Alzheimer's Disease (AD) biomarker measurement is key to aid in the diagnosis and prognosis of the disease. In the research setting, participant recruitment and retention and optimization of sample use, is one of the main challenges that observational studies face. Thus, obtaining accurate established biomarker measurements for stratification and maximizing use of the precious samples is key. Accurate technologies are currently available for established biomarkers, mainly immunoassays and immunoprecipitation liquid chromatography-mass spectrometry (IP-MS), and some of them are already being used in clinical settings. Although some immunoassays- and IP-MS based platforms provide multiplexing for several different coding proteins there is not a current platform that can measure all the stablished and emerging biomarkers in one run. The NUcleic acid Linked Immuno-Sandwich Assay (NULISA) is a mid-throughput platform with antibody-based measurements with a sequencing output that requires 15μL of sample volume to measure more than 100 analytes, including those typically assayed for AD. Here we benchmarked and compared the AD-relevant biomarkers including in the NULISA against validated assays, in both CSF and plasma. Overall, we have found that CSF measures of Aß42/40, NfL, GFAP, and p-tau217 are highly correlated and have similar predictive performance when measured by immunoassay, mass-spectrometry or NULISA. In plasma, p-tau217 shows a performance similar to that reported with other technologies when predicting amyloidosis. Other established and exploratory biomarkers (total tau, p-tau181, NRGN, YKL40, sTREM2, VILIP1 among other) show a wide range of correlation values depending on the fluid and the platform. Our results indicate that the multiplexed immunoassay platform produces reliable results for established biomarkers in CSF that are useful in research settings, with the advantage of measuring additional novel biomarkers using minimal sample volume.
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http://dx.doi.org/10.1101/2024.06.13.24308895 | DOI Listing |
Alzheimers Res Ther
January 2025
Department of Neurology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan.
Background: Intracerebral amyloid β (Aβ) accumulation is considered the initial observable event in the pathological process of Alzheimer's disease (AD). Efficient screening for amyloid pathology is critical for identifying patients for early treatment. This study developed machine learning models to classify positron emission tomography (PET) Aβ-positivity in participants with preclinical and prodromal AD using data accessible to primary care physicians.
View Article and Find Full Text PDFFluids Barriers CNS
January 2025
Neurology 5 - Neuropathology Unit, Fondazione IRCCS - Istituto Neurologico Carlo Besta, Via Celoria 11, Milan, 20133, Italy.
Background: The approval of new disease-modifying therapies by the U.S. Food and Drug Administration and the European Medicine Agency makes it necessary to optimize non-invasive and cost-effective tools for the identification of subjects at-risk of developing Alzheimer's Disease (AD).
View Article and Find Full Text PDFNeurol Sci
January 2025
School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder ranging from mild cognitive impairment (MCI) to AD dementia. Abnormal cerebral perfusion alterations, influenced by amyloid-beta (Aβ) accumulations, have been implicated in cognitive decline along this spectrum.
Objective: This study investigates the relationship between cerebrospinal fluid (CSF) Aβ1-42 levels and regional cerebral blood flow (CBF) changes across the AD continuum using the Arterial Spin Labeling (ASL) technique.
Mol Divers
January 2025
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, 116024, Liaoning, China.
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases. Given the multifactorial pathophysiology of AD, monotargeted agents can only alleviate symptoms but not cure AD. Acetylcholinesterase (AChE) and Monoamine oxidase B (MAO-B) are two key targets in the treatment of AD, molecules that inhibiting both targets are considered promising avenue to develop more effective AD therapies.
View Article and Find Full Text PDFDrugs Aging
January 2025
The Dementia Centre, HammondCare, St Leonards, NSW, Australia.
Background And Objectives: Despite their limited benefits and serious adverse effects, psychotropics remain frequently prescribed for neuropsychiatric symptoms (NPS) of dementia. Psychotropic polypharmacy, the use of two or more concomitant psychotropic medications, is therefore not recommended for people with dementia. The objectives of this study were to investigate the prevalence of psychotropic polypharmacy in Australians living with dementia whose caregivers sought external NPS support from Dementia Support Australia (DSA; the national provider of NPS support) and the association of psychotropic polypharmacy with their demographics and NPS characteristics.
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