Taub Institute: Genomics Core
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TaubCONNECT Research Perspectives:
July 2016

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» #1 Neuronal activity enhances tau propagation and tau pathology

» #2 Sleep Disordered Breathing and White Matter Hyperintensities in Community-Dwelling Elders

» #1 White Matter Integrity as a Mediator in the Relationship between Dietary Nutrients and Cognition in the Elderly

» #2 Dementia Risk and Protective Factors Differ in the Context of Memory Trajectory Groups

» #1 White Matter Hyperintensities are a Core Feature of Alzheimer's Disease: Evidence From the Dominantly Inherited Alzheimer Network

» #2 Parkinson's Disease: Guilt by Genetic Association

» #1 PDE5 Exists in Human Neurons and is a Viable Therapeutic Target for Neurologic Disease

» #2 PP2A Methylation Controls Sensitivity and Resistance to β-Amyloid–Induced Cognitive and Electrophysiological Impairments

» #1 Tau-driven 26S Proteasome Impairment and Cognitive Dysfunction can be Prevented Early in Disease by Activating cAMP-PKA Signaling

» #2 Older Adults with Poor Self-rated Memory have less Depressive Symptoms and Better Memory Performance when Perceived Self-efficacy is High

» #1 Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory

» #2 Examining the Pathways Between Self-Awareness and Well-Being in Mild to Moderate Alzheimer Disease

» #3 Mediterranean Diet and Brain Structure in a Multiethnic Elderly Cohort

» #1 Progression of Extrapyramidal Signs in Alzheimer's Disease: Clinical and Neuropathological Correlates

» #2 Telomere Longitudinal Shortening as a Biomarker for Dementia Status of Adults With Down Syndrome

» #1 The Reference Ability Neural Network Study: Life-time stability of reference-ability neural networks derived from task maps of young adults

» #2 Novel Selective Calpain 1 Inhibitors as Potential Therapeutics in Alzheimer's Disease

» #1 First Place: DREADDs Activation in the Medial Entorhinal Cortex (MEC) of EC-Tau Mice

» #1 First Place: Amyloid Precursor Protein (APP) is Ubiquitinated at Multiple Sites in the COOH-Terminal Domain as a Signal for Endosomal Sorting

» #1 F-box/LRR-repeat protein 7 is genetically associated with Alzheimer's disease

» #2 The keystone of Alzheimer pathogenesis might be sought in Aβ physiology

» #1 Stereotaxic Infusion of Oligomeric Amyloid-beta into the Mouse Hippocampus

» #2 Brain Amyloid Deposition and Longitudinal Cognitive Decline in Nondemented Older Subjects: Results from a Multi-Ethnic Population

» #1 Candidate genes for Alzheimer's disease are associated with individual differences in plasma levels of beta amyloid peptides in adults with Down syndrome

» #2 Gene-Wise Association of Variants in Four Lysosomal Storage Disorder Genes in Neuropathologically Confirmed Lewy Body Disease

» #1 SUMO1 Affects Synaptic Function, Spine Density and Memory

» #2 Connectivity and Circuitry in a Dish Versus in a Brain

» #1 Making Cognitive Latent Variables Manifest: Distinct Neural Networks For Fluid Reasoning And Processing Speed

» #2 Functional Network Mediates Age-related Differences in Reaction Time: a Replication and Extension Study

» #3 Self-Efficacy Buffers the Relationship between Educational Disadvantage and Executive Functioning

» #1 Specific Downregulation of Hippocampal ATF4 Reveals a Necessary Role in Synaptic Plasticity and Memory

» #2 Mediterranean Diet and Leukocyte Telomere Length in a Multi-ethnic Elderly Population

» #1 Cerebellum can serve as a pseudo-reference region in Alzheimer's disease to detect neuroinflammation measured with PET radioligand binding to translocator protein (TSPO)

» #2 Assembly and Interrogation of Alzheimer's Disease Genetic Networks Reveal Novel Regulators of Progression

» Neurotherapeutics: Rethinking Alzheimer's Disease Therapies

» #1 Dysregulation of microRNA-219 promotes neurodegeneration through post-transcriptional regulation of tau

» #2 Olfactory deficits predict cognitive decline and Alzheimer dementia in an urban community

» #3 Increased permeability-glycoprotein inhibition at the human blood-brain barrier can be safely achieved by performing PET during peak plasma concentrations of tariquidar

» Regulation of synaptic plasticity and cognition by SUMO in normal physiology and Alzheimer's disease

» Lobar Microbleeds Are Associated with a Decline in Executive Functioning in Older Adults

» Targeting Axonal Protein Synthesis in Neuroregeneration and Degeneration

» Inbreeding among Caribbean Hispanics from the Dominican Republic and its effects on risk of Alzheimer disease

» Coding mutations in SORL1 and Alzheimer's disease

» First Place: Pathogenic Role of Formin-mediated Stable Detyrosinated
     Microtubule Inductionby Amyloid beta

» First Place: Differential responsiveness to entorhinal cortical input distinguishes CA1 pyramidal neuron subpopulations

» Soluble amyloid beta levels are elevated in the white matter of Alzheimer's patients, independent of cortical plaque severity

» A Time Course Analysis of the Electrophysiological Properties of Neurons Differentiated from Human Induced Pluripotent Stem Cells (iPSCs)

» Axonally Synthesized ATF4 Transmits a Neurodegenerative Signal across Brain Regions

» Olfactory Dysfunction in the Elderly: Basic Circuitry and Alterations with Normal Aging and Alzheimer's Disease

