Nervous System Diseases Commons^™

Partial Purification Of Alzheimer’S Amyloid-𝛽 Specific Antibody Using Ammonium Sulfate, Noor Yousaf

Undergraduate Research Symposium

Alzheimer's disease (AD) is the most common neurodegenerative disease. The trigger for AD is the accumulation of amyloid-beta protein (Aβ) as senile plaques in the brain. Prior to forming the fiber-like structures found in the plaques, Aβ undergoes an oligomerization process that produces intermediate structures called protofibrils. Substantial data from the Nichols laboratory demonstrated that soluble Aβ protofibrils were highly inflammatory compared to other forms of Aβ. Based on these findings, a serum polyclonal antibody, named Antibody St. Louis or AbSL, was developed to target Aβ protofibrils. A significant challenge with serum antibodies is the presence of many other biological …

In Vivo Examination Of Peripheral Drivers Of Alzheimer’S Disease, Celso Catumbela

Dissertations & Theses (Open Access)

Alzheimer’s disease (AD) is the leading cause of dementia worldwide, and predominantly affects elderly populations. This disease is well known for its effects on the brain, but a wealth of clinical reports show that dementia can also modify, or be modified by, various peripheral and systemic processes. Yet, the pathological contribution of peripheral comorbidities to AD remains to be fully understood. In an attempt to address some knowledge gaps, we characterized the cerebral and peripheral pathology in mice with history of either liver injury or sepsis. In the former subjects, we found that even in the absence of genetic risk …

Cognitive Reserve, Cortisol, And Alzheimer's Disease Biomarkers: A Memory Clinic Study, Manasa Yerramalla, Alexander Darin-Mattsson, Chinedu Momoh, Jasper Holleman, Ingemar Kåreholt, Malin Aspö, Göran Hagman, Miia Kivipelto, Alina Solomon, Anna Marseglia

Brain and Mind Institute

INTRODUCTION Cognitive reserve might mitigate the risk of Alzheimer's dementia among memory clinic patients. No study has examined the potential modifying role of stress on this relation.

METHODS We examined cross-sectional associations of the cognitive reserve index (CRI; education, occupational complexity, physical and leisure activities, and social health) with cognitive performance and AD-related biomarkers among 113 memory clinic patients. The longitudinal association between CRI and cognition over a 3-year follow-up was assessed. We examined whether associations were influenced by perceived stress and five measures of diurnal salivary cortisol.

RESULTS Higher CRI scores were associated with better cognition. Adjusting for cortisol …

Modulation Of Hippocampal Protein Expression By A Brain Penetrant Biologic Tnf-Α Inhibitor In The 3xtg Alzheimer’S Disease Mice, Nataraj Jagadeesan, G. Chuli Roules, Devaraj V. Chandrashekar, Joshua Yang, Sanjana Kolluru, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background

Biologic TNF-α inhibitors (bTNFIs) can block cerebral TNF-α in Alzheimer’s disease (AD) if these macromolecules can cross the blood–brain barrier (BBB). Thus, a model bTNFI, the extracellular domain of type II TNF-α receptor (TNFR), which can bind to and sequester TNF-α, was fused with a mouse transferrin receptor antibody (TfRMAb) to enable brain delivery via BBB TfR-mediated transcytosis. Previously, we found TfRMAb-TNFR to be protective in a mouse model of amyloidosis (APP/PS1) and tauopathy (PS19), and herein we investigated its effects in mice that combine both amyloidosis and tauopathy (3xTg-AD).

Methods

Eight-month-old female 3xTg-AD mice were injected intraperitoneally with …

Deciphering The Role Of Hsp110 Chaperones In Diseases Of Protein Misfolding, Unekwu M. Yakubu

Dissertations & Theses (Open Access)

Molecular chaperones maintain protein homeostasis (proteostasis) by ensuring the proper folding of polypeptides. Loss of proteostasis has been linked to the onset of numerous neurodegenerative disorders including Alzheimer’s, Parkinson’s, and Huntington’s disease. Hsp110 is a member of the Hsp70 class of molecular chaperones and acts as a nucleotide exchange factor (NEF) for Hsp70, the preeminent Hsp70-family protein folding chaperone. Hsp110 promotes rapid cycling of ADP for ATP, allowing Hsp70 to properly fold nascent or unfolded polypeptides in iterative cycles. In addition to its NEF activity, Hsp110 possesses an Hsp70-like substrate binding domain (SBD) whose biological roles are undefined. Previous work …

Core Alzheimer’S Disease Cerebrospinal Fluid Biomarker Assays Are Not Affected By Aspiration Or Gravity Drip Extraction Methods, James D. Doecke, Cindy Francois, Christopher J. Fowler, Erik Stoops, Pierrick Bourgeat, Stephanie R. Rainey-Smith, Qiao-Xin Li, Colin L. Masters, Ralph N. Martins, Victor L. Villemagne, Steven J. Collins, Hugo Marcel Vanderstichele

