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Higher Coffee Consumption Is Associated With Slower Cognitive Decline And Less Cerebral Aβ-Amyloid Accumulation Over 126 Months: Data From The Australian Imaging, Biomarkers, And Lifestyle Study, Samantha L. Gardener, Stephanie R. Rainey-Smith, Victor L. Villemagne, Jurgen Fripp, Vincent Doré, Pierrick Bourgeat, Kevin Taddei, Christopher Fowler, Colin L. Masters, Paul Maruff, Christopher C. Rowe, David Ames, Ralph N. Martins, Aibl Investigators

Research outputs 2014 to 2021

Background:

Worldwide, coffee is one of the most popular beverages consumed. Several studies have suggested a protective role of coffee, including reduced risk of Alzheimer’s disease (AD). However, there is limited longitudinal data from cohorts of older adults reporting associations of coffee intake with cognitive decline, in distinct domains, and investigating the neuropathological mechanisms underpinning any such associations.

Methods: The aim of the current study was to investigate the relationship between self-reported habitual coffee intake, and cognitive decline assessed using a comprehensive neuropsychological battery in 227 cognitively normal older adults from the Australian Imaging, Biomarkers, and Lifestyle (AIBL) study, over …

Therapeutic Potential Of Mitophagy-Inducing Microflora Metabolite, Urolithin A For Alzheimer’S Disease, Dona Pamoda W. Jayatunga, Eugene Hone, Harjot Khaira, Taciana Lunelli, Harjinder Singh, Gilles J. Guillemin, Binosha Fernando, Manohar L. Garg, Giuseppe Verdile, Ralph N. Martins

Research outputs 2014 to 2021

Mitochondrial dysfunction including deficits of mitophagy is seen in aging and neuro-degenerative disorders including Alzheimer’s disease (AD). Apart from traditionally targeting amyloid beta (Aβ), the main culprit in AD brains, other approaches include investigating impaired mitochondrial pathways for potential therapeutic benefits against AD. Thus, a future therapy for AD may focus on novel candidates that enhance optimal mitochondrial integrity and turnover. Bi-oactive food components, known as nutraceuticals, may serve as such agents to combat AD. Uro-lithin A is an intestinal microbe-derived metabolite of a class of polyphenols, ellagitannins (ETs). Urolithin A is known to exert many health benefits. Its antioxidant, …

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 …

Evaluation Of Gammah2ax In Buccal Cells As A Molecular Biomarker Of Dna Damage In Alzheimer’S Disease In The Aibl Study Of Ageing, Mohammad Sabbir Siddiqui, Maxime Francois, Stephanie Rainey-Smith, Ralph Martins, Colin L. Masters, David Ames, Christopher C. Rowe, Lance S. Macaulay, Michael F. Fenech, Wayne R. Leifert

Research outputs 2014 to 2021

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. In response to double-stranded breaks (DSBs) in chromosomal DNA, H2AX (a member of histone H2A family) becomes phosphorylated to form γH2AX. Although increased levels of γH2AX have been reported in the neuronal nuclei of Alzheimer’s disease (AD) patients, the understanding of γH2AX responses in buccal nuclei of individuals with mild cognitive impairment (MCI) and AD remain unexplored. In the current study, endogenous γH2AX was measured in buccal cell nuclei from MCI (n = 18) or AD (n = 16) patients and in healthy controls (n = 17) using laser scanning cytometry …

Serum Hepcidin Levels In Cognitively Normal Older Adults With High Neocortical Amyloid-Beta Load, Pratishtha Chatterjee, Maryam Mohammadi, Kathryn Goozee, Tejal Shah, Hamid R. Sohrabi, Cintia B. Dias, Kaikai Shen, Prita R. Asih, Preeti Dave, Steve Pedrini, Nicholas J. Ashton, Abdul Hye, Kevin Taddei, David B. Lovejoy, Henrik Zetterberg, Kaj Blennow, Ralph Martins

Research outputs 2014 to 2021

Background/Objective:

Hepcidin, an iron-regulating hormone, suppresses the release of iron by binding to the iron exporter protein, ferroportin, resulting in intracellular iron accumulation. Given that iron dyshomeostasis has been observed in Alzheimer’s disease (AD) together with elevated serum hepcidin levels, the current study examined whether elevated serum hepcidin levels are an early event in AD pathogenesis by measuring the hormone in cognitively normal older adults at risk of AD, based on high neocortical amyloid-β load (NAL).

Methods:

Serum hepcidin levels in cognitively normal participants (n = 100) aged between 65–90 years were measured using ELISA. To evaluate NAL, all …

Relationships Between Plasma Lipids Species, Gender, Risk Factors And Alzheimer’S Disease, Wei Ling Florence Lim, Kevin Huynh, Pratishtha Chatterjee, Ian Martins, Kaushala S. Jayawardana, Corey Giles, Natalie A. Mellett, Simon M. Laws, Ashley I. Bush, Christopher C. Rowe, Victor L. Villemagne, David Ames, Brian G. Drew, Colin L. Masters, Peter J. Meikle, Ralph Martins, Australian Imaging, Biomarker & Lifestyle Research Group

Research outputs 2014 to 2021

Background:

Lipid metabolism is altered in Alzheimer’s disease (AD); however, the relationship between AD risk factors (age, APOE ɛ4, and gender) and lipid metabolism is not well defined.

