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Article ; Online: Influence of Physiological Variables and Comorbidities on Plasma Aβ40, Aβ42, and p-tau181 Levels in Cognitively Unimpaired Individuals.

Martínez-Dubarbie, Francisco / Guerra-Ruiz, Armando / López-García, Sara / Irure-Ventura, Juan / Lage, Carmen / Fernández-Matarrubia, Marta / Pozueta-Cantudo, Ana / García-Martínez, María / Corrales-Pardo, Andrea / Bravo, María / Martín-Arroyo, Juan / Infante, Jon / López-Hoyos, Marcos / García-Unzueta, María Teresa / Sánchez-Juan, Pascual / Rodríguez-Rodríguez, Eloy

International journal of molecular sciences

2024 Volume 25, Issue 3

Abstract: Plasma biomarkers for Alzheimer's disease (AD) are a promising tool that may help in early diagnosis. However, their levels may be influenced by physiological parameters and comorbidities that should be considered before they can be used at the ... ...

Abstract	Plasma biomarkers for Alzheimer's disease (AD) are a promising tool that may help in early diagnosis. However, their levels may be influenced by physiological parameters and comorbidities that should be considered before they can be used at the population level. For this purpose, we assessed the influences of different comorbidities on AD plasma markers in 208 cognitively unimpaired subjects. We analyzed both plasma and cerebrospinal fluid levels of Aβ40, Aβ42, and p-tau181 using the fully automated Lumipulse platform. The relationships between the different plasma markers and physiological variables were studied using linear regression models. The mean differences in plasma markers according to comorbidity groups were also studied. The glomerular filtration rate showed an influence on plasma Aβ40 and Aβ42 levels but not on the Aβ42/Aβ40 ratio. The amyloid ratio was significantly lower in diabetic and hypertensive subjects, and the mean p-tau181 levels were higher in hypertensive subjects. The glomerular filtration rate may have an inverse relationship on plasma Aβ40 and Aβ42 levels but not on the amyloid ratio, suggesting that the latter is a more stable marker to use in the general population. Cardiovascular risk factors might have a long-term effect on the amyloid ratio and plasma levels of p-tau181.
MeSH term(s)	Humans ; Amyloid beta-Peptides/cerebrospinal fluid ; Alzheimer Disease/diagnosis ; Comorbidity ; Biomarkers ; tau Proteins/cerebrospinal fluid ; Peptide Fragments
Chemical Substances	Amyloid beta-Peptides ; Biomarkers ; tau Proteins ; Peptide Fragments
Language	English
Publishing date	2024-01-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25031481
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Article ; Online: Where Should I Draw the Line: PET-Driven, Data-Driven, or Manufacturer Cut-Off?

Sánchez-Soblechero, Antonio / López-García, Sara / Lage, Carmen / Fernández-Matarrubia, Marta / Irure, Juan / López-Hoyos, Marcos / Jiménez-Bonilla, Julio / Quirce, Remedios / de Arcocha-Torres, María / Cuenca-Vera, Oriana / Martín-Arroyo, Juan / Martínez-Dubarbie, Francisco / Pozueta, Ana / García-Martínez, María / Infante, Jon / Sánchez-Juan, Pascual / Rodríguez-Rodríguez, Eloy

Journal of Alzheimer's disease : JAD

2024 Volume 98, Issue 3, Page(s) 957–967

Abstract: Background: The optimal cut-off for Alzheimer's disease (AD) CSF biomarkers remains controversial.: Objective: To analyze the performance of cut-off points standardized by three methods: one that optimized the agreement between 11C-Pittsburgh ... ...

