Saliva Proteome, Metabolome and Microbiome Signatures for Detection of Alzheimer's Disease.

As the burden of Alzheimer's disease (AD) escalates with an ageing population, the demand for early and accessible diagnostic methods becomes increasingly urgent. Saliva, with its non-invasive and cost-effective nature, presents a promising alternative to cerebrospinal fluid and plasma for biomarker discovery. : In this study, we conducted a comprehensive multi-omics analysis of saliva samples ( = 20 mild cognitive impairment (MCI), = 20 Alzheimer's disease and age- and = 40 gender-matched cognitively normal individuals), from the South Australian Neurodegenerative Disease (SAND) cohort, integrating proteomics, metabolomics, and microbiome data with plasma measurements, including pTau181.

Salivary inflammatory biomarkers are predictive of mild cognitive impairment and Alzheimer's disease in a feasibility study.

Alzheimer's disease (AD) is an insidious disease. Its distinctive pathology forms over a considerable length of time without symptoms. There is a need to detect this disease, before even subtle changes occur in cognition.

Multi-Omics, an Integrated Approach to Identify Novel Blood Biomarkers of Alzheimer's Disease.

The metabolomic and proteomic basis of mild cognitive impairment (MCI) and Alzheimer's disease (AD) is poorly understood, and the relationships between systemic abnormalities in metabolism and AD/MCI pathogenesis is unclear. This study compared the metabolomic and proteomic signature of plasma from cognitively normal (CN) and dementia patients diagnosed with MCI or AD, to identify specific cellular pathways and new biomarkers altered with the progression of the disease. We analysed 80 plasma samples from individuals with MCI or AD, as well as age- and gender-matched CN individuals, by utilising mass spectrometry methods and data analyses that included combined pathway analysis and model predictions.

Salivaomics as a Potential Tool for Predicting Alzheimer's Disease During the Early Stages of Neurodegeneration.

Background: The metabolomic and proteomic basis of mild cognitive impairment (MCI) and Alzheimer's disease (AD) is poorly understood and the relationships between systemic abnormalities in metabolism and AD/AMCI pathogenesis are unclear.

Objective: The aim of the study was to compare the metabolomic and proteomic signature of saliva from cognitively normal and patients diagnosed with MCI or AD, to identify specific cellular pathways altered with the progression of the disease.

Methods: We analyzed 80 saliva samples from individuals with MCI or AD as well as age- and gender-matched healthy controls.

CYLD is a causative gene for frontotemporal dementia - amyotrophic lateral sclerosis.

Frontotemporal dementia and amyotrophic lateral sclerosis are clinically and pathologically overlapping disorders with shared genetic causes. We previously identified a disease locus on chromosome 16p12.1-q12.

γH2AX is increased in peripheral blood lymphocytes of Alzheimer's disease patients in the South Australian Neurodegeneration, Nutrition and DNA Damage (SAND) study of aging.

An early cellular response to DNA double-strand breaks is the phosphorylation of histone H2AX to form γH2AX. Although increased levels of γH2AX have been reported in neuronal nuclei of Alzheimer's disease (AD) patients, γH2AX responses in the lymphocytes of individuals with mild cognitive impairment (MCI) and AD remain unexplored. In this study, the endogenous γH2AX level was measured, using laser scanning cytometry (LSC) and visual scoring, in lymphocyte nuclei from MCI (n = 18), or AD (n = 20) patients and healthy controls (n = 40).

Guanine-quadruplexes are increased in mild cognitive impairment and correlate with cognitive function and chromosomal DNA damage.

Guanine-quadruplexes (G4) are highly stable DNA secondary structures known to mediate gene regulation and to trigger genomic instability events during replication. G4 are known to be associated with DNA damage and we propose that G4 are involved in the ageing disorder mild cognitive impairment (MCI). Lymphocytes were obtained from healthy controls and individuals with MCI.

Chromosomal DNA damage measured using the cytokinesis-block micronucleus cytome assay is significantly associated with cognitive impairment in South Australians.

Loss of genome integrity may be associated with increased risk for neurodegenerative disease. The aim of this study was to investigate whether mild cognitive impairment (MCI) or Alzheimer's disease (AD) individuals have increased DNA damage relative to age- and gender- matched controls using the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. DNA damage was measured as micronuclei (MN), nucleoplasmic bridges (NPB), and nuclear buds (NBUD) in binucleated cells.

Altered cytological parameters in buccal cells from individuals with mild cognitive impairment and Alzheimer's disease.

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.

Frontotemporal dementia-amyotrophic lateral sclerosis syndrome locus on chromosome 16p12.1-q12.2: genetic, clinical and neuropathological analysis.

