Potential Utility of Plasma Biomarker Panels in Differential Diagnosis of Alzheimer's Disease.

Blood tests are in need, in the clinical diagnosis of Alzheimer's disease (AD) as minimally invasive and less expensive alternatives to cerebrospinal fluid and neuroimaging methods. On these lines, single molecule array (Simoa) analysis of amyloid-β (Aβ), total tau (t-tau), phospho-tau (p-tau 181), and neurofilament L (NfL) in the plasma samples of AD subjects, healthy controls (HC), and non-AD subjects was conducted. Findings from this study suggest that a panel of multiple plasma biomarkers (NfL, Aβ, t-tau, and p-tau 181) combined with the clinical assessments could support differential diagnosis of AD and other dementias from healthy controls.

Pathological (Dis)Similarities in Neuronal Exosome-Derived Synaptic and Organellar Marker Levels Between Alzheimer's Disease and Frontotemporal Dementia.

Background: Alzheimer's disease (AD) and frontotemporal dementia (FTD) are pathologically distinct neurodegenerative disorders with certain overlap in cognitive and behavioral symptoms. Both AD and FTD are characterized by synaptic loss and accumulation of misfolded proteins, albeit, in different regions of the brain.

Objective: To investigate the synaptic and organellar markers in AD and FTD through assessment of the levels of synaptic protein, neurogranin (Ng) and organellar proteins, mitofusin-2 (MFN-2), lysosomal associated membrane protein-2 (LAMP-2), and golgin A4 from neuronal exosomes.

Plasma neurofilament L to amyloid β42 ratio in differentiating Alzheimer's type from non-Alzheimer's dementia: A cross-sectional pilot study from India.

Based on the reduction of amyloid β plaques, US FDA has recently approved Aducanumab as a disease modifying treatment for Alzheimer's disease (AD). With high pricing and the potential risks likely with this treatment, certainty of AD diagnosis becomes crucial. The current pilot study evaluated plasma levels of neurofilament L, an axonal injury marker and amyloid β42, a major component of amyloid plaques for discriminating AD from non-AD dementia (NAD).

Increased prolidase activity in Alzheimer's dementia: A case-control study.

Prolidase enzyme, which catalyzes the final step in collagen metabolism can influence the cognitive functions through changes in extracellular matrix (ECM) resulting in altered synaptic connectivity in Alzheimer's disease (AD). In this study, it was found that the prolidase activity was significantly higher (p = 0.0016) in AD subjects (5.

Elevated serum adenosine deaminase levels in neuroleptic-naïve patients with recent-onset schizophrenia.

The present study examined serum levels of adenosine deaminase (ADA), an adenosine metabolizing enzyme, in neuroleptic-naive patients with recent-onset schizophrenia and age-matched healthy comparison subjects. ADA levels were found to be higher among patients, and revealed a possible link between evening rise and severity of auditory hallucinations as well as morning rise and severity of avolition-apathy in patients with schizophrenia. These findings suggest the potential utility of serum ADA as a peripheral biomarker of schizophrenia.

Passive immunization targeting the N-terminal region of phosphorylated tau (residues 68-71) improves spatial memory in okadaic acid induced tauopathy model rats.

Alzheimer's disease (AD) is the leading cause of dementia, characterized by progressive loss of memory and other cognitive functions. The cognitive impairment in patients with AD is closely associated with loss of synapses and the formation of neurofibrillary tangles (NFT) containing hyperphosphorylated tau in the hippocampus. Effective treatment for AD is still not available.

Cognition enhancing effect of the aqueous extract of Cinnamomum zeylanicum on non-transgenic Alzheimer's disease rat model: Biochemical, histological, and behavioural studies.

Objective: Several dietary supplements are actively being tested for their dual role of alleviating the metabolic perturbations and restricting the consequent cognitive dysfunctions seen in neurodegenerative disorders such as Alzheimer's disease (AD). The aim of the current study was to assess the influence of aqueous extract of cinnamon (CE) on the monosodium glutamate-induced non-transgenic rat model of AD (NTAD) established with insulin resistance, hyperglycaemia, neuronal loss, and cognitive impairment at a very early stage of life.