Abstract	Background: The optimal cut-off for Alzheimer's disease (AD) CSF biomarkers remains controversial. Objective: To analyze the performance of cut-off points standardized by three methods: one that optimized the agreement between 11C-Pittsburgh compound B PET (a-PET) and CSF biomarkers (Aβ1-42, pTau, tTau, and Aβ1-42/Aβ1-40 ratio) in our population, called PET-driven; an unbiased cut-off using data from a healthy research cohort, called data-driven, and that provided by the manufacturer. We also compare changes in ATN classification. Methods: CSF biomarkers measured by the LUMIPULSE G600II platform and qualitative visualization of amyloid positron emission tomography (a-PET) were performed in all the patients. We established a cut-off for each single biomarker and Aβ1-42/Aβ1-40 ratio that optimized their agreement with a-PET using ROC curves. Sensitivity, Specificity, and Overall Percent of Agreement are assessed using a-PET or clinical diagnosis as gold standard for every cut-off. Also, we established a data-driven cut-off from our cognitively unimpaired cohort. We then analyzed changes in ATN classification. Results: One hundred and ten patients were recruited. Sixty-six (60%) were a-PET positive. PET-driven cut-offs were: pTau > 57, tTau > 362.62, Aβ1-42/Aβ1-40 < 0.069. For a single biomarker, pTau showed the highest accuracy (AUC 0.926). New PET-driven cut-offs classified patients similarly to manufacturer cut-offs (only two patients changed). However, 20 patients (18%) changed when data-driven cut-offs were used. Conclusions: We established our sample's best CSF biomarkers cut-offs using a-PET as the gold standard. These cut-offs categorize better symptomatic subjects than data-driven in ATN classification, but they are very similar to the manufacturer's.
MeSH term(s)	Humans ; Amyloid beta-Peptides ; tau Proteins ; Alzheimer Disease/diagnostic imaging ; Positron-Emission Tomography ; Biomarkers ; Peptide Fragments
Chemical Substances	Amyloid beta-Peptides ; tau Proteins ; Biomarkers ; Peptide Fragments
Language	English
Publishing date	2024-03-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-230678
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Article ; Online: "This looks like a movie": a case report of post-surgical amnesia.

Pozueta, Ana / García-Martínez, María / Bravo, María / Lage, Carmen / López-García, Sara / Martínez-Dubarbie, Francisco / Corrales-Pardo, Andrea / Sedano-Tous, María José / Sánchez-Juan, Pascual / Rodríguez-Rodríguez, Eloy

Neurocase

2022 Volume 28, Issue 4, Page(s) 410–414

Abstract: A 52-year-old male patient with a background of adaptive personality disorder was admitted for mitral valve repair and cardiac ablation for atrial fibrillation. He suffered intraoperative complications with severe mitral insufficiency that suffered ... ...

Abstract	A 52-year-old male patient with a background of adaptive personality disorder was admitted for mitral valve repair and cardiac ablation for atrial fibrillation. He suffered intraoperative complications with severe mitral insufficiency that suffered ischemia.. Post-operatively, he demonstrated acute loss of retrograde autobiographical memory, prosopagnosia and a loss of public semantic memory. His CT scan was normal and MRI was not possible due to intra-cardiac leads. An initial diagnosis of hypoxic-ischemic encephalopathy was considered. A neuropsychological examination undertaken 20 days after his surgery showed a severe alteration of retrograde autobiographical memory, marked alteration of semantic knowledge and prosopagnosia. He demonstrated an average performance in tasks measuring constructional praxis, visuospatial ability, and executive functions. 34 days after surgery, and after a short nap, the patient "returns" to the day before admission and consequently recovers his memory. Repeat neuropsychological assessment demonstrated performance within the normal range across all previously tested domains. This sudden recovery of memory, together with a normal MRI, led to a rethinking of the diagnosis of dissociative amnesia. This case illustrates the long-standing discussion about the organic or functional origin of some memory disorders, in which, despite advances in neuroimaging techniques, it is still difficult to know their etiology .
MeSH term(s)	Male ; Humans ; Middle Aged ; Motion Pictures ; Prosopagnosia/complications ; Amnesia/etiology ; Memory, Episodic ; Neuropsychological Tests ; Amnesia, Retrograde/diagnosis ; Amnesia, Retrograde/etiology
Language	English
Publishing date	2022-10-19
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	1302651-3
ISSN	1465-3656 ; 1355-4794
ISSN (online)	1465-3656
ISSN	1355-4794
DOI	10.1080/13554794.2022.2136003
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Article ; Online: A rare case of a secondary pituitary abscess arising in a craniopharyngioma with atypical presentation and clinical course.

López Gómez, Patricia / Mato Mañas, David / Bucheli Peñafiel, Carlos / Rodríguez Rodríguez, Eloy Manuel / Pazos Toral, Fernando Antonio / Obeso Aguera, Sergio / Viera Artiles, Jaime / Yange Zambrano, Geanella / Marco de Lucas, Enrique / Martín Láez, Rubén

Neurocirugia (English Edition)

2022 Volume 33, Issue 2, Page(s) 99–104

Abstract: Pituitary abscesses are very uncommon. They are divided into primary, arising within a healthy gland, and secondary, observed with an underlying pre-existing lesion. Here we present the eighth case reported of a secondary abscess within a ... ...