Numerous families exhibiting both frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) have been described, and although many of these have been shown to harbour a repeat expansion in C9ORF72, several C9ORF72-negative FTD-ALS families remain. We performed neuropathological and genetic analysis of a large European Australian kindred (Aus-12) with autosomal dominant inheritance of dementia and/or ALS. Affected Aus-12 members developed either ALS or dementia; some of those with dementia also had ALS and/or extrapyramidal features.

The long-term efficacy and tolerability of donepezil in patients with vascular dementia.

Objective: To determine the long-term tolerability and efficacy of donepezil in patients with vascular dementia (VaD).

Methods: International, multicentre, open-label, 30-week extension study of two 24-week, randomised, double-blind, placebo-controlled studies. Participants were ambulatory adults (59% female; mean age, 74.

Pedigree with frontotemporal lobar degeneration--motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9.

Background: Frontotemporal lobar degeneration (FTLD) represents a clinically, pathologically and genetically heterogenous neurodegenerative disorder, often complicated by neurological signs such as motor neuron-related limb weakness, spasticity and paralysis, parkinsonism and gait disturbances. Linkage to chromosome 9p had been reported for pedigrees with the neurodegenerative disorder, frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND). The objective in this study is to identify the genetic locus in a multi-generational Australian family with FTLD-MND.

Buccal micronucleus cytome biomarkers may be associated with Alzheimer's disease.

Alzheimer's disease (AD) is a progressive degenerative disorder of the brain and is the commonest form of dementia. A buccal cytome assay was used to measure ratios of buccal cell populations and micronuclei in clinically diagnosed Alzheimer's patients compared to age and gender-matched controls. Frequencies of basal cells (P < 0.

Environmental stress, psychological stress and allostatic load.

The mechanism by which chronic caregiving stress results in poor health is not well understood. The objective was to determine whether such a mechanism may be allostatic load, a novel concept specifying physiological systems that may suffer cumulative wear and tear following chronic stress, leading collectively to poor health. The study examines the association of allostatic load with environmental and psychological stress in the contexts of dementia caregiving and relinquishment of care, and is a 2-year longitudinal comparison of three groups: 80 new dementia spouse caregivers, 120 veteran caregivers, and 60 non-caregivers.

Efficacy and safety of donepezil in patients with more severe Alzheimer's disease: a subgroup analysis from a randomized, placebo-controlled trial.

Background: There have been very limited investigations of cholinesterase inhibitor therapy in more advanced stages of Alzheimer's disease (AD). The efficacy and safety of donepezil were evaluated in post hoc analyses of a subgroup of patients with more severe AD (standardized Mini-Mental State Examination [sMMSE] score 5-12) within a randomized, placebo-controlled trial in moderate to severe AD (MSAD study). Additional analyses examined whether donepezil's treatment effects were consistent across the full range of baseline AD severity studied (sMMSE score 5-17).

Efficacy and tolerability of donepezil in vascular dementia: positive results of a 24-week, multicenter, international, randomized, placebo-controlled clinical trial.

Background And Purpose: Clinical observations suggest that patients with vascular dementia (VaD) may benefit from treatment with cholinesterase inhibitors. This study evaluated the efficacy and safety of donepezil for relieving symptoms of dementia in VaD.

Methods: Patients (n=603; mean age, 73.

Efficacy of donepezil on maintenance of activities of daily living in patients with moderate to severe Alzheimer's disease and the effect on caregiver burden.

Objectives: This study investigated the efficacy of donepezil treatment on activities of daily living (ADLs) and social functioning in patients with moderate to severe Alzheimer's disease (AD) and the possible benefits of this treatment on caregiving time and stress levels.

Design: Randomized, double-blind, placebo-controlled, multinational study.

Setting: Patients resided in the community or in assisted living facilities who did not require skilled 24-hour nursing care.

Efficacy of donepezil on behavioral symptoms in patients with moderate to severe Alzheimer's disease.

Objective: This subanalysis of a large, double-blind, placebo-controlled trial examined the prevalence of behavioral symptoms in moderate to severe Alzheimer's disease (AD), and the effect of treatment with donepezil.

Methods: Two hundred ninety patients with moderate to severe AD (standardized Mini-Mental State Examination scores 5-17) were randomized to receive 24 weeks of once-daily doses of donepezil 5 mg/day for 28 days, and 10 mg/day thereafter per the clinician's judgment (n = 144), or placebo (n = 146). The outcome measure of interest was the 12-item Neuropsychiatric Inventory (NPI).