Medicine and Health Sciences Commons^™

Investigating The Relationship Between Peripheral Microvascular And Cerebral Vascular Vasodilator Function In College-Aged Individuals, John Kolade, John Akins, Alison Ortiz, Robert Brothers

International Journal of Exercise Science: Conference Proceedings

Peripheral vascular dysfunction is predictive of numerous conditions including hypertension, type II diabetes, and coronary heart disease. Likewise, impaired cerebral vascular function is linked to neurocognitive conditions including Alzheimer’s disease and related dementias, cognitive dysfunction, and stroke. Previous research has reported no relationship between peripheral and extracranial macrovascular function within individuals. However, to our knowledge, no studies have examined the relationship between peripheral microvascular and cerebral vascular function within individuals. PURPOSE: To test the hypothesis that peripheral microvascular and cerebral vascular function would not be similar within young healthy individuals. METHODS: Data was collected in 59 participants (45 female; …

The Effect Of Ghrelin On Antioxidant Status In The Rat’S Model Of Alzheimer's Disease Induced By Amyloid-Beta, Fatemeh Sarlaki, Zahra Shahsavari, Fatemeh Goshadrou, Faezeh Naseri, Mohammad Keimasi, Majid Sirati-Sabet Dr

BioMedicine

Alzheimer's disease (AD) is a neurodegenerative disorder associated with amyloid-beta (Aβ) plaque formation and oxidative stress in the brain. Ghrelin has been proven to exert antioxidant activity and neuroprotection in different neurological diseases. This study is going on to examine the effect of ghrelin on antioxidant status in the rat’s model of AD induced by Aβ. Cognitive impairment was induced by intra-hippocampal administration of Aβ (10 µg) in Wistar rats and ghrelin (80 μg/kg) was administrated intraperitoneal for ten consecutive days. Behavior was assessed with Morris water maze and passive avoidance tests. Malondialdehyde (MDA) level as a marker of lipid …

Apoe Ε2 Resilience For Alzheimer’S Disease Is Mediated By Plasma Lipid Species: Analysis Of Three Independent Cohort Studies, Tingting Wang, Kevin Huynh, Corey Giles, Natalie A. Mellett, Thy Duong, Anh Nguyen, Wei L. F. Lim, Alex A. T. Smith, Gavriel Olshansky, Gemma Cadby, Joseph Hung, Jennie Hui, John Beilby, Gerald F. Watts, Pratishtha Chatterjee, Ian Martins, Simon Laws, Ashley I. Bush, Christopher C. Rowe, Victor L. Villemagne, David Ames, Colin L. Masters, Kevin Taddei, Vincent Doré, Jürgen Fripp, Matthias Arnold, Gabi Kastenmüller, Kwangsik Nho, Andrew J. Saykin, Rebecca Baillie, Xianlin Han, Ralph N. Martins, Eric K. Moses, Rima Kaddurah-Daouk, Peter J. Meikle

Research outputs 2022 to 2026

Introduction:

The apolipoprotein E (APOE) genotype is the strongest genetic risk factor for late-onset Alzheimer's disease. However, its effect on lipid metabolic pathways, and their mediating effect on disease risk, is poorly understood.

Methods:

We performed lipidomic analysis on three independent cohorts (the Australian Imaging, Biomarkers and Lifestyle [AIBL] flagship study, n = 1087; the Alzheimer's Disease Neuroimaging Initiative [ADNI] 1 study, n = 819; and the Busselton Health Study [BHS], n = 4384), and we defined associations between APOE ε2 and ε4 and 569 plasma/serum lipid species. Mediation analysis defined the proportion of the treatment effect of the APOE …

Transcriptional Profiles In Olfactory Pathway-Associated Brain Regions Of African Green Monkeys: Associations With Age And Alzheimer’S Disease Neuropathology, Jacob D Negrey, Dorothy L Dobbins, Timothy D Howard, Karin E Borgmann-Winter, C G Hahn, Sergey Kalinin, Douglas L Feinstein, Suzanne Craft, Carol A Shively, Thomas C Register

Department of Neuroscience Faculty Papers

Introduction: Olfactory impairment in older individuals is associated with an increased risk of Alzheimer's disease (AD). Characterization of age versus neuropathology-associated changes in the brain olfactory pathway may elucidate processes underlying early AD pathogenesis. Here, we report age versus AD neuropathology-associated differential transcription in four brain regions in the olfactory pathway of 10 female African green monkeys (vervet, Chlorocebus aethiops sabaeus), a well-described model of early AD-like neuropathology.