Abstract	Pituitary abscesses are very uncommon. They are divided into primary, arising within a healthy gland, and secondary, observed with an underlying pre-existing lesion. Here we present the eighth case reported of a secondary abscess within a craniopharyngioma. A 59-year-old-woman presented with a 3-week history of headache, and fever. Physical examination was unremarkable. An Magnetic Resonance Imaging (MRI) showed a pituitary lesion suggestive of a chronic inflammatory process. She was diagnosed with lymphocytic meningitis with hypophysitis and she was treated with corticosteroids. Two months later she presented with headache and fever again. Control MRI showed enlargement of the pituitary lesion. Therefore, a transsphenoidal biopsy was performed. During the procedure, purulent material was released. Histological study demonstrated a craniopharyngioma and meningeal inflammation. Empiric antibiotics were started. Three months post-operatively, a follow-up MRI showed a suspect minimal residual mass. Secondary pituitary abscesses are rare. The key to successful management is a high index of suspicion. Transsphenoidal surgical evacuation plus antibiotics is the mainstay of treatment. Although most symptoms resolve, endocrinopathies improve only rarely.
MeSH term(s)	Brain Abscess/diagnostic imaging ; Brain Abscess/etiology ; Craniopharyngioma/complications ; Craniopharyngioma/diagnostic imaging ; Craniopharyngioma/surgery ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Pituitary Diseases/diagnosis ; Pituitary Diseases/pathology ; Pituitary Diseases/surgery ; Pituitary Neoplasms/complications ; Pituitary Neoplasms/diagnostic imaging ; Pituitary Neoplasms/surgery
Language	English
Publishing date	2022-03-04
Publishing country	Spain
Document type	Case Reports
ISSN	2529-8496
ISSN (online)	2529-8496
DOI	10.1016/j.neucie.2020.11.005
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Article ; Online: A rare case of a secondary pituitary abscess arising in a craniopharyngioma with atypical presentation and clinical course.

Neurocirugia (English Edition)

2021

Abstract	Pituitary abscesses are very uncommon. They are divided into primary, arising within a healthy gland, and secondary, observed with an underlying pre-existing lesion. Here we present the eighth case reported of a secondary abscess within a craniopharyngioma. A 59-year-old-woman presented with a 3-week history of headache, and fever. Physical examination was unremarkable. An Magnetic Resonance Imaging (MRI) showed a pituitary lesion suggestive of a chronic inflammatory process. She was diagnosed with lymphocytic meningitis with hypophysitis and she was treated with corticosteroids. Two months later she presented with headache and fever again. Control MRI showed enlargement of the pituitary lesion. Therefore, a transsphenoidal biopsy was performed. During the procedure, purulent material was released. Histological study demonstrated a craniopharyngioma and meningeal inflammation. Empiric antibiotics were started. Three months post-operatively, a follow-up MRI showed a suspect minimal residual mass. Secondary pituitary abscesses are rare. The key to successful management is a high index of suspicion. Transsphenoidal surgical evacuation plus antibiotics is the mainstay of treatment. Although most symptoms resolve, endocrinopathies improve only rarely.
Language	Spanish
Publishing date	2021-02-10
Publishing country	Spain
Document type	Case Reports
ISSN	2529-8496
ISSN (online)	2529-8496
DOI	10.1016/j.neucir.2020.11.008
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Article: Sleep Time Estimated by an Actigraphy Watch Correlates With CSF Tau in Cognitively Unimpaired Elders: The Modulatory Role of APOE.

López-García, Sara / Lage, Carmen / Pozueta, Ana / García-Martínez, María / Kazimierczak, Martha / Fernández-Rodríguez, Andrea / Bravo, María / Reyes-González, Luis / Irure, Juan / López-Hoyos, Marcos / Rodríguez-Rodríguez, Eloy / Sánchez-Juan, Pascual

Frontiers in aging neuroscience

2021 Volume 13, Page(s) 663446

Abstract: There is increasing evidence of the relationship between sleep and neurodegeneration, but this knowledge is not incorporated into clinical practice yet. We aimed to test whether a basic sleep parameter, as total sleep estimated by actigraphy for 1 week, ... ...

Abstract	There is increasing evidence of the relationship between sleep and neurodegeneration, but this knowledge is not incorporated into clinical practice yet. We aimed to test whether a basic sleep parameter, as total sleep estimated by actigraphy for 1 week, was a valid predictor of CSF Alzheimer's Disease core biomarkers (amyloid-β-42 and -40, phosphorylated-tau-181, and total-tau) in elderly individuals, considering possible confounders and effect modifiers, particularly the
Language	English
Publishing date	2021-08-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2558898-9
ISSN	1663-4365
ISSN	1663-4365
DOI	10.3389/fnagi.2021.663446
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Article ; Online: Plasma Phosphorylated Tau 231 Increases at One-Year Intervals in Cognitively Unimpaired Subjects.

