Huntington's disease, stroke, muscular dystrophy and diabetes.

Conclusions: Our results demonstrate the efficacy of MTZ in in vitro and in vivo models of amyloid-mediated toxicity, delineating the molecular mechanism of action of the compound and providing the first evidence in support of the possibility of a new therapeutic approach for AD.

Wednesday, July 22, 2015 at 9:30 a.m. - 4:15p.m.ET - Poster Session, Developing Topics

Abstract # 6198: "CSF AB42 Levels May Increase Due to Age-Dependent Slow-Wave Sleep Loss Prior to Amyloid Deposition in Humans."
Osorio RS, Wohlleber M, Ducca E, Gumb T, Parekh A, Barclay K, Varga AW, Burschtin O, Ayappa I, Rapoport DM, de Leon MJ

*Presenting author: Ricardo Osorio, MD, MA, research assistant professor, Department of Psychiatry, Center for Cognitive Neurology, NYU Langone Medical Center

Background: Recently, several studies have provided evidence that Aβ dynamics are influenced by the sleep-wake cycle. In transgenic mice, soluble Aβ levels are higher in the interstitial space during wakefulness and lower during sleep, while sleep deprivation increases Aβ concentrations and accelerates Aβ plaque deposition. In humans, in a study where serial cerebrospinal fluid (CSF) samples were collected for 36 hours, Aβ42 concentrations fluctuated with a diurnal pattern, with the lowest Aβ42 levels in the morning sampling. This CSF Aβ diurnal pattern has been related to higher synaptic activity during wakefulness and decreased synaptic activity during slow wave sleep (SWS). In the elderly, brain soluble Aβ42 levels may be relatively increased as a result of: a) age-dependent loss of SWS; and, b) sleep disturbances common in late-life that disrupt SWS. The present study examined whether SWS was associated with CSF Aβ42 levels in a morning lumbar puncture (LP) performed between 11:00 AM-01:00 PM.

Conclusions: In the absence of AD pathology, reduced %SWS or SWA are associated with increases in CSF Aβ42.

Wednesday, July 22, 2015 at 9:30 a.m. - 4:15p.m. ET- Poster Session

Abstract #6212: "Effects of Vascular Risk Factors and Medications on PiB Deposition in Cognitively Normal Subjects"
Lidia Glodzik, MD, PhD; Henry Rusinek, PhD; Elizabeth Pirraglia, MS; Wai Tsui, MS; Lisa Mosconi; Yi Li; Pauline McHugh, MD; John Murray; Schantel Williams, RN; Catherine Randall, MA; Tracy Butler, MD1; Anup Deshpande, MD; Shankar Vallabhajosula, PhD

*Presenting author: Lidia Glodzik, MD, PhD; assistant research professor of neurology, Center for Cognitive Neurology, NYU Langone Medical Center

Background: Metabolic syndrome (MetS) is a multiplex risk factor for cardiovascular disease that deserves significant attention. While there is a growing recognition of the link between MetS and cognition, little is known about how MetS relates to cortical amyloid deposition. The detection of vascular risk is commonly followed by an introduction of appropriate treatment aimed at risk modification. The treatment itself may affect accumulation of brain amyloid, but this issue is largely unknown. Our aim was to assess the relationships between MetS, antihypertensive and antilipid medications, and cortical amyloid binging of Pittsburgh compound B (PiB) in cognitively healthy adults and elderly.

Conclusions: ARBs and diuretics were associated with less amyloid deposition. Prospective studies should confirm this benefit of antihypertensive drugs and establish whether such modifications translate into measurable clinical outcomes. Women may be particularly sensitive to detrimental effects of obesity on the aging brain. This must be taken into consideration while planning future interventions.

Ralph A. Nixon, MD, PhD, will be honored at the AAIC meeting. Dr. Nixon is recipient of the 2015 Zaven Khachaturian Award. Named in honor of noted neuroscientist and a pioneer in Alzheimer's disease research, Zaven Khachaturian, PhD, this award recognizes an individual whose compelling vision, selfless dedication, and most extraordinary achievement has significantly advanced the field of Alzheimer's disease science. His work is the first to call attention to the importance of proteases in Alzheimer's disease. His recent studies have identified defects in the clearance and recycling of proteins in brain cells, which are critical to Alzheimer's pathogenesis and are considered promising targets for therapy of the disease.

Ralph A. Nixon, MD, PhD, will be honored at the AAIC meeting. Dr Nixon is recipient of the 2015 Zaven Khachaturian Award which will be presented on Wednesday, July 22, 10:10-10:30 am at the start of the Plenary session, Washington Convention Center, Hall E. Dr. Nixon is currently a professor of psychiatry and cell biology at NYU Langone Medical Center; Director of Research and Director of the Center for Dementia Research at the Nathan S. Kline Institute for Psychiatric Research.


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