scholarly journals Association of naturally occurring antibodies to β-amyloid with cognitive decline and cerebral amyloidosis in Alzheimer’s disease

2021 ◽  
Vol 7 (1) ◽  
pp. eabb0457
Author(s):  
Yu-Hui Liu ◽  
Jun Wang ◽  
Qiao-Xin Li ◽  
Christopher J. Fowler ◽  
Fan Zeng ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Plasma Levels ◽  
Imaging Biomarkers ◽  
Amino Terminus ◽  
Cross Sectional ◽  
Naturally Occurring ◽  
Β Amyloid ◽  
Naturally Occurring Antibodies

The pathological relevance of naturally occurring antibodies to β-amyloid (NAbs-Aβ) in Alzheimer’s disease (AD) remains unclear. We aimed to investigate their levels and associations with Aβ burden and cognitive decline in AD in a cross-sectional cohort from China and a longitudinal cohort from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. NAbs-Aβ levels in plasma and cerebrospinal fluid (CSF) were tested according to their epitopes. Levels of NAbs targeting the amino terminus of Aβ increased, and those targeting the mid-domain of Aβ decreased in both CSF and plasma in AD patients. Higher plasma levels of NAbs targeting the amino terminus of Aβ and lower plasma levels of NAbs targeting the mid-domain of Aβ were associated with higher brain amyloidosis at baseline and faster cognitive decline during follow-up. Our findings suggest a dynamic response of the adaptive immune system in the progression of AD and are relevant to current passive immunotherapeutic strategies.

scholarly journals Naturally Occurring Antibodies Against Bim Are Decreased in Alzheimer’s Disease and Attenuate Ad-type Pathologies in a Mouse Model

2021 ◽  
Author(s):  
Jie-Ming Jian ◽  
Dong-Yu Fan ◽  
Ding-Yuan Tian ◽  
Yuan Cheng ◽  
Pu-Yang Sun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Cognitive Functions ◽  
Plasma Levels ◽  
Neuronal Apoptosis ◽  
Precursor Protein ◽  
Cognitively Normal ◽  
Naturally Occurring ◽  
Naturally Occurring Antibodies

Abstract Background Alzheimer’s disease (AD) is the most popular neurodegenerative disease affecting cognitive functions of the elderly population. Neuronal apoptosis is an important pathological process during the development of AD. The Bcl-2-interacting mediator of cell death (Bim) mediates Amyloid-beta (Aβ)-induced neuronal apoptosis. Naturally occurring antibodies against Bim (NAbs-Bim) exist in human blood, with their levels and functions unknown in AD. Methods This study investigated the clinical relevance of plasma NAbs-Bim to AD in 55 AD patients, 28 patients with non-AD dementia, and 70 cognitively normal subjects. Furthermore, the pathophysiological functions of NAbs-Bim were explored in APP/PS1 mice and SY5Y cell lines overexpressing human amyloid precursor protein (APP). Results We found that plasma levels of NAbs-Bim were lower in AD patients in comparison with patients with non-AD dementia and cognitively normal controls. Plasma levels of NAbs-Bim were negatively associated with brain amyloid burdens and positively associated with cognitive functions. NAbs-Bim purified from intravenous immunoglobulin rescued behavioral deficits of APP/PS1 mice. NAbs-Bim ameliorated Aβ deposition, Tau hyperphosphorylation, microgliosis and neuronal apoptosis in APP/PS1 mice. In vitro investigations demonstrated that NAbs-Bim exerted neuroprotective effects against AD through neutralizing Bim-directed neuronal apoptosis and amyloidogenic processing of amyloid precursor protein. Conclusions The decrease of NAbs-Bim might contribute to the pathogenesis of AD and immunotherapies targeting Bim may hold promise for the treatment of AD.

SUBJECTIVE COGNITIVE DECLINE, LONGITUDINAL COGNITIVE PERFORMANCE, AND IMAGING BIOMARKERS IN PRECLINICAL ALZHEIMER’S DISEASE

2017 ◽  
Vol 13 (7) ◽  
pp. P176
Author(s):  
Rebecca Amariglio ◽  
Rachel F. Buckley ◽  
Beth C. Mormino ◽  
Cathy Wang ◽  
Sarah L. Aghjayan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Cognitive Performance ◽  
Imaging Biomarkers ◽  
Subjective Cognitive Decline ◽  
Preclinical Alzheimer’S Disease

scholarly journals P-tau and neurodegeneration mediate the effect of β-amyloid on cognition in non-demented elders

