P2-115: CEREBROSPINAL FLUID PRESENILIN-1 COMPLEXES: A POTENTIAL BIOMARKER FOR ALZHEIMER'S DISEASE

Background: Synaptic degeneration has been suggested as an early pathological event that strongly correlates with severity of dementia in Alzheimer’s disease (AD). However, changes in longitudinal cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) as a synaptic biomarker in the AD continuum remain unclear. Objective: To assess the trajectory of CSF GAP-43 with AD progression and its association with other AD hallmarks. Methods: CSF GAP-43 was analyzed in 788 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), including 246 cognitively normal (CN) individuals, 415 individuals with mild cognitive impairment (MCI), and 127 with AD dementia based on cognitive assessments. The associations between a multimodal classification scheme with amyloid-β (Aβ), tau, and neurodegeneration, and changes in CSF GAP-43 over time were also analyzed. Results: CSF GAP-43 levels were increased at baseline in MCI and dementia patients, and increased significantly over time in the preclinical (Aβ-positive CN), prodromal (Aβ-positive MCI), and dementia (Aβ-positive dementia) stages of AD. Higher levels of CSF GAP-43 were also associated with higher CSF phosphorylated tau (p-tau) and total tau (t-tau), cerebral amyloid deposition and hypometabolism on positron emission tomography, the hippocampus and middle temporal atrophy, and cognitive performance deterioration at baseline and follow-up. Furthermore, CSF GAP-43 may assist in effectively predicting the probability of dementia onset at 2- or 4-year follow-up. Conclusion: CSF GAP-43 can be used as a potential biomarker associated with synaptic degeneration in subjects with AD; it may also be useful for tracking the disease progression and for monitoring the effects of clinical trials.

Download Full-text

Cerebrospinal Fluid α-Synuclein Predicts Neurodegeneration and Clinical Progression in Prodromal Alzheimer's Disease

10.21203/rs.3.rs-31269/v1 ◽

2020 ◽

Author(s):

Jie-Qiong Li ◽

Yan-Lin Bi ◽

Xue-Ning Shen ◽

Hui-Fu Wang ◽

Wei Xu ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Characteristic Curve ◽

Longitudinal Change ◽

Clinical Progression ◽

Chinese Han ◽

Predictive Values ◽

Potential Biomarker ◽

Prodromal Ad

Abstract BackgroundAccumulating reports suggest that α-synuclein is involved in Alzheimer disease (AD) pathogenesis. Cerebrospinal fluid (CSF) α-synuclein could be a potential biomarker of AD. We sought to test whether CSF α-synuclein is associated with other AD biomarkers and could predict neurodegeneration and clinical progression in prodromal AD. MethodsAssociations were investigated between CSF α-synuclein and other AD biomarkers at baseline in prodromal AD stage Chinese elders. The predictive values of CSF α-synuclein in longitudinal change in clinical outcomes and conversion risk of prodromal AD stage subjects were assessed using linear mixed effects models and multivariate Cox proportional hazard models, respectively, in Alzheimer's disease Neuroimaging Initiative (ADNI) database.ResultsAmong individuals in prodromal AD stage, we detected that CSF α-synuclein levels correlated with AD-specific biomarkers CSF total tau and phosphorylated tau levels in 651 Chinese Han participants (training set). These positive correlations were replicated in ADNI database (validation set). Using a longitudinal cohort from ADNI, CSF α-synuclein concentrations increased with disease severity. CSF α-synuclein had high diagnostic accuracy for AD based on the “ATN” system (A+T+) vs controls (A-T-) (area under the receiver operating characteristic curve, 0.84). Moreover, CSF α-synuclein predicted longitudinal hippocampus atrophy and conversion from MCI to AD dementia.ConclusionsCSF α-synuclein is associated with CSF tau levels and could predict neurodegeneration and clinical progression in prodromal AD. This finding indicates CSF α-synuclein is a potentially useful, early biomarker for AD.

Download Full-text

Extreme cerebrospinal fluid amyloid β levels identify family with late-onset Alzheimer's disease presenilin 1 mutation

Annals of Neurology ◽

10.1002/ana.21099 ◽

2007 ◽

Vol 61 (5) ◽

pp. 446-453 ◽

Cited By ~ 53

Author(s):

John S. K. Kauwe ◽

Sarah Jacquart ◽

Sumi Chakraverty ◽

Jun Wang ◽

Kevin Mayo ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Late Onset ◽

Amyloid Β ◽

Presenilin 1 ◽

Presenilin 1 Mutation

Download Full-text

Cerebrospinal fluid α-synuclein predicts neurodegeneration and clinical progression in non-demented elders

10.21203/rs.3.rs-31269/v5 ◽

2020 ◽

Author(s):

Jie-Qiong Li ◽

Yan-Lin Bi ◽

Xue-Ning Shen ◽

Hui-Fu Wang ◽

Wei Xu ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Characteristic Curve ◽

