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Full-Text Articles in Medicine and Health Sciences
Kl-Vs Heterozygosity Is Associated With Lower Amyloid-Dependent Tau Accumulation And Memory Impairment In Alzheimer’S Disease, Julia Neitzel, Nicolai Franzmeier, Anna Rubinski, Martin Dichgans, Matthias Brendel, Michael Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Enchi Liu, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles Decarli, Bret Borowski
Kl-Vs Heterozygosity Is Associated With Lower Amyloid-Dependent Tau Accumulation And Memory Impairment In Alzheimer’S Disease, Julia Neitzel, Nicolai Franzmeier, Anna Rubinski, Martin Dichgans, Matthias Brendel, Michael Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Enchi Liu, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles Decarli, Bret Borowski
Medical Biophysics Publications
Klotho-VS heterozygosity (KL-VShet) is associated with reduced risk of Alzheimer’s disease (AD). However, whether KL-VShet is associated with lower levels of pathologic tau, i.e., the key AD pathology driving neurodegeneration and cognitive decline, is unknown. Here, we assessed the interaction between KL-VShet and levels of beta-amyloid, a key driver of tau pathology, on the levels of PET-assessed neurofibrillary tau in 551 controls and patients across the AD continuum. KL-VShet showed lower cross-sectional and longitudinal increase in tau-PET per unit increase in amyloid-PET when compared to that of non-carriers. This association of KL-VShet on tau-PET was stronger in Klotho mRNA-expressing brain …
Higher Csf Strem2 Attenuates Apoe4-Related Risk For Cognitive Decline And Neurodegeneration, Nicolai Franzmeier, M. Suárez-Calvet, Lukas Frontzkowski, Annah Moore, Timothy J. Hohman, Estrella Morenas-Rodriguez, Brigitte Nuscher, Leslie Shaw, John Q. Trojanowski, Martin Dichgans, Gernot Kleinberger, Christian Haass, Michael Ewers, Michael Weiner, Paul Aisen, Gerald Novak, Robert C. Green, Tom Montine, Ronald Petersen, Anthony Gamst, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Laurel Beckett, Danielle Harvey, John Kornak, Clifford R. Jack, Anders Dale, Matthew Bernstein, Joel Felmlee
Higher Csf Strem2 Attenuates Apoe4-Related Risk For Cognitive Decline And Neurodegeneration, Nicolai Franzmeier, M. Suárez-Calvet, Lukas Frontzkowski, Annah Moore, Timothy J. Hohman, Estrella Morenas-Rodriguez, Brigitte Nuscher, Leslie Shaw, John Q. Trojanowski, Martin Dichgans, Gernot Kleinberger, Christian Haass, Michael Ewers, Michael Weiner, Paul Aisen, Gerald Novak, Robert C. Green, Tom Montine, Ronald Petersen, Anthony Gamst, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Laurel Beckett, Danielle Harvey, John Kornak, Clifford R. Jack, Anders Dale, Matthew Bernstein, Joel Felmlee
Medical Biophysics Publications
Background: The Apolipoprotein E ϵ4 allele (i.e. ApoE4) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). TREM2 (i.e. Triggering receptor expressed on myeloid cells 2) is a microglial transmembrane protein brain that plays a central role in microglia activation in response to AD brain pathologies. Whether higher TREM2-related microglia activity modulates the risk to develop clinical AD is an open question. Thus, the aim of the current study was to assess whether higher sTREM2 attenuates the effects of ApoE4-effects on future cognitive decline and neurodegeneration. Methods: We included 708 subjects ranging from cognitively normal (CN, n = …
Basal Forebrain Volume Reliably Predicts The Cortical Spread Of Alzheimer's Degeneration, Sara Fernández-Cabello, Martin Kronbichler, Koene R.A. Van Dijk, James A. Goodman, R. Nathan Spreng, Taylor W. Schmitz
Basal Forebrain Volume Reliably Predicts The Cortical Spread Of Alzheimer's Degeneration, Sara Fernández-Cabello, Martin Kronbichler, Koene R.A. Van Dijk, James A. Goodman, R. Nathan Spreng, Taylor W. Schmitz
Brain and Mind Institute Researchers' Publications
© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. Alzheimer's disease neurodegeneration is thought to spread across anatomically and functionally connected brain regions. However, the precise sequence of spread remains ambiguous. The prevailing model used to guide in vivo human neuroimaging and non-human animal research assumes that Alzheimer's degeneration starts in the entorhinal cortices, before spreading to the temporoparietal cortex. Challenging this model, we previously provided evidence that in vivo markers of neurodegeneration within the nucleus basalis of Meynert (NbM), a subregion of the basal forebrain heavily populated by cortically projecting cholinergic neurons, …
