Medicine and Health Sciences Commons^™

Patterns And Implications Of Neurological Examination Findings In Autosomal Dominant Alzheimer Disease, Jonathan Vöglein, Nicolai Franzmeier, John C. Morris, Marianne Dieterich, Eric Mcdade, Mikael Simons, Oliver Preische, Anna Hofmann, Jason Hassenstab, Tammie L. Benzinger, Anne Fagan, James M. Noble, Sarah B. Berman, Neill R. Graff-Radford, Bernardino Ghetti, Martin R. Farlow, Jasmeer P. Chhatwal, Stephen Salloway, Chengjie Xiong, Celeste M. Karch, Nigel Cairns, Richard J. Perrin, Gregory Day, Ralph Martins, Raquel Sanchez-Valle, Hiroshi Mori, Hiroyuki Shimada, Takeshi Ikeuchi, Kazushi Suzuki, Peter R. Schofield, Colin L. Masters, Alison Goate, Virginia Buckles, Nick C. Fox, Patricio Chrem, Ricardo Allegri, John M. Ringman, Igor Yakushev, Christoph Laske, Mathias Jucker, Günter Höglinger, Randall L. Bateman, Adrian Danek, Johannes Levin, Dominantly Inherited Alzheimer Network

Research outputs 2022 to 2026

Introduction:

As knowledge about neurological examination findings in autosomal dominant Alzheimer disease (ADAD) is incomplete, we aimed to determine the frequency and significance of neurological examination findings in ADAD.

Methods:

Frequencies of neurological examination findings were compared between symptomatic mutation carriers and non mutation carriers from the Dominantly Inherited Alzheimer Network (DIAN) to define AD neurological examination findings. AD neurological examination findings were analyzed regarding frequency, association with and predictive value regarding cognitive decline, and association with brain atrophy in symptomatic mutation carriers.

Results:

AD neurological examination findings included abnormal deep tendon reflexes, gait disturbance, pathological cranial nerve examination findings, …

A Rapid Absorbance-Based Growth Assay To Screen The Toxicity Of Oligomer Aβ42 And Protect Against Cell Death In Yeast, Prashant Bharadwaj, Ralph Martins

Research outputs 2014 to 2021

Multiple lines of evidence show that soluble oligomer forms of amyloid β protein (Aβ42) are the most neurotoxic species in the brain and correlates with the degree of neuronal loss and cognitive deficit in Alzheimer's disease. Although many studies have used mammalian cells to investigate oligomer Aβ42 toxicity, the use of more simple eukaryotic cellular systems offers advantages for large-scale screening studies. We have previously established and validated budding yeast, Saccharomyces cerevisiae to be a simple and a robust model to study the toxicity of Aβ. Using colony counting based methods, oligomeric Aβ42 was shown to induce dose-dependent cell death …

Elecsys Csf Biomarker Immunoassays Demonstrate Concordance With Amyloid-Pet Imaging, James A. Doecke, Larry Ward, Samantha C. Burnham, Victor L. Villemagne, Qiao-Xin Li, Steven Collins, Christopher J. Fowler, Ekaterina Manuilova, Monika Widmann, Stephanie R. Rainey-Smith, Ralph N. Martins, Colin L. Masters, Aibl Research Group

Research outputs 2014 to 2021

Background: β-amyloid (Aβ) positron emission tomography (PET) imaging is currently the only Food and Drug Administration-approved method to support clinical diagnosis of Alzheimer's disease (AD). However, numerous research studies support the use of cerebrospinal fluid (CSF) biomarkers, as a cost-efficient, quick and equally valid method to define AD pathology. Methods: Using automated Elecsys® assays (Roche Diagnostics) for Aβ (1-42) (Aβ42), Aβ (1-40) (Aβ40), total tau (tTau) and phosphorylated tau (181P) (pTau), we examined CSF samples from 202 participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing cohort, to demonstrate the concordance with pathological AD via PET imaging. …

Blood-Based Molecular Biomarkers For Alzheimer's Disease, Henrik Zetterberg, Samantha C. Burnham

Research outputs 2014 to 2021

A major barrier to the effective conduct of clinical trials of new drug candidates against Alzheimer's disease (AD) and to identifying patients for receiving future disease-modifying treatments is the limited capacity of the current health system to find and diagnose patients with early AD pathology. This may be related in part to the limited capacity of the current health systems to select those people likely to have AD pathology in order to confirm the diagnosis with available cerebrospinal fluid and imaging biomarkers at memory clinics. In the current narrative review, we summarize the literature on candidate blood tests for AD …