Methods: Transcriptional profiles were determined by microarray in the olfactory bulb (OB), piriform cortex (PC), temporal lobe white matter (WM), and inferior temporal cortex (ITC). Amyloid beta (Aβ) plaque load in …

Plasma High-Density Lipoprotein Cargo Is Altered In Alzheimer's Disease And Is Associated With Regional Brain Volume, Steve Pedrini, James D. Doecke, Eugene Hone, Penghao Wang, Rohith Thota, Ashley I. Bush, Christopher C. Rowe, Vincent Dore, Victor L. Villemagne, David Ames, Stephanie Rainey-Smith, Giuseppe Verdile, Hamid R. Sohrabi, Manfred R. Raida, Kevin Taddei, Sam Gandy, Colin L. Masters, Pratishtha Chatterjee, Ralph N. Martins, Aibl Research Group

Research outputs 2022 to 2026

Cholesterol levels have been repeatedly linked to Alzheimer's Disease (AD), suggesting that high levels could be detrimental, but this effect is likely attributed to Low-Density Lipoprotein (LDL) cholesterol. On the other hand, High-Density Lipoproteins (HDL) cholesterol levels have been associated with reduced brain amyloidosis and improved cognitive function. However, recent findings have suggested that HDL-functionality, which depends upon the HDL-cargo proteins associated with HDL, rather than HDL levels, appears to be the key factor, suggesting a quality over quantity status. In this report, we have assessed the HDL-cargo (Cholesterol, ApoA-I, ApoA-II, ApoC-I, ApoC-III, ApoD, ApoE, ApoH, ApoJ, CRP, and SAA) …

Understanding The Relationship Between Age-Related Hearing Loss And Alzheimer's Disease: A Narrative Review, Hadeel Y. Tarawneh, Dona M. P. Jayakody, Hamid R. Sohrabi, Ralph N. Martins, Wilhelmina H.A.M. Mulders

Research outputs 2022 to 2026

Evidence suggests that hearing loss (HL), even at mild levels, increases the long-term risk of cognitive decline and incident dementia. Hearing loss is one of the modifiable risk factors for dementia, with approximately 4 million of the 50 million cases of dementia worldwide possibly attributed to untreated HL. This paper describes four possible mechanisms that have been suggested for the relationship between age-related hearing loss (ARHL) and Alzheimer's disease (AD), which is the most common form of dementia. The first mechanism suggests mitochondrial dysfunction and altered signal pathways due to aging as a possible link between ARHL and AD. The …

Adult Day Services In Maine: Benefits, Challenges, And Opportunities, Elizabeth Gattine Jd, Eileen Griffin Jd, Kimberly I. Snow Mhsa, Ba

Disability & Aging

In Maine and nationally, adult day services tend to be underfunded and underutilized compared to other types of long term services and supports (LTSS). In part, investment in adult day services is hampered by a lack of standardized data collection and limited research on issues of accessibility, cost-effectiveness, and the impact of adult day services on the broader health system. Lack of uniformity in state regulatory frameworks for licensing, program design, service delivery, and other administrative requirements further complicates cross-state comparisons. Considering these limitations, a key goal of this report is to provide a more detailed and comprehensive understanding of …

Systemic Perturbations Of The Kynurenine Pathway Precede Progression To Dementia Independently Of Amyloid-Β, Marcela Cespedes, Kelly R. Jacobs, Paul Maruff, Alan Rembach, Christopher J. Fowler, Brett Trounson, Kelly K. Pertile, Rebecca L. Rumble, Stephanie R. Rainey-Smith, Christopher C. Rowe, Victor L. Villemagne, Pierrick Bourgeat, Chai K. Lim, Pratishtha Chatterjee, Ralph N. Martins, Arne Ittner, Colin L. Masters, James D. Doecke, Gilles J. Guillemin, David B. Lovejoy