Mri Investigations Of Metabolic And Structural Brain Changes In Alzheimer’S Disease And Vitamin D Deprivation, Dickson Wong
Mri Investigations Of Metabolic And Structural Brain Changes In Alzheimer’S Disease And Vitamin D Deprivation, Dickson Wong
Electronic Thesis and Dissertation Repository
Alzheimer's disease (AD) is a neurodegenerative disorder of the brain that presents as progressive impairment across several cognitive domains. The biological mechanisms underlying the development of AD remain unclear, with amyloid-beta plaques, neurofibrillary tangles, calcium dysregulation, and oxidative stress all contributing to neurodegeneration in AD. Vitamin D (VitD) deficiency, a common condition in the elderly, may modulate these mechanisms and complicate the AD process. Due to this complicated pathogenesis, the diagnosis of AD requires subjective clinical judgement, staging of AD is challenging, and it remains difficult to predict when and who will progress to AD. The purpose of this thesis …
Can Self-Efficacy Training Improve Memory And Functional Activation In Older Adults With Mild Cognitive Impairment? A Proof-Of-Concept Intervention Study, Brainscan, Western University, Lindsay Nagamatsu, Derek Mitchell, Paul Minda, Amer Burhan, Becky Horst
Can Self-Efficacy Training Improve Memory And Functional Activation In Older Adults With Mild Cognitive Impairment? A Proof-Of-Concept Intervention Study, Brainscan, Western University, Lindsay Nagamatsu, Derek Mitchell, Paul Minda, Amer Burhan, Becky Horst
Project Summaries
The goal of this study is to examine the changes in brain activity after a memory self-efficacy training program to better understand the mechanisms of memory self-efficacy. We will conduct a proof-of-concept six-week memory self-efficacy intervention in older adults with MCI, in order to demonstrate that self-efficacy impacts brain function. This will allow us to determine whether self-efficacy interventions may be a potential strategy for combating AD in the future.
Longitudinal Alzheimer's Degeneration Reflects The Spatial Topography Of Cholinergic Basal Forebrain Projections, Taylor W. Schmitz, Marieke Mur, Meghmik Aghourian, Marc Andre Bedard, R. Nathan Spreng
Longitudinal Alzheimer's Degeneration Reflects The Spatial Topography Of Cholinergic Basal Forebrain Projections, Taylor W. Schmitz, Marieke Mur, Meghmik Aghourian, Marc Andre Bedard, R. Nathan Spreng
Brain and Mind Institute Researchers' Publications
© 2018 The Author(s) The cholinergic neurons of the basal forebrain (BF) provide virtually all of the brain's cortical and amygdalar cholinergic input. They are particularly vulnerable to neuropathology in early Alzheimer's disease (AD) and may trigger the emergence of neuropathology in their cortico-amygdalar projection system through cholinergic denervation and trans-synaptic spreading of misfolded proteins. We examined whether longitudinal degeneration within the BF can explain longitudinal cortico-amygdalar degeneration in older human adults with abnormal cerebrospinal fluid biomarkers of AD neuropathology. We focused on two BF subregions, which are known to innervate cortico-amygdalar regions via two distinct macroscopic cholinergic projections. To …
Genetic Manipulation Of Lactate Metabolism To Regulate Memory And Alzheimer's Disease Pathogenesis, Brainscan , Western University, Robert Cumming, Robert Bartha, Tim Scholl
Genetic Manipulation Of Lactate Metabolism To Regulate Memory And Alzheimer's Disease Pathogenesis, Brainscan , Western University, Robert Cumming, Robert Bartha, Tim Scholl
Project Summaries
Our project will attempt to determine the relative importance of astrocyte or neuronal directed lactate generation on memory by modifying mouse models to either suppress or overexpress the lactate producing enzyme in either cell type. Using these newly created transgenic mouse models, we aim to understand the processes of production and utilization of lactate and its effect on memory and cognition in health and in AD across the lifespan. The outcome of our study may lead to entirely new clinical approaches to treating cognitive and neurodegenerative disorders via drugs which alter lactate metabolism.
