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P2‐163: Performance Evaluation of New Absorbance‐Based Elisas for Measuring Different Alpha‐Synuclein (A‐SYN) Species in CSF and Plasma
Author(s) -
Stoops Erik,
Majbour Nour,
Mauroo Kimberley,
Demeyer Leentje,
Lashuel Hilal,
Trojanowski John Q.,
M-Y Lee Virginia,
El Agnaf Omar,
Vanderstichele Hugo Marcel
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.1330
Subject(s) - gene isoform , monoclonal antibody , chemistry , monomer , synucleinopathies , alpha synuclein , epitope , absorbance , oligomer , computational biology , antibody , microbiology and biotechnology , chromatography , biochemistry , biology , parkinson's disease , immunology , medicine , disease , polymer , organic chemistry , pathology , gene
75% sensitivity and 79% specificity in accurately categorizing an older adult’s Ab+/status (positive predictive value1⁄461%, negative predictive value1⁄487%, Diagnostic Odds Ratio (DOR)1⁄411, accuracy1⁄477%; Figure 2-3). Providing context, this discrimination accuracy mirrored that observed with APOE genotype (DOR1⁄412, accuracy1⁄477%), a known Ab risk factor. Importantly, <1Hz NREM SWA accurately predicted Ab+/status even when controlling for age and gender (logistic regression; P1⁄40.012). Moreover, lower<1Hz NREM SWA increased Ab+ risk by 30%, while higher <1Hz NREM SWA reduced risk by 27%, also similar to APOE genotype. Finally,<1Hz NREM SWA not only predicted the severity of Ab burden at baseline (r1⁄4-0.69, P1⁄40.009), but also 3-5 years later (r1⁄4-0.68, P1⁄40.011), with a trend for predicting the 3-5 year change in Ab accumulation (r1⁄4-0.41, one-tailed P1⁄40.084; Figure 4). Conclusions: These data support the potential utility of <1Hz NREM SWA as a novel surrogate biomarker of Ab pathology, one that is non-invasive, safe, inexpensive, and suitable for ADrisk screening within the broader community setting, even before onset of clinical symptoms. Furthermore, this AD biomarker is predictive, heralding Ab burden years later, underscoring the benefit of greater clinician sensitivity to sleep disruption as a predisposing AD-risk factor. While clinically promising, improved precision is needed, potentially including additional sleep measures and/or other non-invasive biomarker candidates.