Research outputs 2022 to 2026

Increasing evidence suggests that kynurenine pathway (KP) dyshomeostasis may promote disease progression in dementia. Studies in Alzheimer's disease (AD) patients confirm KP dyshomeostasis in plasma and cerebrospinal fluid (CSF) which correlates with amyloid-β and tau pathology. Herein, we performed the first comprehensive study assessing baseline levels of KP metabolites in participants enrolling in the Australian Imaging Biomarkers Flagship Study of Aging. Our purpose was to test the hypothesis that changes in KP metabolites may be biomarkers of dementia processes that are largely silent. We used a cross-sectional analytical approach to assess non-progressors (N = 73); cognitively normal (CN) or mild …

Pineal Cyst Apoplexy And Memory Loss: A Novel Complication, Areez Shafqat, Hanin Jaber Algethami, Shameel Shafqat, Syed Shafqat Ul Islam

Medical College Documents

An 8-year-old boy presented to our hospital complaining of a bilateral headache associated with episodes of anterograde amnesia. He had a road traffic accident 3 years ago when a computed tomography (CT) scan revealed traumatic brain injury. In addition, a small pineal cyst (PC) was noted with minor intramural calcifications. A follow-up CT a day later demonstrated increased density in the pineal gland of 60 Hounsfield Units, suggestive of apoplectic changes in the PC. However, the patient was lost to follow-up and presented with memory loss a year and a half later, upon which CT and magnetic resonance imaging revealed …

The Effects Of Physical Function And Genetics On Cognition And Blood Biomarkers In Individuals At-Risk For Alzheimer’S Disease And Related Dementias, Joshua Louis Gills

Graduate Theses and Dissertations

Alzheimer’s disease and related dementia (ADRD) rates are expected to triple by the year 2050. Early detection and specific mitigation efforts are warranted to blunt the alarming rate. Physical function (PF) declines with age, but higher physical function is associated with better cognitive functioning in middle-to- older age individuals. Moreover, greater physical activity (PA) is associated with better global cognition; however, Apoliporotein e4 carriers may not gain the same benefits with exercise. Additionally, plasma phosphorylated tau 217 (p-tau217) has been identified as a novel diagnostic ADRD biomarker which needs further research to examine associations with risk factors. Therefore, the aims …

Palliative Care Screening For Persons Living With Dementia In A Nursing Home, Shanika S. Pruitt

Dissertations

Problem: Dementia is rapidly increasing as the people of the world mature and life expectancy increases. As the world ages and the prevalence of dementia increases, nursing home placement will and is the most sought place for care of this population. Dementia is under recognized as a terminal illness and palliative care is underutilized for nursing home residents with advanced symptoms of dementia.

Methods: This quality improvement (QI) initiative utilized a prospective, descriptive design. The Palliative Care Screening for the Elderly tool was administered to a purposive sample of persons living with dementia residing in the nursing home. Qualitative data …

Making The Case For The Accelerated Withdrawal Of Aducanumab, Peter J. Whitehouse

Faculty Scholarship

U.S. Food and Drug Administration-s (FDA) approval of aducanumab (Aduhelm® in the US) as a treatment for mild cognitive impairment of the Alzheimer type and Alzheimer-s disease has raised such major concerns about efficacy, safety, FDA processes, and regulatory capture that Biogen-s license to market this biologic should be immediately withdrawn. Aducanumab has not demonstrated benefit to patients, failed to meet regulatory guidelines, and is likely to cause both individual and societal harm.

Modulation Of Immune Homeostasis In Neurodegenerative Diseases, Pravin Yeapuri

Theses & Dissertations

Modulating the immune system via. transformation of CD4+ T cell effector to regulatory (Teff to Treg) or promoting microglial clearance of abnormal disease proteins are attractive therapeutic strategies to restore immunological balance in neurodegenerative diseases like Parkinson’s disease (PD) and Alzheimer’s disease (AD). In the past decade, we defined a safe and effective pathway for Treg induction through the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF was developed in PD animal models and early phase I human studies demonstrating proof-of-concept efficacy for ameliorating disease signs and symptoms. Despite the recorded efficacy, the medicine’s short half-life, limited bioavailability, and injection site reactions …

An Investigative Study Into Alzheimer’S Disease (Ad): Development, Pathway And Progression, And Novel Treatment, Aruha Khan

Chancellor’s Honors Program Projects

No abstract provided.

