Medicine and Health Sciences Commons^™

Altered Levels Of Blood Proteins In Alzheimer's Disease Longitudinal Study: Results From Australian Imaging Biomarkers Lifestyle Study Of Ageing Cohort, Veer B. Gupta, Eugene Hone, Steve Pedrini, James D. Doecke, Sid E. O'Bryant, Ian James, Ashley I. Bush, Christopher C. Rowe, Victor L. Villemagne, David Ames, Colin L. Masters, Ralph N. Martins

Research outputs 2014 to 2021

Introduction

A blood-based biomarker panel to identify individuals with preclinical Alzheimer's disease (AD) would be an inexpensive and accessible first step for routine testing.

Methods

We analyzed 14 biomarkers that have previously been linked to AD in the Australian Imaging Biomarkers lifestyle longitudinal study of aging cohort.

Results

Levels of apolipoprotein J (apoJ) were higher in AD individuals compared with healthy controls at baseline and 18 months (P =.0003) and chemokine-309 (I-309) were increased in AD patients compared to mild cognitive impaired individuals over 36 months (P =.0008).

Discussion

These data suggest that apoJ may have potential in the context …

Caffeine Consumption With Relevance To Type 3 Diabetes And Accelerated Brain Aging, I. J. Martins

Research outputs 2014 to 2021

Major interests in caffeine consumption has increased with the alarming increase in the global NAFLD epidemic relevant to increased transport of caffeine to the brain with the induction of Type 3 diabetes. Specific nutritional diets are essential to maintain hepatic caffeine metabolism to facilitate rapid Aβ clearance in the periphery and to maintain the effects of drugs such as statins to reduce toxic Aβ formation not only in Type 3 diabetes but to various neurological diseases. Anti-aging gene Sirt 1 is responsible for brain Aβ and caffeine metabolism and inactivation of Sirt 1 by unhealthy diets is now relevant to …

Insulin Resistance Is Associated With Reductions In Specific Cognitive Domains And Increases In Csf Tau In Cognitively Normal Adults, Simon M. Laws, Scott Gaskin, Amy Woodfield, Velandai K. Srikanth, David G. Bruce, Paul E. Fraser, Tenielle Porter, Philip N. Newsholme, Nadeeja Wijesekara, Samantha C. Burnham, Vincent Doré, Qiaoxin Li, Paul T. Maruff, Colin L. Masters, Stephanie R. Rainey-Smith, Christopher C. Rowe, Olivier Salvado, Victor L. Villemagne, Ralph N. Martins, Giuseppe Verdile

Research outputs 2014 to 2021

Growing evidence supports the hypothesis that type 2 diabetes (T2D) increases the risk of developing dementia. Experimental evidence from mouse models demonstrates that the induction of T2D/insulin resistance (IR) can promote the accumulation of Alzheimer's disease (AD) pathological features. However, the association of T2D with pathological and clinical phenotypes in humans is unclear. Here we investigate the relationship of indices of IR (HOMA-IR) and pancreatic β-cell function (HOMA-B) with cognitive performance across several domains (Verbal/Visual Episodic Memory, Executive Function, Language and a measure of Global cognition) and AD biomarkers (CSF Aβ42, T-tau/P-tau, hippocampal volume and neocortical Aβ-amyloid burden). We reveal …

Comparing Biological Markers Of Alzheimer's Disease Across Blood Fraction And Platforms: Comparing Apples To Oranges, Sid E. O'Bryant, Simone Lista, Robert A. Rissman, Melissa Edwards, Fan Zhang, James Hall, Herik Zetterberg, Simon Lovestone, Veer Bular Gupta, Neill Graff-Radford, Ralph N. Martins, Andreas Jeromin, Stephen Waring, Esther Oh, Mitchel Kling, Laura D. Baker, Harald Hampel

Research outputs 2014 to 2021

Introduction:

This study investigated the comparability of potential Alzheimer's disease (AD) biomarkers across blood fractions and assay platforms.

Methods:

Nonfasting serum and plasma samples from 300 participants (150 AD patients and 150 controls) were analyzed. Proteomic markers were obtained via electrochemiluminescence or Luminex technology. Comparisons were conducted via Pearson correlations. The relative importance of proteins within an AD diagnostic profile was examined using random forest importance plots.

Results:

On the Meso Scale Discovery multiplex platform, 10 of the 21 markers shared > 50% of the variance across blood fractions (serum amyloid A R2 = 0.99, interleukin (IL)10 R2 = 0.95, fatty …

Finding Chemopreventatives To Reduce Amyloid Beta In Yeast, Ian Macreadie, Costa Arvanitis, Prashant Bharadwaj

Research outputs 2014 to 2021

Alzheimer's disease (AD) is the most common form of age-related dementia with the latest report (WorldAlzheimerReport, 2015) showing 46.8 million people are currently affected by dementia. That number is expected to double every 20 years unless there is effective therapeutic intervention.

The Effects Of Latrepirdine On Amyloid-Β Aggregation And Toxicity, Tenielle Porter, Prashant Bharadwaj, David Groth, Adrian Paxman, Simon Laws, Ralph Martins, Guiseppe Verdile

Research outputs 2014 to 2021

Latrepirdine (DimebonTM) has been demonstrated to be a neuroprotective and cognition improving agent in neurodegenerative diseases that feature protein aggregation and deposition, such as Alzheimer's disease (AD). The accumulation of amyloid-β (Aβ) protein aggregates is a key event in the neurodegenerative process in AD. This study explores if latrepirdine modulation of protein aggregation contributes to its neuroprotective mechanism of action. Assessment of neuronal cell death showed that there was a significant reduction in lactate dehydrogenase release at an equimolar ratio of Aβ:latrepirdine and with lower concentrations of latrepirdine. The ability of latrepirdine to alter the formation of Aβ42 aggregates was …

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 …

Altered Cytological Parameters In Buccal Cells From Individuals With Mild Cognitive Impairment And Alzheimer's Disease, Maxime François, Wayne Leifert, Jane Hecker, Jeffrey Faunt, Ralph Martins, Philip Thomas, Michael Fenech

Research outputs 2014 to 2021

Previous studies have shown that mild cognitive impairment (MCI) may be reflective of the early stages of more pronounced neurodegenerative disorders such as Alzheimer's disease (AD). There is a need for a minimally invasive and inexpensive diagnostic to identify those who exhibit cellular pathology indicative of MCI and AD risk so that they can be prioritized for primary preventative measures. The hypothesis was that a minimally invasive approach using cytological markers in isolated buccal mucosa cells can be used to identify individuals of both MCI and AD. An automated buccal cell assay was developed using laser scanning cytometry (LSC) to …