In:
Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 99, No. 20 ( 2022-11-15), p. e2303-e2312
Abstract:
CSF biomarkers β‐amyloid 1-42 (Aβ 42 ), phosphorylated tau 181 (p-tau 181 ), total tau (t-tau), and neurogranin (Ng) can diagnose Alzheimer disease (AD) in life. However, it is unknown whether CSF concentrations, and thus their accuracies, are affected by concomitant pathologies common in AD, such as α-synuclein (αSyn). Our primary goal was to test whether biomarkers in patients with AD are altered by concomitant αSyn. We compared CSF Aβ 42 , p-tau 181 , t-tau, and Ng levels across autopsy-confirmed AD and concomitant AD and αSyn (AD + αSyn). Antemortem CSF levels were related to postmortem accumulations of αSyn. Finally, we tested how concommitant AD + αSyn affected the diagnostic accuracy of 2 CSF-based strategies: the amyloid/tau/neurodegeneration (ATN) framework and the t-tau/Aβ 42 ratio. Methods Inclusion criteria were neuropathologic diagnoses of AD, mixed AD + αSyn, and αSyn. A convenience sample of nonimpaired controls was selected with available CSF and a Mini-Mental State Examination (MMSE) ≥ 27. αSyn without AD and controls were included as reference groups. Analyses of covariance (ANCOVAs) tested planned comparisons were CSF Aβ 42 , p-tau 181 , t-tau, and Ng differences across AD and AD + αSyn. Linear models tested how biomarkers were altered by αSyn accumulation in AD, accounting for pathologic β-amyloid and tau. Receiver operating characteristic and area under the curve (AUC), including 95% CI, evaluated diagnostic accuracy. Results Participants were 61 patients with AD, 39 patients with mixed AD + αSyn, 20 patients with αSyn, and 61 controls. AD had similar median age (73 [interquartile range {IQR} = 12] years), MMSE (23 [IQR = 9] ), and sex distribution (male = 49%) compared with AD + αSyn age (70 [IQR = 13] years; p = 0.3), MMSE (25 [IQR = 9.5]; p = 0.19), and sex distribution (male = 69%; p = 0.077). ANCOVAs showed that AD + αSyn had lower p-tau 181 (F(1,94) = 17, p 〈 2.6e-16), t-tau (F(1,93) = 11, p = 0.0004), and Ng levels (F(1,50) = 12, p = 0.0004) than AD; there was no difference in Aβ 42 ( p = 0.44). Models showed increasing αSyn related to lower p-tau 181 (β = −0.26, SE = 0.092, p = 0.0065), t-tau (β = −0.19, SE = 0.092, p = 0.041), and Ng levels (β = −0.2, SE = 0.066, p = 0.0046); αSyn was not a significant factor for Aβ 42 ( p = 1). T-tau/Aβ 42 had the highest accuracy when detecting AD, including mixed AD + αSyn cases (AUC = 0.95; CI 0.92–0.98). Discussion Findings demonstrate that concomitant αSyn pathology in AD is associated with lower CSF p-tau 181 , t-tau, and Ng levels and can affect diagnostic accuracy in patients with AD.
Type of Medium:
Online Resource
ISSN:
0028-3878
,
1526-632X
DOI:
10.1212/WNL.0000000000201202
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2022
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