The Impact Of Cognitive Rehabilitation Therapy On Alzheimer's Disease, Kelsey Hall

MSN Capstone Projects

The number of people suffering from Alzheimer’s disease (AD) rises daily. This is a devastating disease for the patients, significant others, and families to have to experience. “Epidemiological data confirm what retirees have observed: about 30-50% of those living to their mid-80’s will have suffered a marked loss of cognitive ability, a harbinger of advanced AD, or will have suffered advanced AD. Further, the tragedy of AD affecting loved partners takes an enormous toll on their healthier partners” (Reid et al., 2017).

The current treatment regimen for Alzheimer’s disease includes medication therapy. Evidence has shown that there are only small …

Alzheimer's And Patient Caregiver Burnout: A Review Of The Literature, Madeline Hekeler

James Madison Undergraduate Research Journal (JMURJ)

The term “silent epidemic” is fitting for Alzheimer’s disease (AD), as its negative impact is widely felt but rarely discussed. Burnout among AD caregivers has become an epidemic of its own as caregivers experience an increase in health risks, stress, and financial burden. This literature review focuses on caregiver burnout and how imperative it is that caregivers are better supported in their role. Researchers have developed instruments to assess and intervene in caregiver burnout that have shown effectiveness among caregivers and their families.Nevertheless, further longitudinal research is warranted regarding more effective interventions, including stress management and social support mechanisms.

The Association Between Alzheimer's Disease-Related Markers And Physical Activity In Cognitively Normal Older Adults, Steve Pedrini, Pratishtha Chatterjee, Akinori Nakamura, Michelle Tegg, Eugene Hone, Stephanie R. Rainey-Smith, Christopher C. Rowe, Vincent Dore, Victor L. Villemagne, David Ames, Naoki Kaneko, Samantha L. Gardener, Kevin Taddei, Binosha Fernando, Ian Martins, Prashant Bharadwaj, Hamid R. Sohrabi, Colin L. Masters, Belinda Brown, Ralph N. Martins, Aibl Research Group

Research outputs 2022 to 2026

Previous studies have indicated that physical activity may be beneficial in reducing the risk for Alzheimer's disease (AD), although the underlying mechanisms are not fully understood. The goal of this study was to evaluate the relationship between habitual physical activity levels and brain amyloid deposition and AD-related blood biomarkers (i.e., measured using a novel high-performance mass spectrometry-based assay), in apolipoprotein E (APOE) ε4 carriers and noncarriers. We evaluated 143 cognitively normal older adults, all of whom had brain amyloid deposition assessed using positron emission tomography and had their physical activity levels measured using the International Physical Activity Questionnaire (IPAQ). We …

Blood Biomarkers For Cognitive Decline And Clinical Progression In A Mexican American Cohort, Mitzi M. Gonzales, Chen-Pin Wang, Meghan I. Short, Danielle M. Parent, Tiffany Kautz, Daniel Maccarthy, Claudia L. Satizabal, David Andrés González, Donald R. Royal, Gladys E. Maestre

School of Medicine Publications and Presentations

Introduction: The clinical translation of biofluid markers for dementia requires validation in diverse cohorts. The study goal was to evaluate if blood biomarkers reflecting diverse pathophysiological processes predict disease progression in Mexican American adults.

Methods: Mexican American adults (n = 745), 50 years of age and older, completed annual assessments over a mean of 4 years. Serum collected at baseline was assayed for total tau, neurofilament light (NFL), ubiquitin carboxyl‐terminal hydrolase LI, glial fibrillary acidic protein (GFAP), soluble cluster of differentiation 14 (sCD14), and chitinase‐3‐like protein 1 (YKL‐40).

