scholarly journals Sleep Time Estimated by an Actigraphy Watch Correlates With CSF Tau in Cognitively Unimpaired Elders: The Modulatory Role of APOE

2021 ◽  
Vol 13 ◽  
Author(s):  
Sara López-García ◽  
Carmen Lage ◽  
Ana Pozueta ◽  
María García-Martínez ◽  
Martha Kazimierczak ◽  
...  
Keyword(s):  
Brain Aging ◽  
Amyloid Β ◽  
Sleep Time ◽  
Sleep Monitoring ◽  
Valid Predictor ◽  
Early Biomarker ◽  
T Tau ◽  
The Relationship ◽  
Phosphorylated Tau 181

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 APOE ε4 allele. One hundred and twenty-seven cognitively unimpaired volunteers enrolled in the Valdecilla Study for Memory and Brain Aging participated in this study. Seventy percent of the participants were women with a mean age of 65.5 years. After adjustment for covariates, reduced sleep time significantly predicted higher t-tau and p-tau. This association was mainly due to the APOE ε4 carriers. Our findings suggest that total sleep time, estimated by an actigraphy watch, is an early biomarker of tau pathology and that APOE modulates this relationship. The main limitation of this study is the limited validation of the actigraphy technology used. Sleep monitoring with wearables may be a useful and inexpensive screening test to detect early neurodegenerative changes.

scholarly journals The Correlations Between Plasma Fibrinogen With Amyloid-Beta and Tau Levels in Patients With Alzheimer’s Disease

2021 ◽  
Vol 14 ◽  
Author(s):  
Dong-Yu Fan ◽  
Hao-Lun Sun ◽  
Pu-Yang Sun ◽  
Jie-Ming Jian ◽  
Wei-Wei Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Plasma Fibrinogen ◽  
Cognitively Normal ◽  
Amyloid Aβ ◽  
And Gender ◽  
T Tau ◽  
The Relationship ◽  
Phosphorylated Tau 181 ◽  
Normal Controls

Recent studies show that fibrinogen plays a role in the pathogenesis of Alzheimer’s disease (AD), which may be crucial to neurovascular damage and cognitive impairment. However, there are few clinical studies on the relationship between fibrinogen and AD. 59 11C-PiB-PET diagnosed AD patients and 76 age- and gender-matched cognitively normal controls were included to analyze the correlation between plasma β-amyloid (Aβ) and tau levels with fibrinogen levels. 35 AD patients and 76 controls with cerebrospinal fluid (CSF) samples were included to further analyze the correlation between CSF Aβ and tau levels with fibrinogen levels. In AD patients, plasma fibrinogen levels were positively correlated with plasma Aβ40 and Aβ42 levels, and negatively correlated with CSF Aβ42 levels. Besides, fibrinogen levels were positively correlated with CSF total tau (t-tau), and phosphorylated tau-181 (p-tau) levels and positively correlated with the indicators of Aβ deposition in the brain, such as t-tau/Aβ42, p-tau/Aβ42 levels. In normal people, fibrinogen levels lack correlation with Aβ and tau levels in plasma and CSF. This study suggests that plasma fibrinogen levels are positively correlated with Aβ levels in the plasma and brain in AD patients. Fibrinogen may be involved in the pathogenesis of AD.

The relationship between tyramine levels and inflammation in metabolic syndrome

2019 ◽  
Vol 40 (1) ◽  
Author(s):  
Ajay Patel ◽  
Austin Thompson ◽  
Lillian Abdelmalek ◽  
Beverley Adams-Huet ◽  
Ishwarlal Jialal
Keyword(s):  
Metabolic Syndrome ◽  
Early Morning ◽  
National Institutes Of Health ◽  
Atherosclerotic Cardiovascular Disease ◽  
Multiple Biomarkers ◽  
Early Biomarker ◽  
Low Levels ◽  
The Relationship