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Ling-Zhi Ma ◽  
Hao Hu ◽  
Zuo-Teng Wang ◽  
Ya-Nan Ou ◽  
Qiang Dong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Mediating Effect ◽  
Total Effect ◽  
Independent Effect ◽  
Carrier Status ◽  
Mediation Effects ◽  
Β Amyloid ◽  
The Impact

Abstract Background There are many pathological changes in the brains of Alzheimer’s disease (AD) patients. For many years, the mainstream view on the pathogenesis of AD believes that β-amyloid (Aβ) usually acts independently in addition to triggering functions. However, the evidence now accumulating indicates another case that these pathological types have synergies. The objective of this study was to investigate whether effects of Aβ pathology on cognition were mediated by AD pathologies, including tau-related pathology (p-tau), neurodegeneration (t-tau, MRI measurements), axonal injury (NFL), synaptic dysfunction (neurogranin), and neuroinflammation (sTREM2, YKL-40). Methods Three hundred seventy normal controls (CN) and 623 MCI patients from the ADNI (Alzheimer’s Disease Neuroimaging Initiative) database were recruited in this research. Linear mixed-effects models were used to evaluate the associations of baseline Aβ with cognitive decline and biomarkers of several pathophysiological pathways. Causal mediation analyses with 10,000 bootstrapped iterations were conducted to explore the mediation effects of AD pathologies on cognition. Results Tau-related pathology, neurodegeneration, neuroinflammation are correlated with the concentration of Aβ, even in CN participants. The results show that age, gender, and APOE ε4 carrier status have a moderating influence on some of these relationships. There is a stronger association of Aβ with biomarkers and cognitive changes in the elderly and females. In CN group, Aβ pathology is directly related to poor cognition and has no mediating effect (p < 0.05). In mild cognitive impairment, tau-related pathology (26.15% of total effect) and neurodegeneration (14.8% to 47.0% of total effect) mediate the impact of Aβ on cognition. Conclusions In conclusion, early Aβ accumulation has an independent effect on cognitive decline in CN and a tau, neurodegeneration-dependent effect in the subsequent cognitive decline in MCI patients.

scholarly journals Amyloid and tau imaging biomarkers explain cognitive decline from late middle-age

Brain ◽  
2019 ◽  
Vol 143 (1) ◽  
pp. 320-335 ◽  
Author(s):  
Tobey J Betthauser ◽  
Rebecca L Koscik ◽  
Erin M Jonaitis ◽  
Samantha L Allison ◽  
Karly A Cody ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Middle Age ◽  
Neurofibrillary Tangle ◽  
Imaging Biomarkers ◽  
Cognitive Tests ◽  
Preclinical Alzheimer’S Disease ◽  
Significant Group ◽  
Health Factors

Abstract This study investigated differences in retrospective cognitive trajectories between amyloid and tau PET biomarker stratified groups in initially cognitively unimpaired participants sampled from the Wisconsin Registry for Alzheimer’s Prevention. One hundred and sixty-seven initially unimpaired individuals (baseline age 59 ± 6 years; 115 females) were stratified by elevated amyloid-β and tau status based on 11C-Pittsburgh compound B (PiB) and 18F-MK-6240 PET imaging. Mixed effects models were used to determine if longitudinal cognitive trajectories based on a composite of cognitive tests including memory and executive function differed between biomarker groups. Secondary analyses investigated group differences for a variety of cross-sectional health and cognitive tests, and associations between 18F-MK-6240, 11C-PiB, and age. A significant group × age interaction was observed with post hoc comparisons indicating that the group with both elevated amyloid and tau pathophysiology were declining approximately three times faster in retrospective cognition compared to those with just one or no elevated biomarkers. This result was robust against various thresholds and medial temporal lobe regions defining elevated tau. Participants were relatively healthy and mostly did not differ between biomarker groups in health factors at the beginning or end of study, or most cognitive measures at study entry. Analyses investigating association between age, MK-6240 and PiB indicated weak associations between age and 18F-MK-6240 in tangle-associated regions, which were negligible after adjusting for 11C-PiB. Strong associations, particularly in entorhinal cortex, hippocampus and amygdala, were observed between 18F-MK-6240 and global 11C-PiB in regions associated with Braak neurofibrillary tangle stages I–VI. These results suggest that the combination of pathological amyloid and tau is detrimental to cognitive decline in preclinical Alzheimer’s disease during late middle-age. Within the Alzheimer’s disease continuum, middle-age health factors likely do not greatly influence preclinical cognitive decline. Future studies in a larger preclinical sample are needed to determine if and to what extent individual contributions of amyloid and tau affect cognitive decline. 18F-MK-6240 shows promise as a sensitive biomarker for detecting neurofibrillary tangles in preclinical Alzheimer’s disease.