Results: Higher GFAP and NFL were associated with global …

A Novel Non‑Selective Atypical Pkc Agonist Could Protect Neuronal Cell Line From A Β ‑Oligomer Induced Toxicity By Suppressing A Β Generation, Dongmei Zou, Qian Li, Wenyang Pan, Peng Chen, Miao Sun, Xiaofeng Bao

Publications and Research

Atypical protein kinase C (aPKCs) serve key functions in embryonic development by regulating apical-basal polarity. Previous studies have shed light on their roles during adulthood, especially in the development of Alzheimer's disease (AD). Although the crystal structure of PKCι has been resolved, an agonist of aPKCs remains to be discovered. In the present study, by using the Discovery Studio program and LibDock methodology, a small molecule library (K66-X4436 KINA Set) of compounds were screened for potential binding to PKCι. Subsequently, the computational docking results were validated using affinity selection-mass spectrometry, before in vitro kinase activity was used to determine the …

Aducanumab, A Novel Anti-Amyloid Monoclonal Antibody, For The Treatment Of Alzheimer’S Disease: A Comprehensive Review, Hannah W. Haddad, Garett W. Malone, Nicholas J. Comardelle, Arielle E. Degueure, Adam M. Kaye, Alan David Kaye

School of Pharmacy Faculty Articles

Alzheimer’s disease (AD) is the most common form of dementia affecting millions of individuals, including family members who often take on the role as caregiver. This debilitating disease reportedly consumes 8% of the total United States healthcare expenditure, with medical and nursing outlays accounting for an estimated $290 billion. Cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists have historically been the most widely used pharmacologic therapies for patients with AD, however, these drugs are not curative. This review discusses the epidemiology, pathophysiology, risk factors, presentation, and current treatment of AD followed by the role of the novel monoclonal antibody, aducanumab, in treatment …

Therapeutic Treatment With The Anti-Inflammatory Drug Candidate Mw151 May Partially Reduce Memory Impairment And Normalizes Hippocampal Metabolic Markers In A Mouse Model Of Comorbid Amyloid And Vascular Pathology, David J. Braun, David K. Powell, Christopher J. Mclouth, Saktimayee M. Roy, D. Martin Watterson, Linda J. Van Eldik

Neuroscience Faculty Publications

Alzheimer's disease (AD) is the leading cause of dementia in the elderly, but therapeutic options are lacking. Despite long being able to effectively treat the ill-effects of pathology present in various rodent models of AD, translation of these strategies to the clinic has so far been disappointing. One potential contributor to this situation is the fact that the vast majority of AD patients have other dementia-contributing comorbid pathologies, the most common of which are vascular in nature. This situation is modeled relatively infrequently in basic AD research, and almost never in preclinical studies. As part of our efforts to develop …

Potential And Limitations Of Using Stem Cells To Cure Alzheimer’S Disease: A Literature Review Of Its Potential And Ethical Limitations In Translation To Human Trials, Eleni Zivla

OUR Journal: ODU Undergraduate Research Journal

Alzheimer's disease has become one of the most significant, life-limiting illnesses of our time as a result of the rapid increase in the average life expectancy. To successfully develop a cure for this yet incurable disease, one must understand the pathology of Alzheimer’s disease. As found in recent research studies, a brain that is diagnosed with Alzheimer's is characterized by the presence of extracellular amyloid plaques composed of the amyloid-beta (Aβ) peptide and intracellular neurofibrillary tangles composed of the microtubule-associated protein: tau. In this literature review, several stem cell therapies are being reviewed as a potential cure for Alzheimer’s disease …

Ultrasonographic/Regional Muscle Measurements For Diagnosing Sarcopenia In Older Adults With And Without Dementia, Zekeri̇ya Ülger, Gözde Şengül Ayçi̇çek, Özgür Kara, Murat Kara

Turkish Journal of Medical Sciences

Background/aim: Sarcopenia and dementia are growing concerns among older adults that muscle and brain atrophy may cooccur. We aimed to compare the age-related loss of muscle mass by using ultrasound (US), and skeletal muscle mass index (SMI) by bioelectrical impedance analysis in older adults with and without dementia. Materials and methods: A total of 221 older adults aged ≥65 years were included in the study. The diagnosis of sarcopenia was established if low muscle mass according to either SMI or sonographic gastrocnemius (GC) muscle thickness was combined with low grip strength. The diagnosis of dementia was based on the National …

Editorial: Infection, Inflammation, And Neurodegeneration: A Critical Path To Alzheimer's Disease, Volume Ii., Roberta Mancuso, Simone Agostini, Denah Appelt, Brian J. Balin