Methods: The experimental design included oral administration of CE (50 mg/kg body weight) for 20 weeks to 2-month and 10-month-old NTAD rats.

Development of a dot blot assay with antibodies to recombinant "core" 14-3-3 protein: Evaluation of its usefulness in diagnosis of Creutzfeldt-Jakob disease.

Background And Purpose: Definitive diagnosis of Creutzfeldt-Jakob disease (CJD) requires demonstration of infective prion protein (PrP(Sc)) in brain tissues by immunohistochemistry or immunoblot, making antemortem diagnosis of CJD difficult. The World Health Organization (WHO) recommends detection of 14-3-3 protein in cerebrospinal fluid (CSF) in cases of dementia, with clinical correlation, as a useful diagnostic marker for CJD, obviating the need for brain biopsy. This facility is currently available in only a few specialized centers in the West and no commercial kit is available for clinical diagnostic use in India.

The Neuroprotective Effect of Dark Chocolate in Monosodium Glutamate-Induced Nontransgenic Alzheimer Disease Model Rats: Biochemical, Behavioral, and Histological Studies.

The vulnerability to oxidative stress and cognitive decline continue to increase during both normal and pathological aging. Dietary changes and sedentary life style resulting in mid-life obesity and type 2 diabetes, if left uncorrected, further add to the risk of cognitive decline and Alzheimer disease (AD) in the later stages of life. Certain antioxidant agents such as dietary polyphenols, taken in adequate quantities, have been suggested to improve the cognitive processes.

Combination of Spirulina with glycyrrhizin prevents cognitive dysfunction in aged obese rats.

Objectives: To evaluate the cognition enhancing effect of the combination of Spirulina and glycyrrhizin in monosodium glutamate (MSG)-induced obese aged rats.

Materials And Methods: Obesity was induced in rats by administration of MSG (intraperitoneally, 4 mg/g body weight) for 14 consecutive days from day 1 after birth. Subsequently, the animals were allowed to grow for 18 months with food and water ad libitum.

Supportive CSF biomarker evidence to enhance the National Institute on Aging-Alzheimer's Association criteria for diagnosis of Alzheimer's type dementia--a study from Southern India.

The present study was undertaken to validate the measurement of biomarkers as a supplement to the latest diagnostic criteria for Alzheimer disease (AD) dementia by National Institute on Aging-Alzheimer's Association (NIA-AA) work group using a sample attending a tertiary care center in Southern India. A total of 20 subjects diagnosed clinically as Alzheimer's dementia according to the NIA-AA criteria for AD were included in the study. The CSF biomarkers Aβ42, t-tau, and p-tau181 were assessed.

Amyloid beta lowering and cognition enhancing effects of ghrelin receptor analog [D-Lys (3)] GHRP-6 in rat model of obesity.

Obesity arising due to the dietary and life style changes is fast reaching epidemic proportions all over the world. There is increasing evidence that the incidence of Alzheimer disease (AD) is significantly influenced by a cluster of metabolic diseases, including diabetes and obesity. This study was aimed to test the suitability of experimentally-induced obesity in rats as an experimental animal model of AD.

In vitro evaluation of anti-Alzheimer effects of dry ginger (Zingiber officinale Roscoe) extract.

As the disease modifying therapies against Alzheimer's disease (AD) continue to exist as a major challenge of this century, the search for newer drug leads with lesser side effects is on the rise. A large number of plant extracts and phytocompounds are being actively pursued for their anti-Alzheimer effects. In the present study, the antioxidant activity, cholinesterase inhibition, anti-amyloidogenic potential and neuroprotective properties of methanolic extract of dry ginger (GE) have been evaluated.