Abstract Background Metabolic syndrome (MetS) is an important contributor to both type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD). Although MetS affects one third of American adults, its pathogenesis remains to be elucidated. Tyramine, a derivative of tyrosine, has been shown to act as a catecholamine releasing agent in the human body. The aim of this study is to investigate the role of tyramine as an early biomarker for nascent MetS without the confounding of T2DM, ASCVD or smoking. Patients and methods This was an exploratory study of 28 patients with nascent MetS and 20 matched controls carried out in 2018. Metabolites were evaluated from patient’s frozen early morning urine samples and were correlated with biomarkers of inflammation and adipokines. They were assayed by the National Institutes of Health (NIH) Western Metabolomics Center using liquid chromatography/mass spectrometry (LC/MS) and standardized to urinary creatinine. All patients had normal hepatic and renal function. Results Tyramine concentrations were significantly reduced in patients with MetS compared to controls, p = 0.0009. In addition, tyramine was significantly inversely correlated with multiple biomarkers of inflammation and cardiometabolic risk factors such as RBP4, monocyte TLR-4 abundance and P38MAPKinase activity, body mass index (BMI) and blood pressure (BP) (both systolic and diastolic). Conclusion In conclusion, low levels of tyramine could contribute to the proinflammatorty state of MetS.

Diet and Brain Health: Which Role for Polyphenols?

2018 ◽  
Vol 24 (2) ◽  
pp. 227-238 ◽  
Author(s):  
Vanessa Castelli ◽  
Davide Grassi ◽  
Raffaella Bocale ◽  
Michele d'Angelo ◽  
Andrea Antonosante ◽  
...  
Keyword(s):  
Cognitive Performance ◽  
Brain Aging ◽  
Experimental Studies ◽  
Brain Health ◽  
Lifestyle Modifications ◽  
Dietary Polyphenols ◽  
Beneficial Effects ◽  
The Central Nervous System ◽  
The Relationship

Background: The aging of western societies is leading to a dramatic increase in the prevalence of chronic conditions, threatening the health status and then the sustainability of our healthcare systems. In particular, dementia is being increasingly recognized as a public health priority, given its enormous socioeconomic burdens further amplified by the absence of treatments really effective in improving the clinical course of the disease. Methods: The question of whether some degree of cognitive deterioration is an inevitable part of aging or should be considered as a pathological pre-stage of dementia is currently debated. This is a field in need of research because accelerated brain aging as well as further decline in cognition might be preventable in the early stages of cognitive impairment. Herein, we discuss evidence from clinical and experimental studies on the role of polyphenols in preserving cognitive performance across life. Results: In recent years, the possibility of favorably influencing the cognitive trajectory through promotion of lifestyle modifications has been increasingly investigated. In particular, the relationship between nutritional habits and brain health has attracted special attention. Dietary polyphenols exhibit a strong potential to promote brain due to their efficacy in protecting neurons against oxidative stress-induced injury, suppressing neuroinflammation and in ameliorating cardiovascular risk factor control and cardiovascular function thus counteracting neurotoxicity and neurodegeneration. Conclusion: Emerging evidence suggest that dietary polyphenols, in particular flavonoids, may exert beneficial effects on the central nervous system thus representing a potential tool to preserve cognitive performance throught senescence.

scholarly journals The truncated TrkB receptor influences mammalian sleep

2015 ◽  
Vol 308 (3) ◽  
pp. R199-R207 ◽  
Author(s):  
Adam J. Watson ◽  
Kyle Henson ◽  
Susan G. Dorsey ◽  
Marcos G. Frank
Keyword(s):  
Rem Sleep ◽  
Knockout Mice ◽  
Psychiatric Illness ◽  
Sleep Latency ◽  
Sleep Time ◽  
Sleep Regulation ◽  
Trkb Receptor ◽  
Adult Mice ◽  
The Relationship

Brain-derived neurotrophic factor (BDNF) is a neurotrophin hypothesized to play an important role in mammalian sleep expression and regulation. In order to investigate the role of the truncated receptor for BDNF, TrkB.T1, in mammalian sleep, we examined sleep architecture and sleep regulation in adult mice constitutively lacking this receptor. We find that TrkB.T1 knockout mice have increased REM sleep time, reduced REM sleep latency, and reduced sleep continuity. These results demonstrate a novel role for the TrkB.T1 receptor in sleep expression and provide new insights into the relationship between BDNF, psychiatric illness, and sleep.

scholarly journals Dynamic changes of CSF sPDGFRβ during ageing and AD progression and associations with CSF ATN biomarkers

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Jun Wang ◽  
Dong-Yu Fan ◽  
Hui-Yun Li ◽  
Chen-Yang He ◽  
Ying-Ying Shen ◽  
...  
Keyword(s):  
Early Stage ◽  
Growth Factor Receptor ◽  
Early Event ◽  
Dynamic Changes ◽  
Brain Capillary ◽  
Normal Ageing ◽  
T Tau ◽  
Phosphorylated Tau 181 ◽  
Normal Status

Abstract Background Loss of brain capillary pericyte is involved in the pathologies and cognitive deficits in Alzheimer’s disease (AD). The role of pericyte in early stage of AD pathogenesis remains unclear. Methods We investigated the dynamic changes of soluble platelet-derived growth factor receptor β (sPDGFRβ) in cerebrospinal fluid (CSF), a marker of brain pericyte injury, in transition from normal ageing to early AD in a cognitively unimpaired population aged 20 to 90 years. Association between sPDGFRβ and ATN biomarkers were analyzed. Results In lifetime, CSF sPDGFRβ continually increased since age of 20 years, followed by the increases of phosphorylated tau-181 (P-tau181) and total tau (T-tau) at the age of 22.2 years and 31.7 years, respectively; CSF Aβ42 began to decline since the age of 39.6 years, indicating Aβ deposition. The natural trajectories of biomarkers suggest that pericyte injury is an early event during transition from normal status to AD, even earlier than Aβ deposition. In AD spectrum, CSF sPDGFRβ was elevated in preclinical stage 2 and participants with suspected non-AD pathophysiologies. Additionally, CSF sPDGFRβ was positively associated with P-tau181 and T-tau independently of Aβ42, and significantly strengthened the effects of Aβ42 on P-tau181, suggesting that pericyte injury accelerates Aβ-mediated tau hyperphosphorylation. Conclusions Our results suggest that pericyte injury contributes to AD progression in the early stage in an Aβ-independent pathway. Recovery of pericyte function would be a target for prevention and early intervention of AD.

BACE1 and Other Alzheimer’s-Related Biomarkers in Cerebrospinal Fluid and Plasma Distinguish Alzheimer’s Disease Patients from Cognitively-Impaired Neurosyphilis Patients

2020 ◽  
Vol 77 (1) ◽  
pp. 313-322 ◽  
Author(s):  
Min Zhang ◽  
Xiaomei Zhong ◽  
Haishan Shi ◽  
Eugeen Vanmechelen ◽  
Ann De Vos ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Function ◽  
Amyloid Β ◽  
Cognitively Impaired ◽  
Protein Levels ◽  
Scale Scores ◽  
Early Biomarker ◽  
The Relationship

Background: Patients with spirochetal infection, which causes neurosyphilis (NS) and at a later stage general paresis of the insane (GPI), present with brain pathology features of Alzheimer’s disease (AD). However, the relationships among these illnesses regarding biomarker levels are still unclear. Objective: To explore biomarker levels in NS and GPI compared with those in AD and the relationship between biomarker levels and cognitive function in NS and GPI. Methods: Levels of neurogranin (NGRN) and β-amyloid precursor protein cleaving enzyme (BACE1) in cerebrospinal fluid (CSF)/plasma, together with amyloid-β 1–40 (Aβ40), Aβ42, and total tau in the CSF of 23 AD patients, 55 GPI patients, and 13 NS patients were measured. Patients were classified into none-to-mild, moderate, and severe stages of cognitive impairment. Results: Levels of CSF NGRN, BACE1, and tau as well as plasma BACE1 levels were significantly different among groups. In the none-to-mild stage, plasma BACE1 levels correlated with the protein levels in CSF and were significantly increased in AD patients versus GPI patients. The CSF tau levels in AD patients were significantly increased versus GPI patients in the moderate and severe stages. Pooling data from GPI and NS patients, both CSF tau and plasma NGRN levels correlated with cognitive scale scores. Conclusion: GPI and NS patients might have different biomarker level patterns compared to AD patients. While plasma BACE1 could be a promising early biomarker for distinguishing AD from GPI, CSF tau and plasma NGRN levels might be valuable in indications of cognitive function in pooled NS populations.

scholarly journals Neurogranin, a synaptic protein, is associated with memory independent of Alzheimer biomarkers

Neurology ◽  
2017 ◽  
Vol 89 (17) ◽  
pp. 1782-1788 ◽  
Author(s):  
Kaitlin B. Casaletto ◽  
Fanny M. Elahi ◽  
Brianne M. Bettcher ◽  
John Neuhaus ◽  
Barbara B. Bendlin ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Aging ◽  
Brain Aging ◽  
Memory Performance ◽  
Verbal Learning ◽  
Delayed Recall ◽  
Age Related ◽  
T Tau ◽  
The Relationship ◽  
With Memory

Objective:To determine the association between synaptic functioning as measured via neurogranin in CSF and cognition relative to established Alzheimer disease (AD) biomarkers in neurologically healthy older adults.Methods:We analyzed CSF concentrations of neurogranin, β-amyloid (Aβ42), phosphorylated tau (p-tau), and total tau (t-tau) among 132 neurologically normal older adults (mean 64.5, range 55–85), along with bilateral hippocampal volumes and a measure of episodic memory (Auditory Verbal Learning Test, delayed recall). Univariable analyses examined the relationship between neurogranin and the other AD-related biomarkers. Multivariable regression models examined the relationship between neurogranin and delayed recall, adjusting for age and sex, and interaction terms (neurogranin × AD biomarkers).Results:Higher neurogranin concentrations were associated with older age (ρ = 0.20, p = 0.02), lower levels of p-tau and t-tau, and smaller hippocampal volumes (p < 0.03), but not with CSF Aβ42 (p = 0.18). In addition, CSF neurogranin demonstrated a significant relationship with memory performance independent of the AD-related biomarkers; individuals with the lowest CSF neurogranin concentrations performed better on delayed recall than those with medium or high CSF neurogranin concentrations (p < 0.01). Notably, CSF p-tau, t-tau, and Aβ42 and hippocampal volumes were not significantly associated with delayed recall scores (p > 0.40), and did not interact with neurogranin to predict memory (p > 0.10).Conclusions:Synaptic dysfunction (assessed via neurogranin) may be an early pathologic process in age-related neurodegeneration, and a sensitive marker of age-related cognitive abilities, potentially preceding or even acting independently from AD pathogenesis. Synaptic functioning may be a useful early marker of cognitive aging and possibly a target for future brain aging interventions.

Baseline Neurodegeneration Influences the Longitudinal Effects of Tau on Cognition

2021 ◽  
pp. 1-9
Author(s):  
Kok Pin Ng ◽  
Grand H.-L. Cheng ◽  
Chathuri Yatawara ◽  
Pedro Rosa-Neto ◽  
Serge Gauthier ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Impairment ◽  
Amyloid Β ◽  
Cognitive Outcomes ◽  
Longitudinal Effects ◽  
Neuropsychological Assessments ◽  
T Tau

