Taub Institute: Genomics Core
AN NIA-FUNDED ALZHEIMER'S DISEASE RESEARCH CENTER
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TaubCONNECT Research Perspectives:
July 2019



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June 2019:

» #1 CpGā€Related SNPs in the MS4A Region Have a Doseā€Dependent Effect on Risk of Lateā€“Onset Alzheimer Disease

» #2 MFN2 Mutations in Charcotā€“Marieā€“Tooth Disease Alter Mitochondria-Associated ER Membrane Function but Do Not Impair Bioenergetics


May 2019:

» #1 Association of Variants in PINX1 and TREM2 With Late-Onset Alzheimer Disease

» #2 Brain Biomarkers and Cognition Across Adulthood


April 2019:

» #1 Predicting Cognitive Improvement in Normal Pressure Hydrocephalus Patients Using Preoperative Neuropsychological Testing and Cerebrospinal Fluid Biomarkers

» #2 Brain Arterial Dilatation and the Risk of Alzheimer's Disease


March 2019:

» #1 Elevated Cellular Cholesterol in Familial Alzheimer's Presenilin 1 Mutation is Associated with Lipid Raft Localization of Ī²-Amyloid Precursor Protein

» #2 FDG-PET Patterns Associated with Underlying Pathology in Corticobasal Syndrome


February 2019:

» #1 Effect of Aerobic Exercise on Cognition in Younger Adults: A Randomized Clinical Trial

» #2 Exercise-linked FNDC5/Irisin Rescues Synaptic Plasticity and Memory Defects in Alzheimerā€™s Models


January 2019:

» #1 A Tau Homeostasis Signature Is Linked with the Cellular and Regional Vulnerability of Excitatory Neurons to Tau Pathology

» #2 Between-network Functional Connectivity Is Modified by Age and Cognitive Task Domain


December 2018:

» #1 Epigenome-Wide Study Uncovers Large-Scale Changes in Histone Acetylation Driven by Tau Pathology in Aging and Alzheimerā€™s Human Brains

» #2 Semantic Network Function Captured by Word Frequency in Nondemented APOE Īµ4 Carriers


November 2018:

» First Place: NSUN2 is Dysregulated in Alzheimer's Disease

» First Place: High-throughput Disease Modeling to Uncover Shared and Unique Characteristics Among Neurodegenerative Diseases


October 2018:

» #1 Homeostatic Plasticity Scales Dendritic Spine Volumes and Changes the Threshold and Specificity of Hebbian Plasticity

» #2 An MRI Measure of Degenerative and Cerebrovascular Pathology in Alzheimer Disease

» #3 Integrative Transcriptome Analyses of the Aging Brain Implicate Altered Splicing in Alzheimer's Disease Susceptibility


September 2018:

» #1 Clinical Experience with Cerebrospinal Fluid AĪ²42, Total and Phosphorylated Tau in the Evaluation of 1,016 Individuals for Suspected Dementia

» #2 Evaluation of TDP-43 Proteinopathy and Hippocampal Sclerosis in Relation to APOE Īµ4 Haplotype Status: A Community-Based Cohort Study


August 2018:

» #1 A Multi-Omic Atlas of the Human Frontal Cortex for Aging and Alzheimer's Disease Research

» #2 An Alzheimer's Linked Loss-of-Function CLN5 Variant Impairs Cathepsin D Maturation Consistent with a Retromer Trafficking Defect

» #3 Letter and Category Fluency Performance Correlates with Distinct Patterns of Cortical Thickness in Older Adults


July 2018:

» #1 Activating Transcription Factor 4 (ATF4) Regulates Neuronal Activity by Controlling GABABR Trafficking

» #2 Whole-exome Sequencing in 20,197 Persons for Rare Variants in Alzheimer's Disease


June 2018:

» #1 Excess Synaptojanin 1 Contributes to Place Cell Dysfunction and Memory Deficits in the Aging Hippocampus in Three Types of Alzheimer's Disease

» #2 Preparation of Tau Oligomers After the Protein Extraction from Bacteria and Brain Cortices


May 2018:

» #1 Whole Genome Sequencing in Caribbean Hispanic Families Associated with Late-Onset Alzheimer's Disease (LOAD)

» #2 Oligomeric AĪ²1-42 Triggers the Generation of a Retrograde Signaling Complex from Sentinel mRNAs in Axons


April 2018:

