Medicine and Health Sciences Commons^™

Cerebral Amyloid Angiopathy In Down Syndrome And Sporadic And Autosomal-Dominant Alzheimer's Disease, María Carmona-Iragui, Mircea Balasa, Bessy Benejam, Daniel Alcolea, Susana Fernández, Laura Videla, Isabel Sala, María Belén Sánchez-Saudinós, Estrella Morenas-Rodriguez, Roser Ribosa-Nogué, Ignacio Illán-Gala, Sofía Gonzalez-Ortiz, Jordi Clarimón, Frederick A. Schmitt, David K. Powell, Beatriz Bosch, Albert Lladó, Michael S. Rafii, Elizabeth Head, José Luis Molinuevo, Rafael Blesa, Sebastián Videla, Alberto Lleó, Raquel Sánchez-Valle, Juan Fortea

Sanders-Brown Center on Aging Faculty Publications

Introduction—We aimed to investigate if cerebral amyloid angiopathy (CAA) is more frequent in genetically determined than in sporadic early-onset forms of Alzheimer's disease (AD) (early-onset AD [EOAD]).

Methods—Neuroimaging features of CAA, APOE, and cerebrospinal fluid-Aβ40 levels were studied in subjects with Down syndrome (DS, n = 117), autosomal-dominant AD (ADAD, n = 29), sporadic EOAD (n = 42), and healthy controls (n = 68).

Results—CAA was present in 31%, 38%, and 12% of cognitively impaired DS, symptomatic ADAD, and sporadic EOAD subjects and in 13% and 4% of cognitively unimpaired DS individuals and healthy controls, respectively. …

Vocabulary Learning Benefits From Rem After Slow-Wave Sleep., Laura J Batterink, Carmen E Westerberg, Ken A Paller

Brain and Mind Institute Researchers' Publications

Memory reactivation during slow-wave sleep (SWS) influences the consolidation of recently acquired knowledge. This reactivation occurs spontaneously during sleep but can also be triggered by presenting learning-related cues, a technique known as targeted memory reactivation (TMR). Here we examined whether TMR can improve vocabulary learning. Participants learned the meanings of 60 novel words. Auditory cues for half the words were subsequently presented during SWS in an afternoon nap. Memory performance for cued versus uncued words did not differ at the group level but was systematically influenced by REM sleep duration. Participants who obtained relatively greater amounts of REM showed a …

Rabies Screen Reveals Gpe Control Of Cocaine-Triggered Plasticity., Kevin T. Beier, Christina K. Kim, Paul Hoerbelt, Lin Wai Hung, Boris D. Heifets, Katherine E. Deloach, Timothy J. Mosca, Sophie Neuner, Karl Deisseroth, Liqun Luo, Robert C. Malenka

Department of Neuroscience Faculty Papers

Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse. We demonstrated that cocaine increased GPe neuron activity, which accounted for the …

Calcineurin Dysregulation Underlies Spinal Cord Injury-Induced K(+) Channel Dysfunction In Drg Neurons., Benjamin M. Zemel, Tanziyah Muqeem, Eric V. Brown, Miguel Goulão, Mark W Urban, Stephen R. Tymanskyj, Angelo C. Lepore, Manuel Covarrubias

Department of Neuroscience Faculty Papers

Dysfunction of the fast-inactivating Kv3.4 potassium current in dorsal root ganglion (DRG) neurons contributes to the hyperexcitability associated with persistent pain induced by spinal cord injury (SCI). However, the underlying mechanism is not known. In light of our previous work demonstrating modulation of the Kv3.4 channel by phosphorylation, we investigated the role of the phosphatase calcineurin (CaN) using electrophysiological, molecular, and imaging approaches in adult female Sprague Dawley rats. Pharmacological inhibition of CaN in small-diameter DRG neurons slowed repolarization of the somatic action potential (AP) and attenuated the Kv3.4 current. Attenuated Kv3.4 currents also exhibited slowed inactivation. We observed similar …

Rapid Statistical Learning Supporting Word Extraction From Continuous Speech., Laura J Batterink

Brain and Mind Institute Researchers' Publications

The identification of words in continuous speech, known as speech segmentation, is a critical early step in language acquisition. This process is partially supported by statistical learning, the ability to extract patterns from the environment. Given that speech segmentation represents a potential bottleneck for language acquisition, patterns in speech may be extracted very rapidly, without extensive exposure. This hypothesis was examined by exposing participants to continuous speech streams composed of novel repeating nonsense words. Learning was measured on-line using a reaction time task. After merely one exposure to an embedded novel word, learners demonstrated significant learning effects, as revealed by …

Risk Of Incident Clinical Diagnosis Of Alzheimer's Disease-Type Dementia Attributable To Pathology-Confirmed Vascular Disease, Hiroko H. Dodge, Jian Zhu, Randy Woltjer, Peter T. Nelson, David A. Bennett, Nigel J. Cairns, David W. Fardo, Jeffrey A. Kaye, Deniz-Erten Lyons, Nora Mattek, Julie A. Schneider, Lisa C. Silbert, Chengjie Xiong, Lei Yu, Frederick A. Schmitt, Richard J. Kryscio, Erin L. Abner, Smart Data Consortium

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: The presence of cerebrovascular pathology may increase the risk of clinical diagnosis of Alzheimer's disease (AD).