In vitro screening for anti-cholinesterase and antioxidant activity of methanolic extracts of ayurvedic medicinal plants used for cognitive disorders.

Inhibition of Acetylcholinesterase (AChE) is still considered as the main therapeutic strategy against Alzheimer's disease (AD). Many plant derived phytochemicals have shown AChE inhibitory activity in addition to the currently approved drugs for AD. In the present study, methanolic extracts of 20 plants used in Indian Ayurvedic system of medicine for improving cognitive function were screened for acetylcholinesterase inhibitory activity by Ellman's microplate colorimetric method.

Intranasal administration of insulin lowers amyloid-beta levels in rat model of diabetes.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by abnormal accumulation of amyloid beta (A beta) peptide in brain regions subserving memory and other cognitive functions. Hyperglycemia and perturbed insulin signaling have been proposed as pathogenic factors contributing to AD. The aim of the present study is to validate the use of streptozotocin (STZ) injected rats as an experimental model of AD.

Identification and mapping of linear antigenic determinants of human amyloid ß(1-42) peptide.

Accumulation of cytotoxic oligomers of amyloid ß (Aß) is one of the major pathological hallmarks of Alzheimer's disease (AD). Several immunological approaches that prevent the conversion of Aß into its toxic form or that accelerate its clearance are being actively pursued worldwide. As part of these attempts, we have carried out sequential epitope analysis of Aß where antibodies raised against native Aß and its homologue Aß-KEK were screened for binding to five overlapping hexadecapeptides encompassing the full length of Aß sequence with 10 amino acid overlap.

I32E and V36K double mutation in beta2-sheet abrogates amyloid beta peptide toxicity.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, wherein, the accumulation of amyloid beta (Abeta) peptide as cytotoxic oligomers leads to neuropathologic changes. Transgenic mice with brain Abeta plaques immunized with aggregated Abeta have reduced amyloid burden and improved cognitive functions. However, such active immunization in humans led to a small but significant occurrence of meningoencephalitis in 6% AD volunteers due to Abeta induced toxicity.

Design and development of non-fibrillar amyloid beta as a potential Alzheimer vaccine.

Alzheimer's disease (AD) is the most common cause of dementia affecting the elderly. Treatment for effective cure of this complex neurodegenerative disease does not yet exist. In AD, otherwise soluble, monomeric form of amyloid beta (Abeta) peptide converts into toxic, fibrillar form rich in beta-sheet content.

Influence of conformational antibodies on dissociation of fibrillar amyloid beta (A beta 1-42) in vitro.

Many neurodegenerative diseases result due to the accumulation of misfolded proteins as amyloid fibrils. Although the protein components of these fibrils from different disease states differ considerably, they appear to share common structure. Among these conformational disorders, Alzheimer's disease (AD) and prion diseases exhibit significant overlap in their mechanism of pathogenesis.

Enhanced Th2 immunity after DNA prime-protein boost immunization with amyloid beta (1-42) plus CpG oligodeoxynucleotides in aged rats.

Generation and accumulation of fibrillar amyloid beta (Abeta) is widely considered as the pathogenic basis of neurodegeneration in Alzheimer's disease (AD). Both active immunization with fibrillar Abeta and passive immunization with anti-Abeta antibodies in transgenic mouse models of AD result in prevention/dissociation of Abeta plaque formation and restoration of cognitive functions. However, similar immunization studies in humans had to be halted because 6% of the AD patients developed acute meningoencephalitis, likely due to anti-Abeta specific autoimmune Th1 cells.

Expression, purification and characterization of a synthetic gene encoding human amyloid beta (Abeta1-42) in Escherichia coli.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive loss of cognitive function. Existing evidence indicates that abnormal processing and extracellular deposition of the longer form of the amyloid peptide Abeta(1-42), a proteolytic derivative of the amyloid precursor protein (APP), is a key step in the pathogenesis of AD. Active immunization with Abeta(1-42) has been shown to decrease brain beta deposition and improve cognitive performance in mouse models of AD.