Biomarkers.

Background: Younger-onset neurocognitive symptoms result from a heterogenous group of neurological and psychiatric disorders which present a diagnostic challenge. To identify such factors, we analysed the BeYOND (Biomarkers in Younger-Onset Neurocognitive Disorders) cohort, a study of individuals less than 65 years old presenting with neurocognitive symptoms for a clinical diagnosis and who have undergone cognitive and biomarker analyses.

Method: 65 participants were recruited during their index presentation to the Royal Melbourne Hospital Neuropsychiatry Centre, a tertiary specialist service in Melbourne, Australia.

Biomarkers.

Background: Diagnostic and prognostic decisions about Alzheimer's disease (AD) are more accurate when based on large data sets. We developed and validated a machine learning (ML) data harmonization tool for aggregation of prospective data from neuropsychological tests applied to study AD. The online ML-combine application (OML-combine app) allows researchers to utilize the ML-harmonization method for harmonization of their own data with that from other large available data bases (e.

Biomarkers.

Background: Alzheimer disease (AD) related cognitive decline occurs at relatively young ages in individuals with Down syndrome (DS, early-mid 50s) and in those with autosomal dominant mutations (ADAD, 40-50s). Both groups show similar patterns of amyloid accumulation. We examined if brain volumes are similarly affected by AD pathology in individuals with DS and ADAD.

Biomarkers.

Background: A growing body of research has confirmed the presence of epigenetic alterations in Alzheimer's disease (AD). While the causal relationship between these changes and AD remains uncertain, they offer a novel avenue to explore potential treatments. In this study, we aimed at characterising the methylation signatures of amyloid beta (Aβ) deposition, one of the main hallmarks of AD.

Biomarkers.

Background: Young-onset dementia (YOD) refers to the occurrence of dementia symptoms in people under the age of 65. Neuropsychiatric symptoms (NPS) are increasingly considered as the preclinical manifestations of YOD, posing a challenge to differentiate from psychiatric conditions with overlapping symptoms. The aim of this study is to investigate the AT(N), neuronal and glial pathologies underlying NPS and cognition in YOD.

Biomarkers.

Background: Plasma phospho-tau biomarkers, such as p217+tau, excel at identifying Alzheimer's Disease (AD) neuropathology. However, questions remain regarding their capacity to inform AD biological PET stages at group level and maintain the same precision at individual patient level.

Method: Participants included 248 cognitively unimpaired (CU) and 227 cognitively impaired (CI) individuals, with Janssen plasma p217+tau Simoa® assay, F-NAV4694 Aβ PET (A) and F-MK6240 tau PET (T) data.

Public Health.

Background: Accumulating evidence indicates exercise may delay or prevent the onset of Alzheimer's disease (AD). To our knowledge, no study has investigated the longitudinal impact of exercise on AD-related biomarkers in individuals with Autosomal dominant Alzheimer's disease (ADAD) mutations who are destined to develop AD. This study examined longitudinal associations between self-reported exercise levels and AD-related biomarkers in a cohort of ADAD mutation carriers and investigated whether observed associations depended upon disease stage.

Public Health.

Background: Lifestyle modifications incorporating a healthy diet, physical activity, brain training and health monitoring have proven effective in preventing dementia and related cognitive decline (REF). The Australian-Multidomain Lifestyle Intervention to reduce dementia risk (AU-ARROW) is an ongoing 2-yearintervention, which is the Australian contribution to the World-Wide FINGERS network. Here we report on preliminary findings of baseline dietary energy and nutrient intakes of AU-ARROW participants.

Public Health.

Background: Evidence suggests that diet may play a modifiable role in reducing Alzheimer's disease (AD) risk. Higher adherence to the Mediterranean diet (MeDi) is linked to a lower incidence of mild cognitive impairment (MCI) and AD. Increasing evidence indicates the potential utility of a cytoskeletal protein found in astrocytes, plasma Glial Fibrillary Acidic Protein (GFAP), as a marker specific for AD pathogenesis.

Public Health.

Background: Type 2 diabetes (T2D) and Alzheimer's disease (AD) are amongst the top 10 leading causes of death worldwide. T2D is associated with increased AD risk and brain beta amyloid (Aβ) burden, suggesting underlying mechanistic relationship between AD and T2D. Insulin signalling pathways, which can regulate the accumulation of Aβ and phosphorylation of tau in the brain, is a possible underlying mechanism of the T2D-AD relationship.

Public Health.

Background: Current literature focuses on the association between gut dysbiosis and the aggregation of Aβ, the development of tau protein, as well as neuroinflammation and oxidative stress associated with AD. Since the brain and gut are connected (gut-brain axis), gut microbiota and their metabolites may influence AD progression, or vice versa, if AD pathogenesis impacts the microbiome. Observational studies have shown an altered taxonomic composition of gut microbiota in AD patients compared to cognitively normal (CN) controls.

Biomarkers.

Background: As an extension of the central nervous system (CNS), the retina shares many similarities with the brain and can manifest signs of various neurological diseases, including Alzheimer's disease (AD). This study investigates the spectral features of the retina to develop a classification model for the differentiation of individuals with elevated brain amyloid levels.

Method: Participants (n=66) with varying brain Aβ levels, as determined by brain imaging, were non-invasively imaged using a hyperspectral retinal camera at wavelengths of 450 to 905 nm.

Biomarkers.

