%0 Journal Article %J J Alzheimers Dis %D 2018 %T Associations of Dietary Protein and Fiber Intake with Brain and Blood Amyloid-β. %A Fernando, W M A D Binosha %A Rainey-Smith, Stephanie R %A Gardener, Samantha L %A Villemagne, Victor L %A Burnham, Samantha C %A Macaulay, S Lance %A Brown, Belinda M %A Gupta, Veer Bala %A Sohrabi, Hamid R %A Weinborn, Michael %A Taddei, Kevin %A Laws, Simon M %A Goozee, Kathryn %A Ames, David %A Fowler, Christopher %A Maruff, Paul %A Masters, Colin L %A Salvado, Olivier %A Rowe, Christopher C %A Martins, Ralph N %K Aged %K Alzheimer Disease %K Amyloid beta-Peptides %K Australia %K Biomarkers %K Brain %K Cognition %K Cohort Studies %K Cross-Sectional Studies %K Dietary Fiber %K Dietary Proteins %K Female %K Humans %K Logistic Models %K Male %K Middle Aged %K Neuropsychological Tests %K Positron-Emission Tomography %X

Accumulating evidence suggests a diet high in protein and fiber may confer some protection against Alzheimer's disease (AD). However, no human studies to-date have assessed the relationship between protein and fiber intake, and plasma and brain amyloid-β (Aβ). Consequently, this cross-sectional study, investigated the association of self-reported dietary intakes of protein and fiber, with plasma and brain Aβ burden (n = 541, and n = 162 respectively), in a well-characterized cohort of cognitively normal older adults, drawn from the larger Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. We observed 12.59 and 8.43 higher odds of 'high' brain Aβ burden (PiB PET SUVR≥1.5) if protein intake fell in the lowest and middle tertile, respectively, compared to the highest tertile (p = 0.008; p = 0.013). Thus, in this cohort, the more protein consumed, the less likelihood of 'high' Aβ burden in the brain. No other significant associations were observed. The results of this study highlight the potentially protective impact of high dietary protein intake on brain Aβ burden in older adults, before objective memory decline is apparent. While longitudinal validation is required, these findings may assist in the development of dietary approaches aimed at preventing or delaying AD onset.

%B J Alzheimers Dis %V 61 %P 1589-1598 %8 2018 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/29376865?dopt=Abstract %R 10.3233/JAD-170742 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Concordance Between Cerebrospinal Fluid Biomarkers with Alzheimer's Disease Pathology Between Three Independent Assay Platforms. %A Doecke, James D %A Rembach, Alan %A Villemagne, Victor L %A Varghese, Shiji %A Rainey-Smith, Stephanie %A Sarros, Shannon %A Evered, Lisbeth A %A Fowler, Christopher J %A Pertile, Kelly K %A Rumble, Rebecca L %A Trounson, Brett %A Taddei, Kevin %A Laws, Simon M %A Macaulay, S Lance %A Bush, Ashley I %A Ellis, Kathryn A %A Martins, Ralph %A Ames, David %A Silbert, Brendan %A Vanderstichele, Hugo %A Masters, Colin L %A Darby, David G %A Li, Qiao-Xin %A Collins, Steven %K Aged %K Aged, 80 and over %K Alzheimer Disease %K Amyloid beta-Peptides %K Biomarkers %K Cognition Disorders %K Female %K Humans %K Male %K Mental Status Schedule %K Peptide Fragments %K Positron-Emission Tomography %K ROC Curve %K tau Proteins %X

BACKGROUND: To enhance the accuracy of clinical diagnosis for Alzheimer's disease (AD), pre-mortem biomarkers have become increasingly important for diagnosis and for participant recruitment in disease-specific treatment trials. Cerebrospinal fluid (CSF) biomarkers provide a low-cost alternative to positron emission tomography (PET) imaging for in vivo quantification of different AD pathological hallmarks in the brains of affected subjects; however, consensus around the best platform, most informative biomarker and correlations across different methodologies are controversial.

OBJECTIVE: Assessing levels of Aβ-amyloid and tau species determined using three different versions of immunoassays, the current study explored the ability of CSF biomarkers to predict PET Aβ-amyloid (32 Aβ-amyloid-and 45 Aβ-amyloid+), as well as concordance between CSF biomarker levels and PET Aβ-amyloid imaging.

METHODS: Prediction and concordance analyses were performed using a sub-cohort of 77 individuals (48 healthy controls, 15 with mild cognitive impairment, and 14 with AD) from the Australian Imaging Biomarker and Lifestyle study of aging.

RESULTS: Across all three platforms, the T-tau/Aβ42 ratio biomarker had modestly higher correlation with SUVR/BeCKeT (ρ= 0.69-0.8) as compared with Aβ42 alone (ρ= 0.66-0.75). Differences in CSF biomarker levels between the PET Aβ-amyloid-and Aβ-amyloid+ groups were strongest for the Aβ42/Aβ40 and T-tau/Aβ42 ratios (p < 0.0001); however, comparison of predictive models for PET Aβ-amyloid showed no difference between Aβ42 alone and the T-tau/Aβ42 ratio.

CONCLUSION: This study confirms strong concordance between CSF biomarkers and PET Aβ-amyloid status is independent of immunoassay platform, supporting their utility as biomarkers in clinical practice for the diagnosis of AD and for participant enrichment in clinical trials.

%B J Alzheimers Dis %V 61 %P 169-183 %8 2018 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/29171991?dopt=Abstract %R 10.3233/JAD-170128 %0 Journal Article %J J Alzheimers Dis %D 2016 %T The Effects of Latrepirdine on Amyloid-β Aggregation and Toxicity. %A Porter, Tenielle %A Bharadwaj, Prashant %A Groth, David %A Paxman, Adrian %A Laws, Simon M %A Martins, Ralph N %A Verdile, Giuseppe %K Amyloid beta-Peptides %K Analysis of Variance %K Antipsychotic Agents %K Cell Line, Tumor %K Dose-Response Relationship, Drug %K Drug Interactions %K Humans %K Indoles %K L-Lactate Dehydrogenase %K Microscopy, Atomic Force %K Neuroblastoma %K Peptide Fragments %K Protein Aggregates %X

Latrepirdine (Dimebon) 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 assessed by thioflavin-T fluorescence, western immunoblotting and atomic force microscopy (AFM). Despite showing a reduction in thioflavin-T fluorescence with latrepirdine treatment, indicating a decrease in aggregation, immunoblotting and AFM showed a modest increase in both the formation and size of Aβ aggregates. The discrepancies between thioflavin-T and the other assays are consistent with previous evidence that cyclic molecules can interfere with thioflavin-T binding of amyloid protein preparations. The ability of latrepirdine to modulate Aβ aggregation appears to be independent of its neuroprotective effects, and is unlikely to be a mechanism by which latrepirdine offers protection. This study investigates the effect of latrepirdine on Aβ aggregation, and presents evidence suggesting that caution should be applied in the use of thioflavin-T fluorescence based assays as a method for screening compounds for protein aggregation altering properties.

%B J Alzheimers Dis %V 50 %P 895-905 %8 2016 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/26836170?dopt=Abstract %R 10.3233/JAD-150790