Martínez-Dubarbie, Francisco / López-García, Sara / Lage, Carmen / Di Molfetta, Guglielmo / Fernández-Matarrubia, Marta / Pozueta-Cantudo, Ana / García-Martínez, María / Corrales-Pardo, Andrea / Bravo, María / Jiménez-Bonilla, Julio / Quirce, Remedios / Marco de Lucas, Enrique / Drake-Pérez, Marta / Tordesillas, Diana / López-Hoyos, Marcos / Irure-Ventura, Juan / Valeriano-Lorenzo, Elizabeth / Blennow, Kaj / Ashton, Nicholas J /

Zetterberg, Henrik / Rodríguez-Rodríguez, Eloy / Sánchez-Juan, Pascual

Journal of Alzheimer's disease : JAD

2024 Volume 98, Issue 3, Page(s) 1029–1042

Abstract: Background: Plasma biomarkers of Alzheimer's disease (AD) constitute a non-invasive tool for diagnosing and classifying subjects. They change even in preclinical stages, but it is necessary to understand their properties so they can be helpful in a ... ...

Abstract	Background: Plasma biomarkers of Alzheimer's disease (AD) constitute a non-invasive tool for diagnosing and classifying subjects. They change even in preclinical stages, but it is necessary to understand their properties so they can be helpful in a clinical context. Objective: With this work we want to study the evolution of p-tau231 plasma levels in the preclinical stages of AD and its relationship with both cognitive and imaging parameters. Methods: We evaluated plasma phosphorylated (p)-tau231 levels in 146 cognitively unimpaired subjects in sequential visits. We performed a Linear Mixed-effects Model to analyze their rate of change. We also correlated their baseline levels with cognitive tests and structural and functional image values. ATN status was defined based on cerebrospinal fluid biomarkers. Results: Plasma p-tau231 showed a significant rate of change over time. It correlated negatively with memory tests only in amyloid-positive subjects. No significant correlations were found with any imaging measures. Conclusions: Increases in plasma p-tau231 can be detected at one-year intervals in cognitively healthy subjects. It could constitute a sensitive marker for detecting early signs of neuronal network impairment by amyloid.
MeSH term(s)	Humans ; tau Proteins/cerebrospinal fluid ; Alzheimer Disease/diagnostic imaging ; Neuropsychological Tests ; Biomarkers/cerebrospinal fluid ; Amyloid beta-Peptides/cerebrospinal fluid ; Cognitive Dysfunction/psychology
Chemical Substances	tau Proteins ; Biomarkers ; Amyloid beta-Peptides
Language	English
Publishing date	2024-03-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-231479
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Article ; Online: Accuracy of plasma Aβ40, Aβ42, and p-tau181 to detect CSF Alzheimer's pathological changes in cognitively unimpaired subjects using the Lumipulse automated platform.

Martínez-Dubarbie, Francisco / Guerra-Ruiz, Armando / López-García, Sara / Lage, Carmen / Fernández-Matarrubia, Marta / Infante, Jon / Pozueta-Cantudo, Ana / García-Martínez, María / Corrales-Pardo, Andrea / Bravo, María / López-Hoyos, Marcos / Irure-Ventura, Juan / Sánchez-Juan, Pascual / García-Unzueta, María Teresa / Rodríguez-Rodríguez, Eloy

Alzheimer's research & therapy

2023 Volume 15, Issue 1, Page(s) 163

Abstract: Background: The arrival of new disease-modifying treatments for Alzheimer's disease (AD) requires the identification of subjects at risk in a simple, inexpensive, and non-invasive way. With tools allowing an adequate screening, it would be possible to ... ...