» Neurological disorders: Quality-control pathway unlocked

» Estrogen Receptor β Variants Modify Risk for Alzheimer's Disease in a Multiethnic Female Cohort

» Combined suppression of CASP2 and CASP6 protects retinal ganglion cells from apoptosis and promotes axon regeneration through CNTF-mediated JAK/STAT signalling and Guidelines

» Local synthesis of TC10 is required for membrane expansion during axon outgrowth

» Dynamin 1 is Required for Memory Formation

» Behavioral Assays with Mouse Models of Alzheimer's Disease: Practical Considerations and Guidelines

» Biobanked Alzheimer's Brain Tissue Yields Living Neurons

» Picomolar Amyloid-ß Peptides Enhance Spontaneous Astrocyte Calcium Transients

Alzheimer's Association International Conference (AAIC 2016)

Earlier this week, thousands of dementia researchers, clinicians, and care providers from around the globe gathered together in Toronto for the annual Alzheimer's Association International Conference (AAIC 2016). Each year, Taub faculty members travel to this event to share and learn of new research in the field, and to network with like-minded colleagues. Below are several highlights from Taub faculty participation at this year's conference (in random order):

Dr. Yaakov Stern initiated the first Professional Interest Area (PIA) on "Reserve, Resilience, and Protective Factors in Alzheimer's disease," and chaired the data blitz for this PIA, which focused on epidemiologic, clinical/neuropsychological, and neuroimaging/biomarker approaches to understanding reserve, with a major emphasis on potential underlying structural and functional brain mechanisms. This new, collaborative undertaking is as part of the AA's International Society to Advance Alzheimer's Research and Treatment (ISTAART), a professional society aimed at strengthening scientific knowledge through greater collaboration among researchers and clinicians with shared PIAs. Dr. Hwamee Oh also participated in this PIA.

Dr. Sandra Barral Rodriguez presented work done by she and Dr. Badri Vardarajan, as team members in the Alzheimer's Disease Sequencing Project (ADSP) Family Working Group, at a featured research session on the ADSP. Their work in this group is focused on the analysis of whole genome sequencing data generated from ethnically diverse families multiply affected by Late Onset Alzheimer's Disease (LOAD). Dr. Barral reported on the results obtained from whole genome sequencing performed on 111 multiethnic LOAD families, with admixture mapping also carried out on Hispanic pedigrees. These results suggest that both coding and non-coding rare variants influence LOAD susceptibility, and show the continued utility of family-based approaches. Variants identified are currently being validated using orthogonal technologies, and follow-up analyses are being conducted.

Badri N. Vardarajan, PhD, MS

Dr. Badri Vardarajan chaired a session on the Genetics of LOAD, which included his own presentation, "Whole Exome Sequencing in Healthy Elderly Apoe ε44 Subjects to Identify Protective Variants in Alzheimer's Disease." This study of Caribbean Hispanic families multiply affected by LOAD revealed a protective variant segregating with APOE ε4 carriers in three large families. To further increase power, Badri and colleagues are conducting sequencing on 200 unaffected APOE ε4 carriers from the same population. Identifying coding sequence variants in LOAD will facilitate the creation of tractable models for investigation of disease related mechanisms and potential therapies.

Dr. Adam Brickman presented a study that examined whether the presence of cerebral microbleeds, a marker of cerebral amyloid angiopathy (CAA), mediates the relationship between white matter hyperintensities (WMH) and estimated symptom onset in individuals with and without autosomal dominant mutations for AD from the Dominantly Inherited Alzheimer's Network (DIAN). Although there was some co-dependency between WMH and cerebral microbleeds, the observed increases in WMH among mutation carriers did not appear to be fully mediated by this marker of CAA. The findings highlight the possibility that WMH represent a core feature of AD independent of vascular forms of beta amyloid.

Dr. Yian Gu presented a study on diet and hippocampal atrophy that was co-authored by multiple Taub faculty members. The study, "Mediterranean diet is associated with slower rate of hippocampal atrophy: a longitudinal study in cognitively normal older adults," showed that, compared to those with low adherence to a Mediterranean diet (MeDi), those with middle and high level of adherence to MeDi had slower rate of decline in hippocampal volume.

Dr. Hwamee Oh presented a study examining whether extraversion and neuroticism are related to the level of beta-amyloid (Aβ) deposition, a pathological hallmark of AD. Results suggest that extraversion, possibly through lifestyle factors, correlates with lower Aβ deposition and better memory functions in cognitively normal elderly. Neuroticism, however, was not associated with either Aβ deposition or cognitive performance. Future studies need to address a causal relationship between personality and the vulnerability to AD-related pathology.

Drs. William C. Kreisl and Seonjoo Lee each presented studies which, as described by the AAIC, evaluated changes in odor identification as an early predictor of cognitive decline, or of the transition to dementia, and compared it to two established biological markers for cognitive decline and dementia: brain amyloid PET imaging and thickness of the brain's cortex in areas important to memory. These studies were also featured on the CUMC Newsroom, and widely distributed by the media this week.

Aging and Dementia Fellow Dr. Anjali Patel presented on the "Prediction of Relapse Following Discontinuation of Antipsychotic Treatment in Alzheimer's Disease: The Role of Hallucinations," co-authored by Drs. Devangere Devanand, Seonjoo Lee, Gregory Pelton, and others. Results suggest that, for patients with severe hallucinations, particularly auditory hallucinations, antipsychotic discontinuation may not be advisable because of high relapse risk.

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