Objective:

We investigated whether altered lipid metabolism associated with increased age, gender, and APOE status may contribute to the development of AD by examining these risk factors in healthy controls and also clinically diagnosed AD individuals.

Methods:

We performed plasma lipidomic profiling (582 lipid species) of the Australian Imaging, Biomarkers and Lifestyle flagship study of aging cohort (AIBL) using liquid chromatography-mass spectrometry. Linear regression and interaction analysis were used to explore …

Docosahexaenoic Acid-Rich Fish Oil Supplementation Reduces Kinase Associated With Insulin Resistance In Overweight And Obese Midlife Adults, Rohith N. Thota, Jessica I. Rosato, Tracy L. Burrows, Cintia B. Dias, Kylie A. Abbott, Ralph N. Martins, Manohar L. Garg

Research outputs 2014 to 2021

Targeting kinases linked to insulin resistance (IR) and inflammation may help in reducing the risk of type 2 diabetes (T2D) and Alzheimer’s disease (AD) in its early stages. This study aimed to determine whether DHA-rich fish oil supplementation reduces glycogen synthase kinase (GSK-3), which is linked to both IR and AD. Baseline and post-intervention plasma samples from 58 adults with abdominal obesity (Age: 51.7 ± 1.7 years, BMI: 31.9 ± 0.8 kg/m2) were analysed for outcome measures. Participants were allocated to 2 g DHA-rich fish oil capsules (860 mg DHA + 120 mg EPA) (n = 31) or placebo capsules …

Bilingualism Is Associated With A Delayed Onset Of Dementia But Not With A Lower Risk Of Developing It: A Systematic Review With Meta-Analyses, Stefano Brini, Hamid R. Sohrabi, Jeffrey J. Hebert, Mitchell R.L. Forrest, Matti Laine, Heikki Hämäläinen, Mira Karrasch, Jeremiah Peiffer, Ralph Martins, Timothy J. Fairchild

Research outputs 2014 to 2021

Some studies have linked bilingualism with a later onset of dementia, Alzheimer’s disease (AD), and mild cognitive impairment (MCI). Not all studies have observed such relationships, however. Differences in study outcomes may be due to methodological limitations and the presence of confounding factors within studies such as immigration status and level of education. We conducted the first systematic review with meta-analysis combining cross-sectional studies to explore if bilingualism might delay symptom onset and diagnosis of dementia, AD, and MCI. Primary outcomes included the age of symptom onset, the age at diagnosis of MCI or dementia, and the risk of developing …

A Polygenic Risk Score Derived From Episodic Memory Weighted Genetic Variants Is Associated With Cognitive Decline In Preclinical Alzheimer’S Disease, Tenielle Porter, Samantha C. Burnham, Greg Savage, Yen Ying Lim, Paul Maruff, Lidija Milicic, Madeline Peretti, David Ames, Colin L. Masters, Ralph N. Martins, Stephanie Rainey-Smith, Christopher C. Rowe, Olivier Salvado, Kevin Taddei, David Groth, Guiseppe Verdile, Victor L. Villemagne, Simon M. Laws

Research outputs 2014 to 2021

Studies of Alzheimer’s disease risk-weighted polygenic risk scores (PRSs) for cognitive performance have reported inconsistent associations. This inconsistency is particularly evident when PRSs are assessed independent of APOE genotype. As such, the development and assessment of phenotype-specific weightings to derive PRSs for cognitive decline in preclinical AD is warranted. To this end a episodic memory-weighted PRS (emPRS) was derived and assessed against decline in cognitive performance in 226 healthy cognitively normal older adults with high brain Aβ-amyloid burden participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. The effect size for decline in a verbal episodic memory …

Changes In The Plasma Proteome At Asymptomatic And Symptomatic Stages Of Autosomal Dominant Alzheimer's Disease, Julia Muenchhoff, Anne Poljak, Anbupalam Thalamuthu, Veer Gupta, Pratishtha Chatterjee, Mark Raftery, Colin Masters, John Morris, Randall Bateman, Anne Fagan, Ralph Martins, Perminder Sachdev

Research outputs 2014 to 2021

The autosomal dominant form of Alzheimer's disease (ADAD) is far less prevalent than late onset Alzheimer's disease (LOAD), but enables well-informed prospective studies, since symptom onset is near certain and age of onset is predictable. Our aim was to discover plasma proteins associated with early AD pathology by investigating plasma protein changes at the asymptomatic and symptomatic stages of ADAD. Eighty-one proteins were compared across asymptomatic mutation carriers (aMC, n = 15), symptomatic mutation carriers (sMC, n = 8) and related noncarriers (NC, n = 12). Proteins were also tested for associations with cognitive measures, brain amyloid deposition and glucose …