Amyloid Β–Associated Cognitive Decline In The Absence Of Clinical Disease Progression And Systemic Illness, Karra Harrington, Yen Lim, David Ames, Jason Hassenstab, Simon Laws, Ralph Martins, Stephanie Rainey-Smith, Joanne Robertson, Christopher Rowe, Olivier Salvado, Vincent Dore, Victor Villemagne, Peter Snyder, Colin Masters, Paul Maruff, Aibl Research Group

Research outputs 2014 to 2021

Introduction

High levels of amyloid β (Aβ) are associated with cognitive decline in cognitively normal (CN) older adults. This study investigated the nature of cognitive decline in healthy individuals who did not progress to mild cognitive impairment or dementia.

Method

Cognition was measured over 72 months and compared between low (Aβ−) and high (Aβ+) CN older adults (n = 335) who did not progress to mild cognitive impairment or dementia and who remained free of severe or uncontrolled systemic illness.

Results

Compared to the Aβ− group, the Aβ+ group showed no cognitive impairment at baseline but showed substantial decline …

Guidelines For The Standardization Of Preanalytic Variables For Blood-Based Biomarker Studies In Alzheimer's Disease Research, Sid O'Bryant, Veer Gupta, Kim Henriksen, Melissa Edwards, Andreas Jeromin, Simone Lista, Chantal Bazenet, Holly Soares, Simon Lovestone, Harald Hampel, Thomas Montine, Kaj Blennow, Tatiana Foroud, Maria Carrillo, Neill Graff-Radford, Christoph Laske, Monique Breteler, Leslie Shaw, John Q. Trojanowski, Nicole Schupf, Robert A. Rissman, Anne M. Fagan, Pankaj Oberoi, Robert Umek, Michael W. Weiner, Paula Grammas, Holly Posner, Ralph Martins

Research outputs 2014 to 2021

The lack of readily available biomarkers is a significant hindrance toward progressing to effective therapeutic and preventative strategies for Alzheimer's disease (AD). Blood-based biomarkers have potential to overcome access and cost barriers and greatly facilitate advanced neuroimaging and cerebrospinal fluid biomarker approaches. Despite the fact that preanalytical processing is the largest source of variability in laboratory testing, there are no currently available standardized preanalytical guidelines. The current international working group provides the initial starting point for such guidelines for standardized operating procedures (SOPs). It is anticipated that these guidelines will be updated as additional research findings become available. The statement …

Amyloid-Related Memory Decline In Preclinical Alzheimer's Disease In Dependent On Apoe Ε4 And Is Detectable Over 18-Months, Christine Thai, Yen Ying Lim, Victor L. Villemagne, Simon Laws, David Ames, Kathryn A. Ellis, Stephanie Rainey-Smith, Ralph Martins, Colin L. Masters, Christopher C. Rowe, Paul Maruff, Australian Imaging, Biomarkers And Lifestyle (Aibl) Research Group

Research outputs 2014 to 2021

High levels of β-amyloid (Aβ) in the brain and carriage of the APOE ε4 allele have each been linked to cognitive impairment in cognitively normal (CN) older adults. The aim of this study was to investigate the relationship between cerebral Aβ level, APOE ε4 carrier status, and cognitive decline over 18 monthes, in 317 cognitively healthy (CN) older adults (47% males, 52.4% females) aged between 60 and 89 years (Mean = 69.9, SC = 6.8). Cognition was assessed using the Cogstate Brief Battery (CBB) and the California Verbal Learning Test, Second Edition (CVLT-II). Planned comparisons indicated that CN older adults …

Follow-Up Plasma Apolipoprotein E Levels In The Australian Imaging, Biomarkers And Lifestyle Flagship Study Of Ageing (Aibl) Cohort, Veer B. Gupta, V.B, Andrea C. Wilson, Samantha Burnham, Eugene Hone, Steve Pedrini, Simon M. Laws, Wei L.F. Lim, Alan Rembach, Stephanie Rainey-Smith, David Ames, Lynne Cobiac, S L. Macaulay, Colin L. Masters, Christopher C. Rowe, Ashley I. Bush, Ralph Martins, Aibl Research Group