Background: Cerebrospinal fluid t-tau (CSF t-tau) is a measure of neurodegeneration in Alzheimer’s disease (AD) and has been increasingly demonstrated to be a non-specific biomarker within the AD continuum. Objective: We sought to test whether t-tau influences the longitudinal effects of amyloid-β (Aβ) and phospho-tau (p-tau) on memory and executive function (EF) in mild cognitive impairment (MCI). Methods: 319 MCI individuals from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) with baseline and 2-year CSF Aβ, p-tau, t-tau, and neuropsychological assessments were studied. Mediation and moderation analyses evaluated the role of t-tau in the effects of Aβ and p-tau on memory and EF over 2 years. Results: We found that high baseline p-tau but not Aβ was associated with higher t-tau and lower memory scores at 2 years follow-up. The association between p-tau and memory impairment was partially mediated by t-tau, whereby higher p-tau was indirectly associated with lower memory via higher t-tau. t-tau also moderated the association between p-tau and memory. When t-tau level was relatively lower, higher p-tau was associated with lower memory scores at 2 years. When t-tau level was higher, the memory scores were low regardless of the p-tau level. Conclusion: Tau-induced neurodegeneration is one key pathway by which AD pathology (p-tau) affects memory impairment. Furthermore, in individuals with lower levels of tau-induced neurodegeneration, higher levels of p-tau were required for memory impairment. Our findings suggest that t-tau plays a significant role in how early AD pathology affects cognitive outcomes.

scholarly journals Effects of traumatic brain injury on sleep and enlarged perivascular spaces

2018 ◽  
Vol 39 (11) ◽  
pp. 2258-2267 ◽  
Author(s):  
Ryan A Opel ◽  
Alison Christy ◽  
Erin L Boespflug ◽  
Kristianna B Weymann ◽  
Brendan Case ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Total Sleep Time ◽  
Brain Mri ◽  
Sleep Time ◽  
Perivascular Spaces ◽  
History Of ◽  
The Relationship ◽  
The Brain

Clearance of perivascular wastes in the brain may be critical to the pathogenesis of amyloidopathies. Enlarged perivascular spaces (ePVS) on MRI have also been associated with amyloidopathies, suggesting that there may be a mechanistic link between ePVS and impaired clearance. Sleep and traumatic brain injury (TBI) both modulate clearance of amyloid-beta through glymphatic function. Therefore, we sought to evaluate the relationship between sleep, TBI, and ePVS on brain MRI. A retrospective study was performed in individuals with overnight polysomnography and 3T brain MRI consented from a single site ( n = 38). Thirteen of these individuals had a medically confirmed history of TBI. ePVS were visually assessed by blinded experimenters and analyzed in conjunction with sleep metrics and TBI status. Overall, individuals with shorter total sleep time had significantly higher ePVS burden. Furthermore, individuals with TBI showed a stronger relationship between sleep and ePVS compared to the non-TBI group. These results support the hypothesis that ePVS may be modulated by sleep and TBI, and may have implications for the role of the glymphatic system in ePVS.

scholarly journals Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer’s disease

2014 ◽  
Vol 211 (13) ◽  
pp. 2487-2496 ◽  
Author(s):  
Jee Hoon Roh ◽  
Hong Jiang ◽  
Mary Beth Finn ◽  
Floy R. Stewart ◽  
Thomas E. Mahan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Sleep Time ◽  
Poor Sleep ◽  
Age Related ◽  
Aβ Aggregation ◽  
The Brain

Age-related aggregation of amyloid-β (Aβ) is an upstream pathological event in Alzheimer’s disease (AD) pathogenesis, and it disrupts the sleep–wake cycle. The amount of sleep declines with aging and to a greater extent in AD. Poor sleep quality and insufficient amounts of sleep have been noted in humans with preclinical evidence of AD. However, how the amount and quality of sleep affects Aβ aggregation is not yet well understood. Orexins (hypocretins) initiate and maintain wakefulness, and loss of orexin-producing neurons causes narcolepsy. We tried to determine whether orexin release or secondary changes in sleep via orexin modulation affect Aβ pathology. Amyloid precursor protein (APP)/Presenilin 1 (PS1) transgenic mice, in which the orexin gene is knocked out, showed a marked decrease in the amount of Aβ pathology in the brain with an increase in sleep time. Focal overexpression of orexin in the hippocampus in APP/PS1 mice did not alter the total amount of sleep/wakefulness and the amount of Aβ pathology. In contrast, sleep deprivation or increasing wakefulness by rescue of orexinergic neurons in APP/PS1 mice lacking orexin increased the amount of Aβ pathology in the brain. Collectively, modulation of orexin and its effects on sleep appear to modulate Aβ pathology in the brain.

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