Research outputs 2014 to 2021

Background: CSF biomarkers are well-established for routine clinical use, yet a paucity of comparative assessment exists regarding CSF extraction methods during lumbar puncture. Here, we compare in detail biomarker profiles in CSF extracted using either gravity drip or aspiration. Methods: Biomarkers for β-amyloidopathy (Aβ1–42, Aβ1–40), tauopathy (total tau), or synapse pathology (BACE1, Neurogranin Trunc-p75, α-synuclein) were assessed between gravity or aspiration extraction methods in a sub-population of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study (cognitively normal, N = 36; mild cognitive impairment, N = 8; Alzheimer’s disease, N = 6). Results: High biomarker concordance between extraction methods was seen …

The Effect Of The Interaction Of Exercise Training And Isolation On The Serotonergic System Of App/Ps1 Mice, Bailey J. Dansby

MSU Graduate Theses

Alzheimer’s disease (AD) is a complex neurodegenerative disease that is characterized by the deposition of amyloid beta (Ab) peptides and, consecutively, by a loss of memory and cognitive functions. The amyloid cascade hypothesis suggests that Ab deposition is the main pathogenic of AD. There is evidence that both changes in production and clearance of Ab may be involved in AD pathology. Past studies have shown that exercise training leads to an upregulation in proteins directly involved with Ab clearance. Chronic stress is thought to exacerbate AD pathology by increasing production of Ab. Studies have also demonstrated a link between serotonin …

The Association Between Herpes Simplex Virus Type 1 Reactivation And Alzheimer’S Disease, Andrew Allee

BIO 410 Spring 2019 Research Papers

This review will focus on the interaction of herpes simplex virus type 1 (HSV-1) and its causative role in pathogenesis of Alzheimer’s disease (AD) noting specifically, the epidemiological relevance of addressing this problem, as well as the molecular pathways associated. HSV-1 reactivation tends to be one of the primary causative events that is responsible for many of the pathologies associated with AD, such as: amyloid beta (Aβ) accumulation caused by malfunctioning cleavage of amyloid precursor protein (APP) as well as tau hyperphosphorylation. HSV-1 reactivation is a primary causative event in downstream dysfunction and is also shown to be directed by …

Oxidative Stress And Proteomic Studies Of Mammalian Models Of Age-Related Metabolic Dysfunction In Neurodegenerative Disorders, Aaron M. Swomley

Theses and Dissertations--Chemistry

Expression proteomics is the field of science wherein proteins that make up the cellular proteome are identified both by name and by fold-change. Depending on the application of proteomics, this change in level could be due to internal cellular stressors or introduction of xenobiotics. Global oxidative stress measures use immunohistochemistry to determine the relative level of oxidative stress of macromolecules within the cell. In this dissertation, both global oxidative stress measures and expression proteomics were used in a variety of mammalian models in order to determine the effects of protein upregulation, intranasal insulin administration, and resveratrol supplementation on the cellular …

Local And Distributed Pib Accumulation Associated With Development Of Preclinical Alzheimer's Disease, Matthew R. Brier, John E. Mccarthy, Tammie L.S. Benzinger, Ari Stern, Yi Su, Karl A. Friedrichsen, John C. Morris, Beau M. Ances, Andrei G. Vlassenko

Mathematics Faculty Publications

Amyloid-beta plaques are a hallmark of Alzheimer's disease (AD) that can be assessed by amyloid imaging (e.g., Pittsburgh B compound [PiB]) and summarized as a scalar value. Summary values may have clinical utility but are an average over many regions of interest, potentially obscuring important topography. This study investigates the longitudinal evolution of amyloid topographies in cognitively normal older adults who had normal (N = 131) or abnormal (N = 26) PiB scans at baseline. At 3 years follow-up, 16 participants with a previously normal PiB scan had conversion to PiB scans consistent with preclinical AD. We investigated the multivariate …

Detection Of Bacterial Antigens And Alzheimer's Disease-Like Pathology In The Central Nervous System Of Balb/C Mice Following Intranasal Infection With A Laboratory Isolate Of Chlamydia Pneumoniae, C. Scott Little Phd, Timothy A. Joyce, Christine Hammond, Hazem Matta, David Cahn, Denah Appelt, Brian J. Balin Phd

PCOM Scholarly Works

Pathology consistent with that observed in Alzheimer’s disease (AD) has previously been documented following intranasal infection of normal wild-type mice with Chlamydia pneumoniae (Cpn) isolated from an AD brain (96-41). In the current study, BALB/c mice were intranasally infected with a laboratory strain of Cpn, AR-39, and brain and olfactory bulbs were obtained at 1-4 months post-infection (pi). Immunohistochemistry for amyloid beta or Cpn antigens was performed on sections from brains of infected or mock-infected mice. Chlamydia-specific immunolabeling was identified in olfactory bulb tissues and in cerebrum of AR-39 infected mice. The Cpn specific labeling was most prominent at 1 …