Research outputs 2014 to 2021

Introduction: Alzheimer's disease (AD) is a growing socioeconomic problem worldwide. Early diagnosis and prevention of this devastating disease have become a research priority. Consequently, the identification of clinically significant and sensitive blood biomarkers for its early detection is very important. Apolipoprotein E (APOE) is a well-known and established genetic risk factor for late-onset AD; however, the impact of the protein level on AD risk is unclear. We assessed the utility of plasma ApoE protein as a potential biomarker of AD in the large, well-characterised Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) cohort. Methods: Total plasma ApoE levels were …

Biomarkers Of Alzheimer's Disease Risk In Peripheral Tissues; Focus On Buccal Cells, Maxime François, Wayne Leifert, Ralph Martins, Philip Thomas, Michael Fenech

Research outputs 2014 to 2021

Alzheimer's disease (AD) is a progressive degenerative disorder of the brain and is the most common form of dementia. To-date no simple, inexpensive and minimally invasive procedure is available to confirm with certainty the early diagnosis of AD prior to the manifestations of symptoms characteristic of the disease. Therefore, if population screening of individuals is to be performed, more suitable, easily accessible tissues would need to be used for a diagnostic test that would identify those who exhibit cellular pathology indicative of mild cognitive impairment (MCI) and AD risk so that they can be prioritized for primary prevention. This need …

Effect Of Bdnf Val66met On Memory Decline And Hippocampal Atrophy In Prodromal Alzheimer's Disease: A Preliminary Study, Yen Y. Lim, Victor L. Villemagne, Simon M. Laws, David Ames, Robert H. Pietrzak, Kathryn A. Ellis, Karra Harrington, Pierrick Bourgeat, Ashley I. Bush, Ralph N. Martins, Colin L. Masters, Christopher C. Rowe, Paul Maruff

Research outputs 2014 to 2021

Objective: Cross-sectional genetic association studies have reported equivocal results on the relationship between the brain-derived neurotrophic factor (BDNF) Val66Met and risk of Alzheimer's disease (AD). As AD is a neurodegenerative disease, genetic influences may become clearer from prospective study. We aimed to determine whether BDNF Val66Met polymorphism influences changes in memory performance, hippocampal volume, and Aβ accumulation in adults with amnestic mild cognitive impairment (aMCI) and high Aβ. Methods: Thirty-four adults with aMCI were recruited from the Australian, Imaging, Biomarkers and Lifestyle (AIBL) Study. Participants underwent PiB-PET and structural MRI neuroimaging, neuropsychological assessments and BDNF genotyping at baseline, 18 month, …

An Anemia Of Alzheimer's Disease, N G. Faux, A Rembach, J Wiley, K A. Ellis, D Ames, C J. Fowler, Ralph N. Martins, K K. Pertile, R L. Rumble, B Trounson, C L. Masters, A I. Bush

Research outputs 2014 to 2021

Lower hemoglobin is associated with cognitive impairment and Alzheimer's disease (AD). Since brain iron homeostasis is perturbed in AD, we investigated whether this is peripherally reflected in the hematological and related blood chemistry values from the Australian Imaging Biomarker and Lifestyle (AIBL) study (a community-based, cross-sectional cohort comprising 768 healthy controls (HC), 133 participants with mild cognitive impairment (MCI) and 211 participants with AD). We found that individuals with AD had significantly lower hemoglobin, mean cell hemoglobin concentrations, packed cell volume and higher erythrocyte sedimentation rates (adjusted for age, gender, APOE-ε4 and site). In AD, plasma iron, transferrin, transferrin saturation …

Retinal Vascular Biomarkers For Early Detection And Monitoring Of Alzheimer's Disease, Shawn Frost, Yogi Kanagasingam, Hamid Sohrabi, J Vignarajan, P Bourgeat, Olivier Salvado, Victor Villemagne, Christopher Rowe, S Lance Macaulay, Cassandra Szoeke, Kathryn A. Ellis, David Ames, Colin L. Masters, Stephanie Rainey-Smith, Ralph N. Martins

Research outputs 2013

The earliest detectable change in Alzheimer's disease (AD) is the buildup of amyloid plaque in the brain. Early detection of AD, prior to irreversible neurological damage, is important for the efficacy of current interventions as well as for the development of new treatments. Although PiB-PET imaging and CSF amyloid are the gold standards for early AD diagnosis, there are practical limitations for population screening. AD-related pathology occurs primarily in the brain, but some of the hallmarks of the disease have also been shown to occur in other tissues, including the retina, which is more accessible for imaging. Retinal vascular changes …

