Multiplexed assay and methods of use thereof
A subject, amyloidosis technology, used in applications, measurement devices, biological tests, etc.
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Embodiment 1
[0090] A non-invasive, inexpensive Alzheimer's disease (AD) screening test is needed to advance clinical and prevention trials. A sensitive and specific immunoprecipitation mass spectrometry (IPMS) blood test for the amyloid-beta (Aβ) peptides Aβ42 and Aβ40 has been developed. A[beta]42 / A[beta]40 measured by IPMS was significantly lower in amyloid PET-positive individuals compared to amyloid PET-negative individuals in multiple cohorts. A logistic regression model predicting amyloid PET status by plasma Aβ42 / Aβ40 had a ROC AUC of 0.88, which increased to 0.95 when ApoE ε4 status and age were included in the model. A single measurement of plasma Aβ42 / Aβ40 and ApoE ε4 status would reduce screening costs for recruiting participants to AD drug trials and could potentially be used for clinical diagnosis.
[0091] A pilot study (n = 41 subjects, >500 samples) quantified plasma Aβ42 and Aβ40 in plasma and found higher levels in amyloid PET-positive individuals compared to amyloid PE...
Embodiment 2
[0095] Participants in the Memory and Aging Study at Washington University were included if they had had plasma collection within 18 months of the amyloid PET scan. Because the assay used 1.6 ml plasma, samples for which enough plasma was available in the biobank were selected. Participants of all ages and diagnoses were included, but biobanks obtained more plasma from younger and cognitively normal participants. Therefore, this cohort represents a convenience sample. All participants underwent a clinical assessment, including the Clinical Dementia Rating (CDR) 14 and Mentally Handicapped Status Examination (MMSE) 15 . APOE Genotypes were obtained from Knight ADRC Genetics Core 16 . All procedures were approved by the Washington University Human Research Protection Office and written informed consent was obtained from each participant.
[0096] Collect CSF as previously described 17 . Participants received LP at 8 am after an overnight fast. Collect 20 to 30 ml of CS...
Embodiment 3
[0173] Current clinical diagnosis of Alzheimer's disease (AD) relies on progressive memory decline and cognitive impairment due to a lack of specific, simple and inexpensive tests. However, clinical diagnosis has poor sensitivity and specificity for AD and other neurodegenerative dementias. Diagnostic tests currently in development include CSF and PET scans for tau tangles and amyloid-plaque pathology. However, these protocols are invasive, require extensive training, and are expensive. Furthermore, early asymptomatic detection of AD pathology is essential for enrolling participants in research studies, clinical trials and prevention trials.
[0174] Blood tests used to improve clinical diagnosis and accelerate therapeutic development need to have improved specificity and sensitivity in participants ranging from normal to cognitively impaired, be minimally invasive, and inexpensive. In addition, the assay should include measurements of key areas of AD: genetic risk (ApoE), p...
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