» #1 Stabilizing the Retromer Complex in a Human Stem Cell Model of Alzheimer's Disease Reduces TAU Phosphorylation Independently of Amyloid Precursor Protein

» #2 Medical Retirement from Sport after Concussions: A Practical Guide for a Difficult Discussion


March 2018:

» #1 Cross Domain Self-Monitoring in Anosognosia for Memory Loss in Alzheimer's Disease

» #2 White Matter Changes in Alzheimer's Disease: A Focus on Myelin and Oligodendrocytes


February 2018:

» #1 ZCCHC17 is a Master Regulator of Synaptic Gene Expression in Alzheimer's Disease

» #2 Imaging Translocator Protein as a Biomarker of Neuroinflammation in Dementia

» #3 A Transcriptomic Atlas of Aged Human Microglia


January 2018:

» #1 Neuronal Lysosomal Dysfunction Releases Exosomes Harboring APP C-terminal Fragments and Unique Lipid Signatures

» #2 An Inflammation-Related Nutrient Pattern is Associated with Both Brain and Cognitive Measures in a Multiethnic Elderly Population




Alzheimer's Association International Conference (AAIC 2019)

Earlier this month, thousands of dementia researchers, clinicians, and related healthcare professionals from around the globe gathered in Los Angeles, CA for the annual Alzheimer's Association International Conference (AAIC 2019). Each year, Taub faculty members travel to this event to share their groundbreaking research and network with others in the field. Below are some highlights of presentations given by Taub faculty at this year's conference:

Dr. Philip L. De Jager detailed latest efforts by his team in the Center for Translational and Computational Neuroimmunology to identify "omic" changes related to AD pathology in the frontal cortex, and how these approaches are now being applied to other brain regions and peripheral monocytes in which the relationship to neurovascular disease may be more pronounced.

Dr. Yian Gu presented results from a recent study on the protective role of physical activity (PA) on Alzheimerā€™s disease risk, which suggest that both young and old individuals can reduce their likelihood of developing AD via physical activity, including frequent light-intensity activities.

Dr. William (Chuck) Kreisl presented research in which the 18F-MK-6240 PET radioligand appeared to identify tau pathology in preclinical Alzheimerā€™s disease and primary age related tauopathy, and to distinguish cases of hippocampal-sparing AD and an amyloid pathophysiological process with a concomitant non-tau copathology (A+T-N+) from typical AD.

In a focused topic session on the importance of the proposed nomenclature for Limbic-Predominant Age-related TDP Encephalopathy, Dr. Jennifer Manly participated in a panel discussion on "LATE into the World of Alzheimerā€™s Dementia? Nomenclature to Advance Science amidst Multiple Stakeholders."


Richard Mayeux, MD, MSc

Taub co-director Dr. Richard Mayeux (pictured right) detailed his teamā€™s work on the first investigation to establish a genome-wide statistically significant association between multiple, extremely rare, loss-of-function variants in SORL1 and Alzheimer's disease, in a large whole-exome study of unrelated cases and controls.

Latest research presented by Dr. Christiane Reitz confirmed previously reported risk loci and identified several novel candidate loci for AD in African Americans. Her findings also highlighted Wnt signaling as a potential causative pathway, and substantiated a potential involvement of KCNMB2 at 3q26.32, which recently emerged as the top locus associated with hippocampal sclerosis pathology in a genome-wide association study using brain neuropathologic data.

Expanding on his previous work on retromer, a protein complex central to endosomal trafficking and linked to Alzheimerā€™s disease, Dr. Scott Small presented results from his latest study, which show that retromer/endosomal dysfunction in mice can recapitulate neuronal and glia defects observed in AD.

Dr. Yaakov Stern chaired the Alzheimer's Association ISTAART Professional Interest Area (PIA) on "Reserve, Resilience, and Protective Factors in Alzheimer's disease," which he first initiated four years ago. This will be Dr. Sternā€™s last year chairing this scientific session, though he will remain in a leadership role as Immediate Past Chair at the AAIC 2020. At the meeting, Dr. Stern also delivered a business talk about the 1st Workshop on Research Definitions for Reserve and Resilience in Cognitive Aging and Dementia that he will be chairing this September.

Dr. Sarah Tom presented results of her recent study examining the contribution of life course risk factors to dementia incidence trends, which found that, among women born in the first half of the 20th century, dementia incidence was lowest for those born during the Great Depression. These relationships were not completely mediated by early life socioeconomic status or education.



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