Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May 22;80(4):36399.
doi: 10.31083/RN36399.

[Cerebrospinal Fluid Biomarker Profile in Atypical Alzheimer's Disease]

[Article in Spanish]
Elisa Martínez Campos  1 , Paula Tellechea Aramburo  1 , Javier Sánchez Ruiz de Gordoa  1 , Rosa Larumbe Ilundain  1
Affiliations

[Cerebrospinal Fluid Biomarker Profile in Atypical Alzheimer's Disease]

[Article in Spanish]
Elisa Martínez Campos et al. Rev Neurol. .

Abstract
in English, Spanish

Introduction: Cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) are essential for the early identification of non-amnestic phenotypes. Increased levels of total tau (t-tau) and phosphorylated tau (p-tau) have been reported in atypical AD cases, although the specific pattern remains a subject of debate. This study aimed to evaluate CSF biomarker profiles in relation to clinical phenotype.

Materials and methods: A retrospective review was performed, analyzing demographic data, time to diagnosis, clinical phenotype, and core AD biomarkers (beta-amyloid peptide 1-42 (Aβ1-42), t-tau, p-tau) in CSF from patients evaluated at University Hospital in Navarra between 2019 and 2022.

Results: The study included 57 patients (54% female, mean age 67 years), of whom 41 met AD diagnostic criteria. Among these, 10 patients (25%) presented with atypical phenotypes (50% aphasic, 30% frontal, 20% mixed non-amnestic). Compared with the amnestic phenotype, the atypical group exhibited significantly higher t-tau (562.9 pg/mL vs 320.3 pg/mL, p = 0.021) and p-tau (81.5 pg/mL vs 37.7 pg/mL, p = 0.016) levels, independent of age, sex, and time to diagnosis.

Conclusions: Atypical cases demonstrated increased tau levels, suggesting earlier and more extensive cortical damage than the amnestic phenotype. These findings underscore the significance of CSF biomarkers in phenotypic differentiation, disease course prediction, and individualized treatment strategies for AD.

Introducción: Los biomarcadores de la Enfermedad de Alzheimer (EA) en líquido cefalorraquídeo (LCR) tienen un papel significativo en el diagnóstico precoz de fenotipos no-amnésicos. Se han descrito mayores niveles de tau total (t-tau) y tau fosforilada (p-tau) en casos atípicos de EA, aunque la existencia de un patrón diferencial sigue siendo controvertida. Nuestro objetivo fue estudiar las diferencias en el perfil de biomarcadores de EA en LCR en función del fenotipo. Material y Métodos: Revisión retrospectiva de características demográficas, tiempo hasta el diagnóstico, fenotipo clínico y biomarcadores “core” (péptido beta-amiloide 1-42 (Aβ1-42), t-tau, p-tau) de EA en LCR de pacientes valorados en nuestro centro entre 2019–2022. Resultados: 57 fueron pacientes analizados (54% mujeres, edad media 67 años). 41 cumplían criterios diagnósticos de EA. De ellos, 10 (25%) presentaron un perfil atípico (50% afásico, 30% frontal, 20% mixto no amnésico). El grupo atípico presentó niveles mayores de t-tau (562,9 pg/mL vs 320,3 pg/mL, p = 0,021) y p-tau (81,5 pg/mL vs 37,7 pg/mL, p = 0,016) respecto al fenotipo amnésico, independientemente de la edad, sexo y tiempo hasta el diagnóstico. Conclusiones: En nuestro estudio, los casos atípicos presentaron valores de tau más elevados. Dichos resultados apoyan que estos fenotipos presentan daño cortical más precoz y grave que el fenotipo amnésico y subrayan la importancia de los biomarcadores en LCR como herramienta para la estratificación, predicción del curso clínico y personalización terapéutica de nuestros pacientes.

Keywords: Alzheimer-type dementia (ATD); Alzheimer’s disease, early onset; aphasia, primary progressive; cerebrospinal fluid; tau proteins.

PubMed Disclaimer

Conflict of interest statement

Los autores declaran no tener conflictos de interés.

Figures

Fig. 1.
Fig. 1.
Porcentaje de pacientes con EA confirmada por biomarcadores clasificados en los diferentes fenotipos en función de la clínica inicial y estudio neuropsicológico. EA, enfermedad de Alzheimer.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Bloom GS. Amyloid-β and tau: the trigger and bullet in Alzheimer disease pathogenesis. JAMA Neurology . 2014;71:505–508. doi: 10.1001/jamaneurol.2013.5847. - DOI - PubMed
    1. Jones D, Pelak V, Rogalski E. Atypical Presentations of Alzheimer Disease. Continuum (Minneapolis, Minn.) . 2024;30:1614–1641. doi: 10.1212/CON.0000000000001504. - DOI - PubMed
    1. Ossenkoppele R, Schonhaut DR, Schöll M, Lockhart SN, Ayakta N, Baker SL, et al. Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease. Brain: a Journal of Neurology . 2016;139:1551–1567. doi: 10.1093/brain/aww027. - DOI - PMC - PubMed
    1. Jellinger KA. Recent update on the heterogeneity of the Alzheimer’s disease spectrum. Journal of Neural Transmission (Vienna, Austria: 1996) . 2022;129:1–24. doi: 10.1007/s00702-021-02449-2. - DOI - PubMed
    1. Jack CR, Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimer’s & Dementia: the Journal of the Alzheimer’s Association . 2018;14:535–562. doi: 10.1016/j.jalz.2018.02.018. - DOI - PMC - PubMed

Publication types