Pet And Mri Measurements Of Neuroinflammation And Brain Plasticity After A Stroke, Brainscan , Western University, Jonathan Thiessen, Shawn Whitehead, Justin Hicks, Matthew Fox
Pet And Mri Measurements Of Neuroinflammation And Brain Plasticity After A Stroke, Brainscan , Western University, Jonathan Thiessen, Shawn Whitehead, Justin Hicks, Matthew Fox
Project Summaries
We are going to assess brain structure and function using magnetic resonance imaging (MRI) and positron emission tomography (PET) to study white matter inflammation and the density of synapses over time, alongside a behavioural assessment of motor and executive function. This kind of comprehensive assessment, especially using PET to measure synaptic density, has not been done before.
Integrating Behavioural, Imaging And Transcriptional Profiling To Discover The Impact Of Midlife Stress In Alzheimer's Disease, Brainscan , Western University, Tim Bussey, Flavio Beraldo, Chakravarty Maller, Rosemary Bagot, Sylvain Williams, Claudia Kleinman
Integrating Behavioural, Imaging And Transcriptional Profiling To Discover The Impact Of Midlife Stress In Alzheimer's Disease, Brainscan , Western University, Tim Bussey, Flavio Beraldo, Chakravarty Maller, Rosemary Bagot, Sylvain Williams, Claudia Kleinman
Project Summaries
We will be integrating this cognitive assessment with imaging of brain structure and function to understand the mechanisms by which a risk factor, in this case modifiable life stress, influences Alzheimer's disease-related decline. The resultant data will be integrated and disseminated using a new open-access neuroinformatics platform developed at Western (MouseBytes.ca), which will become a unique resource for open science investigations and set the standard for sharing of behavioural data across the world.
Structural Mri Discriminates Individuals With Mild Cognitive Impairment From Age-Matched Controls: A Combined Neuropsychological And Voxel Based Morphometry Study, Mehul A. Trivedi, Allison K. Wichmann, Britta M. Torgerson, Michael A. Ward, Taylor W. Schmitz, Michele L. Ries, Rebecca L. Koscik, Sanjay Asthana, Sterling C. Johnson
Structural Mri Discriminates Individuals With Mild Cognitive Impairment From Age-Matched Controls: A Combined Neuropsychological And Voxel Based Morphometry Study, Mehul A. Trivedi, Allison K. Wichmann, Britta M. Torgerson, Michael A. Ward, Taylor W. Schmitz, Michele L. Ries, Rebecca L. Koscik, Sanjay Asthana, Sterling C. Johnson
Brain and Mind Institute Researchers' Publications
Background: Several previous studies have reported that amnestic mild cognitive impairment (aMCI), a significant risk factor for Alzheimer's disease (AD), is associated with greater atrophy in the medial temporal lobe (MTL) and posterior cingulate gyrus (PCG). Method: In the present study, we examined the cross-sectional accuracy (i.e., the sensitivity and specificity) of voxel-based morphometry (VBM) in discriminating individuals with MCI (n = 15) from healthy age-matched controls (n = 15). In addition, we also sought to determine whether baseline GM volume predicted aMCI patients that converted to AD from those that did not approximately 2 years after the baseline visit. …