Multiplex Biomarkers In Blood, Veer Bala Bala Gupta, Ramani Sundaram, Ralph N. Martins

Research outputs 2013

Advances in the field of blood biomarker discovery will help in identifying Alzheimer's disease in its preclinical stage, allowing treatment to be initiated before irreversible damage occurs. This review discusses some recent past and current approaches being taken by researchers in the field. Individual blood biomarkers have been unsuccessful in defining the disease pathology, progression and thus diagnosis. This directs to the need for discovering a multiplex panel of blood biomarkers as a promising approach with high sensitivity and specificity for early diagnosis. However, it is a great challenge to standardize a worldwide blood biomarker panel due to the innate …

Predictors Of Rapid Cognitive Decline In Alzheimer's Disease: Results From The Australian Imaging, Biomarkers And Lifestyle (Aibl) Study Of Ageing, A Sona, P Zhang, D Ames, A I Bush, N T Lautenschlager, Ralph Martins, C L Masters, C C Rowe, C Szoeke, Kevin Taddei, Kathryn A Ellis

Research outputs 2012

Background: The AIBL study, which commenced in November 2006, is a two-center prospective study of a cohort of 1112 volunteers aged 60+. The cohort includes 211 patients meeting NINCDS-ADRDA criteria for Alzheimer's disease (AD) (180 probable and 31 possible). We aimed to identify factors associated with rapid cognitive decline over 18 months in this cohort of AD patients. Methods: We defined rapid cognitive decline as a drop of 6 points or more on the Mini-Mental State Examination (MMSE) between baseline and 18-month follow-up. Analyses were also conducted with a threshold of 4, 5, 7 and 8 points, as well as …

Altered Expression Of Alzheimer's Disease-Related Proteins In Male Hypogonadal Mice, Eleanor S. Drummond, Ralph Martins, D J Handelsman, A R Harvey

Research outputs 2012

Age-related depletion of estrogens and androgens is associated with an increase in Alzheimer's disease (AD) brain pathology and diminished cognitive function. Here we investigated AD-associated molecular and cellular changes in brains of aged hypogonadal (hpg) male and female mice. hpg Mice have a spontaneous, inactivating genetic mutation in the GnRH gene resulting in lifelong deficiency of gonadotropins and gonadal sex hormones. Western blot analysis revealed low levels of amyloid precursor protein and high levels of presenilin 1, amyloid precursor protein C-terminal fragment, and β-amyloid 42 in brains of aged male, but not female, hpg mice. Changes were confined to the …

Lifestyle And Late Life Cognitive Health: Sufficient Evidence To Act Now?, Bruce Barber, D Ames, Kathryn Ellis, Ralph Martins, C Masters, C Szoeke

Research outputs 2012

Not available

Clinical And Biomarker Changes In Dominantly Inherited Alzheimer's Disease, R J Bateman, C Xiong, T L Benzinger, A M Fagan, A Goate, N C Fox, D S Marcus, N J Cairns, X Xie, T M Blazey, D M Holtzman, A Santacruz, V Buckles, A Oliver, K Moulder, P M Aisen, B Ghetti, W M Klunk, E Mcdade, Ralph Martins, C M Masters, R Mayeux, J M Ringman, M M Rossor, P M Schofield, R M Sperling, S Salloway, J M Morris

Research outputs 2012

BACKGROUND: The order and magnitude of pathologic processes in Alzheimer's disease are not well understood, partly because the disease develops over many years. Autosomal dominant Alzheimer's disease has a predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease. METHODS: In this prospective, longitudinal study, we analyzed data from 128 participants who underwent baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. We used the participant's age at baseline assessment and the parent's age at the onset of symptoms of Alzheimer's disease to …

Olfactory Discrimination Predicts Cognitive Decline Among Community-Dwelling Older Adults, Hamid Sohrabi, Kristyn Bates, Mg Weinborn, A N Johnston, A Bahramian, Kevin Taddei, Simon Laws, Mark Rodrigues, Michael Morici, Matthew Howard, Georgia Martins, A Mackay-Sim, Se Gandy, Ralph Martins

Research outputs 2012

The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46-86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions …