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Article ; Online: Human in vivo evidence of associations between herpes simplex virus and cerebral amyloid-beta load in normal aging.

Cantero, Jose L / Atienza, Mercedes / Sastre, Isabel / Bullido, María Jesús

2024 Volume 16, Issue 1, Page(s) 68

Abstract: Background: Mounting data suggests that herpes simplex virus type 1 (HSV-1) is involved in the pathogenesis of AD, possibly instigating amyloid-beta (Aβ) accumulation decades before the onset of clinical symptoms. However, human in vivo evidence linking ...

Abstract	Background: Mounting data suggests that herpes simplex virus type 1 (HSV-1) is involved in the pathogenesis of AD, possibly instigating amyloid-beta (Aβ) accumulation decades before the onset of clinical symptoms. However, human in vivo evidence linking HSV-1 infection to AD pathology is lacking in normal aging, which may contribute to the elucidation of the role of HSV-1 infection as a potential AD risk factor. Methods: To shed light into this question, serum anti-HSV IgG levels were correlated with Results: We showed that increased anti-HSV IgG levels are associated with higher Aβ load in fronto-temporal regions of cognitively normal older adults. Remarkably, these cortical regions exhibited abnormal patterns of resting state-functional connectivity (rs-FC) only in those individuals showing the highest levels of anti-HSV IgG. We further found that positive relationships between anti-HSV IgG levels and Aβ load, particularly in the anterior cingulate cortex, are moderated by the APOE4 genotype, the strongest genetic risk factor for AD. Importantly, anti-HSV IgG levels were unrelated to either subclinical cognitive deficits or to blood markers of neurodegeneration. Conclusions: All together, these results suggest that HSV infection is selectively related to cortical Aβ deposition in normal aging, supporting the inclusion of cognitively normal older adults in prospective trials of antimicrobial therapy aimed at decreasing the AD risk in the aging population.
MeSH term(s)	Humans ; Aged ; Apolipoprotein E4 ; Prospective Studies ; Amyloid beta-Peptides/metabolism ; Herpesvirus 1, Human/metabolism ; Herpes Simplex/diagnostic imaging ; Herpes Simplex/metabolism ; Aging/metabolism ; Immunoglobulin G ; Alzheimer Disease/diagnosis
Chemical Substances	Apolipoprotein E4 ; Amyloid beta-Peptides ; Immunoglobulin G
Language	English
Publishing date	2024-04-03
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/s13195-024-01437-4
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Article ; Online: Cortical amyloid-beta burden is associated with changes in intracortical myelin in cognitively normal older adults.

Fernandez-Alvarez, Marina / Atienza, Mercedes / Cantero, Jose L

Translational psychiatry

2023 Volume 13, Issue 1, Page(s) 115

Abstract: Amyloid-beta (Aβ) aggregates and myelin breakdown are among the earliest detrimental effects of Alzheimer's disease (AD), likely inducing abnormal patterns of neuronal communication within cortical networks. However, human in vivo evidence linking Aβ ... ...

Abstract	Amyloid-beta (Aβ) aggregates and myelin breakdown are among the earliest detrimental effects of Alzheimer's disease (AD), likely inducing abnormal patterns of neuronal communication within cortical networks. However, human in vivo evidence linking Aβ burden, intracortical myelin, and cortical synchronization is lacking in cognitively normal older individuals. Here, we addressed this question combining
MeSH term(s)	Humans ; Aged ; Myelin Sheath/metabolism ; Magnetic Resonance Imaging/methods ; Amyloid beta-Peptides/metabolism ; Alzheimer Disease/metabolism ; Cognitive Dysfunction/diagnostic imaging ; Cognitive Dysfunction/metabolism ; Positron-Emission Tomography
Chemical Substances	Amyloid beta-Peptides
Language	English
Publishing date	2023-04-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2609311-X
ISSN	2158-3188 ; 2158-3188
ISSN (online)	2158-3188
ISSN	2158-3188
DOI	10.1038/s41398-023-02420-7
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Article ; Online: Effects of non-modifiable risk factors of Alzheimer's disease on intracortical myelin content.

Fernandez-Alvarez, Marina / Atienza, Mercedes / Cantero, Jose L

Alzheimer's research & therapy

2022 Volume 14, Issue 1, Page(s) 202

Abstract: Background: Non-modifiable risk factors of Alzheimer's disease (AD) have lifelong effects on cortical integrity that could be mitigated if identified at early stages. However, it remains unknown whether cortical microstructure is affected in older ... ...

Abstract	Background: Non-modifiable risk factors of Alzheimer's disease (AD) have lifelong effects on cortical integrity that could be mitigated if identified at early stages. However, it remains unknown whether cortical microstructure is affected in older individuals with non-modifiable AD risk factors and whether altered cortical tissue integrity produces abnormalities in brain functional networks in this AD-risk population. Methods: Using relative T1w/T2w (rT1w/T2w) ratio maps, we have compared tissue integrity of normal-appearing cortical GM between controls and cognitively normal older adults with either APOE4 (N = 50), with a first-degree family history (FH) of AD (N = 52), or with the co-occurrence of both AD risk factors (APOE4+FH) (N = 35). Additionally, individuals with only one risk factor (APOE4 or FH) were combined into one group (N = 102) and compared with controls. The same number of controls matched in age, sex, and years of education was employed for each of these comparisons. Group differences in resting state functional connectivity (rs-FC) patterns were also investigated, using as FC seeds those cortical regions showing significant changes in rT1w/T2w ratios. Results: Overall, individuals with non-modifiable AD risk factors exhibited significant variations in rT1w/T2w ratios compared to controls, being APOE4 and APOE4+FH at opposite ends of a continuum. The co-occurrence of APOE4 and FH was further accompanied by altered patterns of rs-FC. Conclusions: These findings may have practical implications for early detection of cortical abnormalities in older populations with APOE4 and/or FH of AD and open new avenues to monitor changes in cortical tissue integrity associated with non-modifiable AD risk factors.
MeSH term(s)	Humans ; Aged ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/genetics ; Apolipoprotein E4/genetics ; Myelin Sheath ; Magnetic Resonance Imaging ; Brain ; Risk Factors
Chemical Substances	Apolipoprotein E4
Language	English
Publishing date	2022-12-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2506521-X
ISSN	1758-9193 ; 1758-9193
ISSN (online)	1758-9193
ISSN	1758-9193
DOI	10.1186/s13195-022-01152-y
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Article ; Online: Characterization of Extracellular Vesicles from Human Saliva: Effects of Age and Isolation Techniques.

Reseco, Lucia / Molina-Crespo, Angela / Atienza, Mercedes / Gonzalez, Esperanza / Falcon-Perez, Juan Manuel / Cantero, Jose L

Cells

2024 Volume 13, Issue 1

Abstract: Salivary extracellular vesicles (EVs) represent an attractive source of biomarkers due to the accessibility of saliva and its non-invasive sampling methods. However, the lack of comparative studies assessing the efficacy of different EV isolation ... ...

Abstract	Salivary extracellular vesicles (EVs) represent an attractive source of biomarkers due to the accessibility of saliva and its non-invasive sampling methods. However, the lack of comparative studies assessing the efficacy of different EV isolation techniques hampers the use of salivary EVs in clinical settings. Moreover, the effects of age on salivary EVs are largely unknown, hindering the identification of salivary EV-associated biomarkers across the lifespan. To address these questions, we compared salivary EV concentration, size mode, protein concentration, and purity using eight EV isolation techniques before and after magnetic bead immunocapture with antibodies against CD9, CD63, and CD81. The effects of age on salivary EVs obtained with each isolation technique were further investigated. Results showed higher expression of CD63 on isolated salivary EVs compared to the expression of CD81 and flotillin-1. Overall, magnetic bead immunocapture was more efficient in recovering salivary EVs with Norgen's Saliva Exosome Purification Kit and ExoQuick-TC ULTRA at the cost of EV yield. Regardless of age, Invitrogen Total Exosome Isolation Solution showed the highest level of protein concentration, whereas Izon qEVOriginal-70nm columns revealed the highest purity. This study provides the first comprehensive comparison of salivary EVs in younger and older adults using different EV isolation techniques, which represents a step forward for assessing salivary EVs as a source of potential biomarkers of tissue-specific diseases throughout the life cycle.
MeSH term(s)	Humans ; Aged ; Saliva ; Extracellular Vesicles ; Exosomes ; Antibodies ; Biomarkers
Chemical Substances	Antibodies ; Biomarkers
Language	English
Publishing date	2024-01-02
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells13010095
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Article ; Online: Stability of neural encoding moderates the contribution of sleep and repeated testing to memory consolidation.

Baena, Daniel / Cantero, Jose L / Atienza, Mercedes

Neurobiology of learning and memory

2021 Volume 185, Page(s) 107529

Abstract: There is evidence suggesting that online consolidation during retrieval-mediated learning interacts with offline consolidation during subsequent sleep to transform memory. Here we investigate whether this interaction persists when retrieval-mediated ... ...

Abstract	There is evidence suggesting that online consolidation during retrieval-mediated learning interacts with offline consolidation during subsequent sleep to transform memory. Here we investigate whether this interaction persists when retrieval-mediated learning follows post-training sleep and whether the direction of this interaction is conditioned by the quality of encoding resulting from manipulation of the amount of sleep on the previous night. The quality of encoding was determined by computing the degree of similarity between EEG-activity patterns across restudy of face pairs in two groups of young participants, one who slept the last 4 h of the pre-training night, and another who slept 8 h. The offline consolidation was assessed by computing the degree of coupling between slow oscillations (SOs) and spindles (SPs) during post-training sleep, while the online consolidation was evaluated by determining the degree of similarity between EEG-activity patterns recorded during the study phase and during repeated recognition of either the same face pair (i.e., specific similarity) or face pairs sharing sex and profession (i.e., categorical similarity) to evaluate differentiation and generalization, respectively. The study and recognition phases were separated by a night of normal sleep duration. Mixed-effects models revealed that the stability of neural encoding moderated the relationship between sleep- and retrieval-mediated consolidation processes over left frontal regions. For memories showing lower encoding stability, the enhanced SO-SP coupling was associated with increased reinstatement of category-specific encoding-related activity at the expense of content-specific activity, whilst the opposite occurred for memories showing greater encoding stability. Overall, these results suggest that offline consolidation during post-training sleep interacts with online consolidation during retrieval the next day to favor the reorganization of memory contents, by increasing specificity of stronger memories and generalization of the weaker ones.
MeSH term(s)	Adolescent ; Adult ; Electroencephalography ; Facial Recognition/physiology ; Female ; Humans ; Male ; Memory/physiology ; Memory Consolidation/physiology ; Sleep/physiology ; Young Adult
Language	English
Publishing date	2021-09-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1223366-3
ISSN	1095-9564 ; 1074-7427
ISSN (online)	1095-9564
ISSN	1074-7427
DOI	10.1016/j.nlm.2021.107529
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Article ; Online: Blood total antioxidant status is associated with cortical glucose uptake and factors related to accelerated aging.

Palomar-Bonet, Miriam / Atienza, Mercedes / Cantero, Jose L

Brain structure & function

2020 Volume 225, Issue 2, Page(s) 841–851

Abstract: Identifying cerebral vulnerability in late life is of paramount importance to prevent pathological trajectories of aging before the onset of symptoms. Considerable evidence suggests that impaired antioxidant mechanisms are a fingerprint of aging-related ... ...

Abstract	Identifying cerebral vulnerability in late life is of paramount importance to prevent pathological trajectories of aging before the onset of symptoms. Considerable evidence suggests that impaired antioxidant mechanisms are a fingerprint of aging-related conditions, but there is a lack of human research linking total antioxidant capacity (TAC) measured in peripheral blood to in vivo brain changes and other factors featuring accelerated aging. To address this issue, we have assessed in cognitively normal elderly subjects (N = 100) correlations between serum TAC, using the oxygen radical absorbance capacity assay, surface-based cortical thickness, surface-based 18F-fluorodeoxyglucose positron emission tomography cortical uptake, and different factors associated with accelerated aging [i.e., serum homocysteine (HCY), self-reported memory problems, and self-reported patterns of physical activity]. While no relationship was observed between serum TAC and variations in cortical thickness, decreased TAC level was significantly associated with lower FDG uptake in temporal lobes bilaterally. Remarkably, decreased TAC level was linked to increased HCY concentrations, more subjective memory complaints, and lower frequency of physical activity. Overall, our results suggest that decreased serum TAC level may be helpful to detect vulnerable trajectories of aging.
MeSH term(s)	Aged ; Aging/blood ; Antioxidants/metabolism ; Brain/metabolism ; Female ; Fluorodeoxyglucose F18 ; Glucose/metabolism ; Homocysteine/blood ; Humans ; Male ; Middle Aged ; Oxygen Radical Absorbance Capacity ; Positron-Emission Tomography
Chemical Substances	Antioxidants ; Homocysteine (0LVT1QZ0BA) ; Fluorodeoxyglucose F18 (0Z5B2CJX4D) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2020-02-11
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2273162-3
ISSN	1863-2661 ; 1863-2653
ISSN (online)	1863-2661
ISSN	1863-2653
DOI	10.1007/s00429-020-02039-0
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Article: Lower serum expression of miR-181c-5p is associated with increased plasma levels of amyloid-beta 1-40 and cerebral vulnerability in normal aging.

Manzano-Crespo, Marta / Atienza, Mercedes / Cantero, Jose L

Translational neurodegeneration

2019 Volume 8, Page(s) 34

Abstract: Background: Previous studies have shown that expression levels of miR-181c are downregulated by amyloid-β (Aβ) deposition and chronic cerebral hypoperfusion, both factors largely associated with the development of AD. Moreover, reduced 2-[18F]fluoro-2- ... ...

Abstract	Background: Previous studies have shown that expression levels of miR-181c are downregulated by amyloid-β (Aβ) deposition and chronic cerebral hypoperfusion, both factors largely associated with the development of AD. Moreover, reduced 2-[18F]fluoro-2-deoxy-D-glucose (FDG)-PET brain metabolism and volume loss of regions of the medial temporal lobe have been generally recognized as hallmarks of AD. Based on this evidence, we have here investigated potential associations between serum levels of miR-181c-5p and these AD signatures in asymptomatic elderly subjects. Methods: Ninety-five normal elderly subjects underwent clinical, cognitive, structural MRI, and FDG-PET explorations. Serum expression levels of miR-181c-5p and plasma Aβ concentrations were further analyzed in this cohort. Regression analyses were performed to assess associations between serum miR-181c-5p levels and cognitive functioning, plasma Aβ, structural and metabolic brain changes. Results: Decreased serum expression of miR-181c-5p was associated with increased plasma levels of Aβ Conclusions: These findings suggest that deregulation of serum miR-181c-5p may indicate cerebral vulnerability in late life.
Language	English
Publishing date	2019-11-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2653701-1
ISSN	2047-9158
ISSN	2047-9158
DOI	10.1186/s40035-019-0174-8
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Article ; Online: Weakly encoded memories due to acute sleep restriction can be rescued after one night of recovery sleep.

Baena, Daniel / Cantero, Jose L / Fuentemilla, Lluís / Atienza, Mercedes

Scientific reports

2020 Volume 10, Issue 1, Page(s) 1449

Abstract: Sleep is thought to play a complementary role in human memory processing: sleep loss impairs the formation of new memories during the following awake period and, conversely, normal sleep promotes the strengthening of the already encoded memories. However, ...

Abstract	Sleep is thought to play a complementary role in human memory processing: sleep loss impairs the formation of new memories during the following awake period and, conversely, normal sleep promotes the strengthening of the already encoded memories. However, whether sleep can strengthen deteriorated memories caused by insufficient sleep remains unknown. Here, we showed that sleep restriction in a group of participants caused a reduction in the stability of EEG activity patterns across multiple encoding of the same event during awake, compared with a group of participants that got a full night's sleep. The decrease of neural stability patterns in the sleep-restricted group was associated with higher slow oscillation-spindle coupling during a subsequent night of normal sleep duration, thereby suggesting the instantiation of restorative neural mechanisms adaptively supporting cognition and memory. Importantly, upon awaking, the two groups of participants showed equivalent retrieval accuracy supported by subtle differences in the reinstatement of encoding-related activity: it was longer lasting in sleep-restricted individuals than in controls. In addition, sustained reinstatement over time was associated with increased coupling between spindles and slow oscillations. Taken together, these results suggest that the strength of prior encoding might be an important moderator of memory consolidation during sleep. Supporting this view, spindles nesting in the slow oscillation increased the probability of correct recognition only for weakly encoded memories. Current results demonstrate the benefit that a full night's sleep can induce to impaired memory traces caused by an inadequate amount of sleep.
MeSH term(s)	Adolescent ; Adult ; Cognition/physiology ; Female ; Humans ; Male ; Memory/physiology ; Memory Consolidation/physiology ; Memory Disorders/therapy ; Physical Therapy Modalities ; Recovery of Function ; Sleep Deprivation/therapy ; Sleep Stages ; Sleep, Slow-Wave ; Young Adult
Language	English
Publishing date	2020-01-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-58496-4
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Article ; Online: Salivary lactoferrin is associated with cortical amyloid-beta load, cortical integrity, and memory in aging.

Reseco, Lucia / Atienza, Mercedes / Fernandez-Alvarez, Marina / Carro, Eva / Cantero, Jose L

Alzheimer's research & therapy

2021 Volume 13, Issue 1, Page(s) 150

Abstract: Background: Aging is associated with declining protective immunity and persistent low-grade inflammatory responses, which significantly contribute to Alzheimer's disease (AD) pathogenesis. Detecting aging-related cerebral vulnerability associated with ... ...