Abstract	Background: The arrival of new disease-modifying treatments for Alzheimer's disease (AD) requires the identification of subjects at risk in a simple, inexpensive, and non-invasive way. With tools allowing an adequate screening, it would be possible to optimize the use of these treatments. Plasma markers of AD are very promising, but it is necessary to prove that alterations in their levels are related to alterations in gold standard markers such as cerebrospinal fluid or PET imaging. With this research, we want to evaluate the performance of plasma Aβ40, Aβ42, and p-tau181 to detect the pathological changes in CSF using the automated Lumipulse platform. Methods: Both plasma and CSF Aβ40, Aβ42, and p-tau181 have been evaluated in a group of 208 cognitively unimpaired subjects with a 30.3% of ApoE4 carriers. We have correlated plasma and CSF values of each biomarker. Then, we have also assessed the differences in plasma marker values according to amyloid status (A - / +), AD status (considering AD + subjects to those A + plus Tau +), and ATN group defined by CSF. Finally, ROC curves have been performed, and the area under the curve has been measured using amyloid status and AD status as an outcome and different combinations of plasma markers as predictors. Results: Aβ42, amyloid ratio, p-tau181, and p-tau181/Aβ42 ratio correlated significantly between plasma and CSF. For these markers, the levels were significantly different in the A + / - , AD + / - , and ATN groups. Amyloid ratio predicts amyloid and AD pathology in CSF with an AUC of 0.89. Conclusions: Plasma biomarkers of AD using the automated Lumipulse platform show good diagnostic performance in detecting Alzheimer's pathology in cognitively unimpaired subjects.
MeSH term(s)	Humans ; Alzheimer Disease/diagnostic imaging ; tau Proteins/cerebrospinal fluid ; Amyloid beta-Peptides/cerebrospinal fluid ; Peptide Fragments/cerebrospinal fluid ; Biomarkers/cerebrospinal fluid ; Amyloid
Chemical Substances	amyloid beta-protein (1-42) ; tau Proteins ; Amyloid beta-Peptides ; Peptide Fragments ; Biomarkers ; Amyloid
Language	English
Publishing date	2023-10-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2506521-X
ISSN	1758-9193 ; 1758-9193
ISSN (online)	1758-9193
ISSN	1758-9193
DOI	10.1186/s13195-023-01319-1
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Article ; Online: Age-related hearing loss is not linked to cerebrospinal fluid levels of β-amyloid or p-tau181.

Martínez-Dubarbie, Francisco / Lobo, David / Rollán-Martínez-Herrera, María / López-García, Sara / Lage, Carmen / Fernández-Matarrubia, Marta / Pozueta-Cantudo, Ana / García-Martínez, María / Corrales-Pardo, Andrea / Bravo, María / Cobo, Ramón / Cabieces-Juncal, Daniel / López-Hoyos, Marcos / Irure-Ventura, Juan / Sánchez-Juan, Pascual / Rodríguez-Rodríguez, Eloy

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

2023 Volume 45, Issue 4, Page(s) 1471–1480

Abstract: Introduction: As Hearing loss and dementia affect people with the same profile, several epidemiological studies have evaluated their relationship. However, the link between age-related hearing loss and Alzheimer's disease is still unclear.: Methods: ... ...

Abstract	Introduction: As Hearing loss and dementia affect people with the same profile, several epidemiological studies have evaluated their relationship. However, the link between age-related hearing loss and Alzheimer's disease is still unclear. Methods: We selected subjects with no history of exposure to loud noises, blasts, head trauma with hearing loss, or sudden sensorineural hearing loss from a cohort intended to study preclinical phases of Alzheimer's disease. Participants are volunteers over 55 years without cognitive impairment. We correlated the results of an objective auditory evaluation with brain amyloid and p-tau181 levels and with the outcomes of a comprehensive neuropsychological assessment. Results: Fifty-five subjects at different stages of the Alzheimer's disease continuum were evaluated. There were no statistically significant correlations between amyloid-β and p-tau levels and any of the objective auditory measures. A weak but significant correlation was found between amyloid-β values and the Hearing Handicap Inventory for the Elderly. The neuropsychological domains more correlated to hearing loss were executive function and processing speed. Discussion: Age-related hearing loss is not linked to any pathological markers of Alzheimer's disease nor to neuropsychological domains typically affected in this disease. The Hearing Handicap Inventory for the Elderly has an important component of subjectivity and further studies are needed to explore its relationship with amyloid-β levels.
MeSH term(s)	Humans ; Aged ; Alzheimer Disease/pathology ; tau Proteins/cerebrospinal fluid ; Biomarkers/cerebrospinal fluid ; Amyloid beta-Peptides/cerebrospinal fluid ; Cognitive Dysfunction/cerebrospinal fluid
Chemical Substances	tau Proteins ; Biomarkers ; Amyloid beta-Peptides
Language	English
Publishing date	2023-10-21
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2016546-8
ISSN	1590-3478 ; 1590-1874
ISSN (online)	1590-3478
ISSN	1590-1874
DOI	10.1007/s10072-023-07143-7
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Article ; Online: Correction to: Age‑related hearing loss is not linked to cerebrospinal fluid levels of β‑amyloid or p‑tau181.

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

2023 Volume 45, Issue 4, Page(s) 1811

Language	English
Publishing date	2023-10-31
Publishing country	Italy
Document type	Published Erratum
ZDB-ID	2016546-8
ISSN	1590-3478 ; 1590-1874
ISSN (online)	1590-3478
ISSN	1590-1874
DOI	10.1007/s10072-023-07164-2
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