Background: Prediction of progression to Alzheimer's Disease Dementia (ADD) at the Mild Cognitive Impairment (MCI) stage is an unmet medical need. Mitochondrial dysfunction in Alzheimer's Disease at the brain and systemic level has been extensively described. Our previous studies showed an altered mtDNA methylation pattern throughout AD progression in human postmortem brains (Blanch et al.

Biomarkers.

Background: In early Alzheimer's disease (AD), amyloid-β (Aβ) accumulation is associated with volume loss in the basal forebrain (BF) and cognitive decline. However, the extent to which Aβ-related BF atrophy manifests as cognitive decline is not understood. This study sought to characterize the relationships between Aβ burden, BF atrophy, and the decline in memory and attention in older individuals without dementia.

Biomarkers.

Background: Epigenome-wide association studies (EWAS) have identified multiple loci that are differentially methylated in Alzheimer's disease (AD). However, for complex diseases such as AD, single methylation sites associated with disease and disease-related traits have relatively low effect sizes. At the genetic level, measures of cumulative genetic risk, such as polygenetic risk scores, have yielded success in risk prediction as well as in association and interaction studies.

Biomarkers.

Background: Recent advances in immunoassays have enabled sensitive detection of Aβ42/40 and pTau217 in plasma, components of Alzheimer's disease (AD) neuropathological markers. Further characterization of increased diagnostic accuracy with PET Amyloid-β (Aβ) across the AD continuum is needed for clinical application.

Method: Participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing (N=197) representing a cross-sectional population of four clinical and PET-Aβ subgroups: cognitive unimpaired (CU) Aβ- (n=75), CU Aβ+ (n=48), mild cognitive impairment (MCI) Aβ+ (n=26), and AD Aβ+ (n=48).

Biomarkers.

Background: Interplay between diet, depression, and Alzheimer's disease (AD) shows promise as an important area of study for early intervention and therapy. Associations between both depression and diet and heightened AD risk underscore the need to examine the moderating effect of dietary patterns on the relationship between depression, and AD-related blood-based biomarkers.

Method: Data from cognitively unimpaired older adults (n=89; age ≥60 years) enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study were included.

Biomarkers.

Background: Alzheimer's disease (AD) pathogenesis is not restricted to amyloid-beta, Aβ, and tau pathologies but involves dysregulation in diverse cellular and molecular processes. Numerous metabolomic studies revealed plasma metabolite alterations in AD individuals compared to healthy controls. Nevertheless, plasma P-tau181, an established biomarker for AD diagnosis and prognosis, has been described to reflect initial multiple cortical region Aβ deposition in cognitively intact adults.

Biomarkers.

Background: It is clinically a challenging task to accurately differentiate complex young-onset neurodegenerative disorders from psychiatric disorders which often present with similar neuropsychiatric symptoms (NPS) in their early stages. The aim of this study is to provide a more nuanced understanding of the interplay between NPS, cognition and multiple pathologies that may drive these disorders.

Method: This study was conducted at the Neuropsychiatry Centre, the Royal Melbourne Hospital, Melbourne, Australia, as part of a large, multi-site research study, the Markers in Neuropsychiatric Disorders Study.

Developing Topics.

Background: Worldwide, coffee and tea are two of the most popular beverages consumed. Studies have suggested a protective role of coffee and tea, including reduced risk of Alzheimer's disease. However, longitudinal data from large cohorts of older adults reporting associations of coffee and tea intake with cognitive decline is limited.

Alzheimer's Imaging Consortium.

Background: In early Alzheimer's disease (AD), amyloid-β (Aβ) accumulation is associated with volume loss in the basal forebrain (BF) and cognitive decline. However, the extent to which Aβ-related BF atrophy manifests as cognitive decline is not understood. This study sought to characterize the relationships between Aβ burden, BF atrophy, and the decline in memory and attention in older individuals without dementia.

Alzheimer's Imaging Consortium.

Background: Epigenome-wide association studies (EWAS) have identified multiple loci that are differentially methylated in Alzheimer's disease (AD). However, for complex diseases such as AD, single methylation sites associated with disease and disease-related traits have relatively low effect sizes. At the genetic level, measures of cumulative genetic risk, such as polygenetic risk scores, have yielded success in risk prediction as well as in association and interaction studies.

Alzheimer's Imaging Consortium.

Background: For large genomic studies of middle-aged individuals, the prevalence of Alzheimer's disease (AD) is extremely low, making it difficult to conduct genomic analysis of the condition. To enable genome-wide association studies of AD in such datasets, an approach called Genome-wide association by proxy (GWAX) uses family history of disease as a proxy for disease status. Borrowing from the machine learning (ML) literature, we treat the development of proxy phenotypes as a pseudo-labelling task, where an ideal proxy label accurately predicts the lifetime risk of AD.

Drug Development.

Background: The autophagy lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS) are key proteostasis mechanisms in cells, which are dysfunctional in AD and linked to protein aggregation and neuronal death. Autophagy is over activated in Alzheimer's disease brain whereas UPS is severely impaired. Activating autophagy has received most attention, however recent evidence suggests that UPS can clear aggregate proteins and a potential therapeutic target for AD and protein misfolding diseases.

Drug Development.

Background: Accumulation of amyloid beta 42 (Aβ42) senile plaques is the most critical event leading to Alzheimer's disease (AD). Currently approved drugs for AD have not been able to effectively modify the disease. This has caused increasing research interests in health beneficial nutritious plant foods as viable alternative therapy to prevent or manage AD.