Abstract	Background: Aging is associated with declining protective immunity and persistent low-grade inflammatory responses, which significantly contribute to Alzheimer's disease (AD) pathogenesis. Detecting aging-related cerebral vulnerability associated with deterioration of the immune system requires from non-invasive biomarkers able to detect failures in the brain-immunity connection. Reduced levels of salivary lactoferrin (sLF), an iron-binding protein with immunomodulatory activity, have been related to AD diagnosis. However, it remains unknown whether decreased sLF is associated with increased cortical amyloid-beta (Aβ) load and/or with loss of cortical integrity in normal aging. Methods: Seventy-four cognitively normal older adults (51 females) participated in the study. We applied multiple linear regression analyses to assess (i) whether sLF is associated with cortical Aβ load measured by 18F-Florbetaben (FBB)-positron emission tomography (PET), (ii) whether sLF-related variations in cortical thickness and cortical glucose metabolism depend on global Aβ burden, and (iii) whether such sLF-related cortical abnormalities moderate the relationship between sLF and cognition. Results: sLF was negatively associated with Aβ load in parieto-temporal regions. Moreover, sLF was related to thickening of the middle temporal cortex, increased FDG uptake in the posterior cingulate cortex, and poorer memory. These associations were stronger in individuals showing the highest Aβ burden. Conclusions: sLF levels are sensitive to variations in cortical Aβ load, structural and metabolic cortical abnormalities, and subclinical memory impairment in asymptomatic older adults. These findings provide support for the use of sLF as a non-invasive biomarker of cerebral vulnerability in the general aging population.
MeSH term(s)	Aged ; Aging ; Alzheimer Disease/diagnostic imaging ; Amyloid beta-Peptides/metabolism ; Female ; Humans ; Lactoferrin ; Positron-Emission Tomography
Chemical Substances	Amyloid beta-Peptides ; Lactoferrin (EC 3.4.21.-)
Language	English
Publishing date	2021-09-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2506521-X
ISSN	1758-9193 ; 1758-9193
ISSN (online)	1758-9193
ISSN	1758-9193
DOI	10.1186/s13195-021-00891-8
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Article ; Online: Associations of Salivary Total Antioxidant Capacity With Cortical Amyloid-Beta Burden, Cortical Glucose Uptake, and Cognitive Function in Normal Aging.

Palomar-Bonet, Miriam / Atienza, Mercedes / Hernández-Ledesma, Blanca / Cantero, Jose L

The journals of gerontology. Series A, Biological sciences and medical sciences

2021 Volume 76, Issue 10, Page(s) 1839–1845

Abstract: Background: Determining susceptibility to Alzheimer's disease (AD) in asymptomatic individuals requires from noninvasive, simple, and inexpensive markers that can be easily obtained in primary care settings. While saliva meets all these requirements, ... ...

Abstract	Background: Determining susceptibility to Alzheimer's disease (AD) in asymptomatic individuals requires from noninvasive, simple, and inexpensive markers that can be easily obtained in primary care settings. While saliva meets all these requirements, there is a lack of evidence linking salivary constituents to in vivo AD pathology in aging. Methods: We examined the potential of salivary total antioxidant capacity (TAC) for identifying global cortical amyloid-beta (Aβ) burden, deficits in regional glucose uptake, and poorer cognition in 71 cognitively normal older adults. We further assessed whether salivary TAC-related cognitive performance was associated with higher Aβ load and lower cortical glucose consumption. Results: Linear regression analyses adjusted by age, sex, years of education, and ApoE4 status showed that salivary TAC was associated with slower processing speed and poorer sustained attention, as well as with higher Aβ load and lower glucose metabolism in cortical regions vulnerable to cognitive aging and AD. Results also revealed that lower scores in processing speed and sustained attention were associated with greater Aβ burden and lower regional glucose consumption, respectively. Conclusions: Together, these findings support the use of salivary TAC for preventive screening and detection of cerebral vulnerability to AD. Further research is needed to evaluate the utility of salivary TAC as a clinical marker.
MeSH term(s)	Aged ; Aging ; Alzheimer Disease ; Amyloid beta-Peptides/metabolism ; Antioxidants ; Brain/metabolism ; Cognition ; Cognitive Dysfunction ; Glucose ; Humans ; Positron-Emission Tomography
Chemical Substances	Amyloid beta-Peptides ; Antioxidants ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2021-01-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1223643-3
ISSN	1758-535X ; 1079-5006
ISSN (online)	1758-535X
ISSN	1079-5006
DOI	10.1093/gerona/glab034
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