PCOM Scholarly Papers

No abstract available

An Il1rl1 Genetic Variant Lowers Soluble St2 Levels And The Risk Effects Of Apoe-Ε4 In Female Patients With Alzheimer’S Disease, Yuanbing Jiang, Xiaopu Zhou, Hiu Yi Wong, Li Ouyang, Fanny C. F. Ip, Vicky M. N. Chau, Shun-Fat Lau, Wei Wu, Daniel Y. K. Wong, Heukjin Seo, Wing-Yu Fu, Nicole C. H. Lai, Yuewen Chen, Yu Chen, Estella P.S. Tong, Alzheimer’S Disease Neuroimaging Initiative, Vincent C. T. Mok, Timothy C. Y. Kwok, Kin Y. Mok, Maryam Shoai, Benoit Lehallier, Patricia Morán Losada, Eleanor O'Brien, Tenielle Porter, Simon Laws, John Hardy, Tony Wyss-Coray, Colin L. Masters, Amy K.Y. Fu, Nancy Y. Ip

Research outputs 2022 to 2026

Changes in the levels of circulating proteins are associated with Alzheimer’s disease (AD), whereas their pathogenic roles in AD are unclear. Here, we identified soluble ST2 (sST2), a decoy receptor of interleukin-33–ST2 signaling, as a new disease-causing factor in AD. Increased circulating sST2 level is associated with more severe pathological changes in female individuals with AD. Genome-wide association analysis and CRISPR–Cas9 genome editing identified rs1921622, a genetic variant in an enhancer element of IL1RL1, which downregulates gene and protein levels of sST2. Mendelian randomization analysis using genetic variants, including rs1921622, demonstrated that decreased sST2 levels lower AD …

Plasma P-Tau181/Aβ1-42 Ratio Predicts Aβ-Pet Status And Correlates With Csf-P-Tau181/Aβ1-42 And Future Cognitive Decline, Christopher J. Fowler, Erik Stoops, Stephanie R. Rainey-Smith, Eugeen Vanmechelen, Jeroen Vanbrabant, Nele Dewit, Kimberley Mauroo, Paul Maruff, Christopher C. Rowe, Jurgen Fripp, Qiao-Xin Li, Pierrick Bourgeat, Steven J. Collins, Ralph N. Martins, Colin L. Masters, James D. Doecke

Research outputs 2022 to 2026

Background: In Alzheimer's disease (AD), plasma amyloid beta (Aβ)1-42 and phosphorylated tau (p-tau) predict high amyloid status from Aβ positron emission tomography (PET); however, the extent to which combination of these plasma assays can predict remains unknown. Methods: Prototype Simoa assays were used to measure plasma samples from participants who were either cognitively normal (CN) or had mild cognitive impairment (MCI)/AD in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Results: The p-tau181/Aβ1-42 ratio showed the best prediction of Aβ-PET across all participants (area under the curve [AUC] = 0.905, 95% confidence interval [CI]: 0.86–0.95) and in CN (AUC = …

A Large-Scale Genome-Wide Cross-Trait Analysis Reveals Shared Genetic Architecture Between Alzheimer’S Disease And Gastrointestinal Tract Disorders, Emmanuel O. Adewuyi, Eleanor K. O'Brien, Dale R. Nyholt, Tenielle Porter, Simon Laws

Research outputs 2022 to 2026

Consistent with the concept of the gut-brain phenomenon, observational studies suggest a relationship between Alzheimer’s disease (AD) and gastrointestinal tract (GIT) disorders; however, their underlying mechanisms remain unclear. Here, we analyse several genome-wide association studies (GWAS) summary statistics (N = 34,652–456,327), to assess the relationship of AD with GIT disorders. Findings reveal a positive significant genetic overlap and correlation between AD and gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), gastritis-duodenitis, irritable bowel syndrome and diverticulosis, but not inflammatory bowel disease. Cross-trait meta-analysis identifies several loci (P_{meta-analysis} < 5 × 10⁻⁸) shared by AD and GIT disorders (GERD and PUD) including …