Control Area ◽

Clinical Progression ◽

Chinese Han ◽

Predictive Values ◽

Potential Biomarker ◽

Validation Set

Abstract Background Accumulating reports have suggested that α-synuclein is involved in the pathogenesis of Alzheimer’s disease (AD). As the cerebrospinal fluid (CSF) α-synuclein has been suggested as a potential biomarker of AD, this study was set out to test whether CSF α-synuclein is associated with other AD biomarkers and could predict neurodegeneration and clinical progression in non-demented elders. Methods The associations between CSF α-synuclein and other AD biomarkers were investigated at baseline in non-demented Chinese elders. The predictive values of CSF α-synuclein for longitudinal neuroimaging change and the conversion risk of non-demented elders were assessed using linear mixed effects models and multivariate Cox proportional hazard models, respectively, in the Alzheimer's disease Neuroimaging Initiative (ADNI) database.Results The CSF α-synuclein levels correlated with AD-specific biomarkers, CSF total tau and phosphorylated tau levels, in 651 Chinese Han participants (training set). These positive correlations were replicated in the ADNI database (validation set). Using a longitudinal cohort from ADNI, the CSF α-synuclein concentrations were found to increase with disease severity. The CSF α-synuclein had high diagnostic accuracy for AD based on the “ATN” (amyloid, tau, neurodegeneration) system (A+T+ versus A−T−control) (area under the receiver operating characteristic curve, 0.84). Moreover, CSF α-synuclein predicted longitudinal hippocampus atrophy and conversion from MCI to AD dementia.Conclusions CSF α-synuclein is associated with CSF tau levels and could predict neurodegeneration and clinical progression in non-demented elders. This finding indicates that CSF α-synuclein is a potentially useful early biomarker for AD.

Download Full-text

Cerebrospinal fluid α-synuclein predicts neurodegeneration and clinical progression in non-demented elders

Translational Neurodegeneration ◽

10.1186/s40035-020-00222-1 ◽

2020 ◽

Vol 9 (1) ◽

Author(s):

Jie-Qiong Li ◽

◽

Yan-Lin Bi ◽

Xue-Ning Shen ◽

Hui-Fu Wang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Characteristic Curve ◽

Control Area ◽

Clinical Progression ◽

Chinese Han ◽

Predictive Values ◽

Potential Biomarker ◽

Validation Set

Abstract Background Accumulating reports have suggested that α-synuclein is involved in the pathogenesis of Alzheimer’s disease (AD). As the cerebrospinal fluid (CSF) α-synuclein has been suggested as a potential biomarker of AD, this study was set out to test whether CSF α-synuclein is associated with other AD biomarkers and could predict neurodegeneration and clinical progression in non-demented elders. Methods The associations between CSF α-synuclein and other AD biomarkers were investigated at baseline in non-demented Chinese elders. The predictive values of CSF α-synuclein for longitudinal neuroimaging change and the conversion risk of non-demented elders were assessed using linear mixed effects models and multivariate Cox proportional hazard models, respectively, in the Alzheimer’s disease Neuroimaging Initiative (ADNI) database. Results The CSF α-synuclein levels correlated with AD-specific biomarkers, CSF total tau and phosphorylated tau levels, in 651 Chinese Han participants (training set). These positive correlations were replicated in the ADNI database (validation set). Using a longitudinal cohort from ADNI, the CSF α-synuclein concentrations were found to increase with disease severity. The CSF α-synuclein had high diagnostic accuracy for AD based on the “ATN” (amyloid, tau, neurodegeneration) system (A + T+ versus A − T − control) (area under the receiver operating characteristic curve, 0.84). Moreover, CSF α-synuclein predicted longitudinal hippocampus atrophy and conversion from MCI to AD dementia. Conclusions CSF α-synuclein is associated with CSF tau levels and could predict neurodegeneration and clinical progression in non-demented elders. This finding indicates that CSF α-synuclein is a potentially useful early biomarker for AD.

Download Full-text

Asymptomatic Carriers of Presenilin-1 E318G Variant Show no Cerebrospinal Fluid Biochemical Signs Suggestive of Alzheimer’s disease in a Family with Late-onset Dementia

Current Alzheimer Research ◽

10.2174/1567205015666181031150345 ◽

2018 ◽

Vol 16 (1) ◽

pp. 1-7

Author(s):

Vladimiro Artuso ◽

Luisa Benussi ◽

Roberta Ghidoni ◽

Soraya Moradi-Bachiller ◽

Federica Fusco ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Late Onset ◽

Presenilin 1 ◽

Amyloid Peptides ◽

Csf Levels ◽

T Tau ◽

Late Onset Dementia

Background: Presenilin-1 (PSEN-1) is a component of the γ-secretase complex involved in β-amyloid Precursor Protein (AβPP) processing. Usually, Alzheimer’s disease (AD)-linked mutations in the PSEN-1 gene lead to the early onset and increase the production of the aggregation-prone peptide Aβ42. However, the PSEN-1 E318G variant has an unclear pathogenic role and is recently reported as a genetic risk factor for AD. In particular, E318G variant presence correlated with increased cerebrospinal fluid (CSF) levels of Total Tau (t-tau) and Phosphorylated Tau (p-tau). Objective: We describe a large Italian family, which we followed from January 2003 to January 2018, with the late-onset AD and the E318G variant, with the aim of assessing E318G-associated CSF or plasma biochemical changes in biomarkers of dementia. Method: CSF Aβ42, t-tau and p-tau, plasma Aβ42 and Aβ40 were assessed by ELISA tests, while CSF amyloid peptides profile was investigated by mass spectrometry. Results: We did not find any changes in CSF biochemical markers (Aβ42, t-tau, p-tau and amyloid peptides) of asymptomatic E318G carriers in 2010 and 2012, but plasma Aβ40 was increased at the same times. From 2003 to 2018, no asymptomatic E318G carrier developed AD. Conclusion: Our follow-up of this family may help elucidate E318G’s role in AD and globally points to a null effect of this variant.

Download Full-text