METHODS: We examined excess risk of incident clinical diagnosis of AD (probable and possible AD) posed by the presence of lacunes and large infarcts beyond AD pathology using data from the Statistical Modeling of Aging and Risk of Transition study, a consortium of longitudinal cohort studies with more than 2000 autopsies. We created six mutually exclusive pathology patterns combining three levels of AD pathology (low, moderate, or high AD pathology) and two levels of vascular pathology (without lacunes and large infarcts or with …

Online Neural Monitoring Of Statistical Learning., Laura J Batterink, Ken A Paller

Brain and Mind Institute Researchers' Publications

The extraction of patterns in the environment plays a critical role in many types of human learning, from motor skills to language acquisition. This process is known as statistical learning. Here we propose that statistical learning has two dissociable components: (1) perceptual binding of individual stimulus units into integrated composites and (2) storing those integrated representations for later use. Statistical learning is typically assessed using post-learning tasks, such that the two components are conflated. Our goal was to characterize the online perceptual component of statistical learning. Participants were exposed to a structured stream of repeating trisyllabic nonsense words and a …

Sleep-Based Memory Processing Facilitates Grammatical Generalization: Evidence From Targeted Memory Reactivation., Laura J Batterink, Ken A Paller

Brain and Mind Institute Researchers' Publications

Generalization-the ability to abstract regularities from specific examples and apply them to novel instances-is an essential component of language acquisition. Generalization not only depends on exposure to input during wake, but may also improve offline during sleep. Here we examined whether targeted memory reactivation during sleep can influence grammatical generalization. Participants gradually acquired the grammatical rules of an artificial language through an interactive learning procedure. Then, phrases from the language (experimental group) or stimuli from an unrelated task (control group) were covertly presented during an afternoon nap. Compared to control participants, participants re-exposed to the language during sleep showed larger …

Outcomes After Diagnosis Of Mild Cognitive Impairment In A Large Autopsy Series, Erin L. Abner, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Daniela C. Moga, Eseosa T. Ighodaro, Gregory A. Jicha, Lei Yu, Hiroko H. Dodge, Chengjie Xiong, Randall L. Woltjer, Julie A. Schneider, Nigel J. Cairns, David A. Bennett, Peter T. Nelson

Epidemiology and Environmental Health Faculty Publications

OBJECTIVE: To determine clinical and neuropathological outcomes following a clinical diagnosis of mild cognitive impairment (MCI).

METHODS: Data were drawn from a large autopsy series (N = 1,337) of individuals followed longitudinally from normal or MCI status to death, derived from 4 Alzheimer Disease (AD) Centers in the United States.

RESULTS: Mean follow‐up was 7.9 years. Of the 874 individuals ever diagnosed with MCI, final clinical diagnoses were varied: 39.2% died with an MCI diagnosis, 46.8% with a dementia diagnosis, and 13.9% with a diagnosis of intact cognition. The latter group had pathological features resembling those with a final clinical …

Csf Protein Changes Associated With Hippocampal Sclerosis Risk Gene Variants Highlight Impact Of Grn/Pgrn, David W. Fardo, Yuriko Katsumata, John S. K. Kauwe, Yuetiva Deming, Oscar Harari, Carlos Cruchaga, Alzheimer’S Disease Neuroimaging Initiative, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Objective—Hippocampal sclerosis of aging (HS-Aging) is a common cause of dementia in older adults. We tested the variability in cerebrospinal fluid (CSF) proteins associated with previously identified HS-Aging risk single nucleotide polymorphisms (SNPs).

Methods—Alzheimer’s Disease Neuroimaging Initiative cohort (ADNI; n=237) data, combining both multiplexed proteomics CSF and genotype data, were used to assess the association between CSF analytes and risk SNPs in four genes (SNPs): GRN (rs5848), TMEM106B (rs1990622), ABCC9 (rs704180), and KCNMB2 (rs9637454). For controls, non-HS-Aging SNPs in APOE (rs429358/rs7412) and MAPT (rs8070723) were also analyzed against Aβ1-42 and total tau CSF analytes.

Results—The GRN risk …

Quantitative Assessment Of White Matter Injury In Preterm Neonates: Association With Outcomes., Ting Guo, Emma G Duerden, Elysia Adams, Vann Chau, Helen M Branson, M Mallar Chakravarty, Kenneth J Poskitt, Anne Synnes, Ruth E Grunau, Steven P Miller

Brain and Mind Institute Researchers' Publications

OBJECTIVE: To quantitatively assess white matter injury (WMI) volume and location in very preterm neonates, and to examine the association of lesion volume and location with 18-month neurodevelopmental outcomes.

METHODS: Volume and location of WMI was quantified on MRI in 216 neonates (median gestational age 27.9 weeks) who had motor, cognitive, and language assessments at 18 months corrected age (CA). Neonates were scanned at 32.1 postmenstrual weeks (median) and 68 (31.5%) had WMI; of 66 survivors, 58 (87.9%) had MRI and 18-month outcomes. WMI was manually segmented and transformed into a common image space, accounting for intersubject anatomical variability. Probability …

Map7 Regulates Axon Collateral Branch Development In Dorsal Root Ganglion Neurons., Stephen R Tymanskyj, Benjamin Yang, Aditi Falnikar, Angelo C Lepore, Le Ma

Department of Neuroscience Faculty Papers

Collateral branches from axons are key components of functional neural circuits that allow neurons to connect with multiple synaptic targets. Like axon growth and guidance, formation of collateral branches depends on the regulation of microtubules, but how such regulation is coordinated to ensure proper circuit development is not known. Based on microarray analysis, we have identified a role for microtubule-associated protein 7 (MAP7) during collateral branch development of dorsal root ganglion (DRG) sensory neurons. We show that MAP7 is expressed at the onset of collateral branch formation. Perturbation of its expression by overexpression or shRNA knockdown alters axon branching in …