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. 2024 Dec 20;12(12):2904.
doi: 10.3390/biomedicines12122904.

Cerebrospinal Fluid Classical Biomarker Levels in Mixed vs. Pure A+T+ (A+T1+) Alzheimer's Disease

Ioanna Tsantzali  1 , Athanasia Athanasaki  1 , Fotini Boufidou  2 , Vasilios C Constantinides  2 , Maria-Ioanna Stefanou  1 , Christos Moschovos  1 , Christina Zompola  1 , Sotirios G Paraskevas  1 , Anastasios Bonakis  1 , Sotirios Giannopoulos  1 , Georgios Tsivgoulis  1   3 , Elisabeth Kapaki  2 , George P Paraskevas  1   2
Affiliations

Cerebrospinal Fluid Classical Biomarker Levels in Mixed vs. Pure A+T+ (A+T1+) Alzheimer's Disease

Ioanna Tsantzali et al. Biomedicines. .

Abstract

Background: Alzheimer's disease (AD) may present with pure (typical or atypical) and mixed phenotypes, sometimes causing difficulties in (differential) diagnosis. In order to achieve a diagnostic accuracy as high as possible, the diagnosis of AD during life depends on various biomarkers, including the cerebrospinal fluid (CSF) biomarkers. Methods: Classical CSF AD biomarkers were determined in a total of 61 patients, classified as both beta amyloid- and tau-positive A+T+ (or A+T1+ according to the recently revised Alzheimer Association criteria for diagnosis and staging of AD). Twenty one of these patients fulfilled the criteria for mixed AD (mixed with Lewy bodies, cerebrovascular disease, or normal pressure hydrocephalus), whilst 40 had pure AD. Results: Patients did not differ with respect to gender, education, disease duration, and cognitive status. After controlling for confounding factors, no difference was observed between mixed and pure AD groups in Aβ42 or Aβ42/Aβ40 levels. Although by definition, patients of both groups had abnormal (increased) levels of phospho-tau181, the mixed AD group presented with lower (less abnormal) levels of phospho-tau181 and total tau as compared to the pure group. Conclusions: In patients with AD of comparable cognitive status, mixed AD cases may present with lower levels of tau proteins and, if close to the cut-off values, diagnostic uncertainty may be increased.

Keywords: Alzheimer’s disease; beta amyloid; biomarkers; cerebrospinal fluid; phospho-tau; tau protein.

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Conflict of interest statement

G.T., G.P.P., I.T, A.A., C.Z. and A.B. are clinical investigators in the “EVOKE” and “EVOKE plus” trials of semaglutide for early Alzheimer’s disease (NovoNordisk, NCT04777396, and NCT04777409 respectively). G.P.P received fees from Biogen International and from ITF Hellas, as a consultant of advisory boards. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Flow chart of the participants included in the present study.
Figure 2
Figure 2
Scatterplot of CSF biomarker levels. Error bars for (a–c) indicate mean ± standard deviation. Error bars for (d,e) indicate median with interquartile range. Broken lines indicate cut-off values of our laboratory.
Figure 3
Figure 3
Negative correlation between the Aβ42/Aβ40 ratio and the CSF levels of τP-181 (a) or τT (b).
See this image and copyright information in PMC

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