Plasma Aβ42/40 Ratio, P-Tau181, Gfap, And Nfl Across The Alzheimer's Disease Continuum: A Cross-Sectional And Longitudinal Study In The Aibl Cohort, Pratishtha Chatterjee, Steve Pedrini, James D. Doecke, Rohith Thota, Victor L. Villemagne, Vincent Doré, Abhay K. Singh, Penghao Wang, Stephanie Rainey-Smith, Christopher Fowler, Kevin Taddei, Hamid R. Sohrabi, Mark P. Molloy, David Ames, Paul Maruff, Christopher C. Rowe, Colin L. Masters, Ralph N. Martins, Aibl Research Group

Research outputs 2022 to 2026

Introduction:

Plasma amyloid beta (Aβ)1-42/Aβ1-40 ratio, phosphorylated-tau181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) are putative blood biomarkers for Alzheimer's disease (AD). However, head-to-head cross-sectional and longitudinal comparisons of the aforementioned biomarkers across the AD continuum are lacking.

Methods:

Plasma Aβ1-42, Aβ1-40, p-tau181, GFAP, and NfL were measured utilizing the Single Molecule Array (Simoa) platform and compared cross-sectionally across the AD continuum, wherein Aβ-PET (positron emission tomography)–negative cognitively unimpaired (CU Aβ−, n = 81) and mild cognitive impairment (MCI Aβ−, n = 26) participants were compared with Aβ-PET–positive participants across the AD continuum (CU Aβ+, n = …

Cerebrospinal Fluid Levels Of Fatty Acid–Binding Protein 3 Are Associated With Likelihood Of Amyloidopathy In Cognitively Healthy Individuals, Kunal Dhiman, Victor L. Villemagne, Christopher Fowler, Pierrick Bourgeat, Qiao-Xin Li, Steven Collins, Christopher C. Rowe, Colin L. Masters, David Ames, Kaj Blennow, Henrik Zetterberg, Ralph N. Martins, Veer Gupta

Research outputs 2022 to 2026

Introduction: Fatty acid–binding protein 3 (FABP3) is a biomarker of neuronal membrane disruption, associated with lipid dyshomeostasis—a notable Alzheimer's disease (AD) pathophysiological change. We assessed the association of cerebrospinal fluid (CSF) FABP3 levels with brain amyloidosis and the likelihood/risk of developing amyloidopathy in cognitively healthy individuals. Methods: FABP3 levels were measured in CSF samples of cognitively healthy participants, > 60 years of age (n = 142), from the Australian Imaging, Biomarkers & Lifestyle Flagship Study of Ageing (AIBL). Results: FABP3 levels were positively associated with baseline brain amyloid beta (Aβ) load as measured by standardized uptake value ratio (SUVR, standardized β …

Exploring Discordant Low Amyloid Beta And High Neocortical Tau Positron Emission Tomography Cases, Natasha Krishnadas, Vincent Doré, Simon M. Laws, Tenielle Porter, Fiona Lamb, Svetlana Bozinovski, Victor L. Villemagne, Christopher C. Rowe

Research outputs 2022 to 2026

Introduction: Neocortical 3R4R (3-repeat/4-repeat) tau aggregates are rarely observed in the absence of amyloid beta (Aβ). 18F-MK6240 binds specifically to the 3R4R form of tau that is characteristic of Alzheimer's disease (AD). We report four cases with negative Aβ, but positive tau positron emission tomography (PET) findings. Methods: All Australian Imaging, Biomarkers and Lifestyle study of aging (AIBL) study participants with Aβ (18F-NAV4694) and tau (18F-MK6240) PET scans were included. Centiloid < 25 defined negative Aβ PET (Aβ–). The presence of neocortical tau was defined quantitatively and visually. Results: Aβ– PET was observed in 276 participants. Four of these participants (one cognitively unimpaired [CU], two mild cognitive impairment [MCI], one AD) had tau tracer retention in a pattern consistent with Braak tau stages V to VI. Fluid biomarkers supported a diagnosis of AD. In silico analysis of APP, PSEN1, PSEN2, and MAPT genes did not identify relevant functional mutations. Discussion: Discordant cases were infrequent (1.4% of all Aβ– participants). In these cases, the Aβ PET ligand may not be detecting the Aβ that is present.