O2-06-04: DOES β-AMYLOID BURDEN PREDICT COGNITIVE DECLINE STATUS IN ADULTS AT RISK FOR ALZHEIMER'S DISEASE?

2006 ◽  
Vol 14 (7S_Part_11) ◽  
pp. P632-P634
Author(s):  
Heather L. Shouel ◽  
Rebecca L. Koscik ◽  
Lindsay R. Clark ◽  
Sara Elizabeth Berman ◽  
Brad T. Christian ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
At Risk ◽  
Cognitive Decline ◽  
Amyloid Burden ◽  
Β Amyloid

FINANCIAL MANAGEMENT SKILLS IN AGING, MCI AND DEMENTIA: CROSS SECTIONAL RELATIONSHIP TO 18F-FLORBETAPIR PET CORTICAL Β-AMYLOID DEPOSITION

2019 ◽  
pp. 1-9
Author(s):  
S. Tolbert ◽  
Y. Liu ◽  
C. Hellegers ◽  
J.R. Petrella ◽  
M.W. Weiner ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
At Risk ◽  
Amyloid Deposition ◽  
Cross Sectional ◽  
Cognitively Normal ◽  
Financial Capacity ◽  
Cohen’S D ◽  
Β Amyloid ◽  
Cohen's D

Background: There is a need to more fully characterize financial capacity losses in the preclinical and prodromal stages of Alzheimer’s disease (AD) and their pathological substrates. Objectives: To test the association between financial skills and cortical β-amyloid deposition in aging and subjects at risk for AD. Design: Cross-sectional analyses of data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI-3) study conducted across 50 plus sites in the US and Canada. Setting: Multicenter biomarker study. Participants: 243 subjects (144 cognitively normal, 79 mild cognitive impairment [MCI], 20 mild AD). Measurements: 18F-Florbetapir brain PET scans to measure global cortical β-amyloid deposition (SUVr) and the Financial Capacity Instrument Short Form (FCI-SF) to evaluate an individual’s financial skills in monetary calculation, financial concepts, checkbook/register usage, and bank statement usage. There are five sub scores and a total score (range of 0–74) with higher scores indicating better financial skill. Results: FCI-SF total score was significantly worse in MCI [Cohen’s d= 0.9 (95%CI: 0.6-1.2)] and AD subjects [Cohen’s d=3.1(CI: 2.5-3.7)] compared to normals. Domain scores and completion times also showed significant difference. Across all subjects, higher cortical β-amyloid SUVr was significantly associated with worse FCI-SF total score after co-varying for age, education, and cognitive score [Cohen’s f2=0.751(CI: 0.5-1.1)]. In cognitively normal subjects, after covarying for age, gender, and education, higher β -amyloid PET SUVr was associated with longer task completion time [Cohen’s f2=0.198(CI: 0.06-0.37)]. Conclusion: Using a multicenter study sample, we document that financial capacity is impaired in the prodromal and mild stages of AD and that such impairments are, in part, associated with the extent of cortical β-amyloid deposition. In normal aging, β-amyloid deposition is associated with slowing of financial tasks. These data confirm and extend prior research highlighting the utility of financial capacity assessments in at risk samples.

Naturally Occurring Antibodies to Tau Exists in Human Blood and Are Not Changed in Alzheimer’s Disease

2020 ◽  
Vol 37 (4) ◽  
pp. 1029-1035 ◽  
Author(s):  
Zhong-Yuan Yu ◽  
Wei-Wei Li ◽  
Hai-Mei Yang ◽  
Noralyn B. Mañucat-Tan ◽  
Jun Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Blood ◽  
Naturally Occurring ◽  
Naturally Occurring Antibodies

P1-071: Genetic and imaging biomarkers predicting beta-amyloid amyloid-related cognitive decline using the Alzheimer's Disease Neuroimaging Initiative data

2013 ◽  
Vol 9 ◽  
pp. P178-P178 ◽  
Author(s):  
Sheng Feng ◽  
Jeff Sevigny ◽  
Ajay Verma ◽  
Donald Bennett ◽  
Yen Ying Lim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Beta Amyloid ◽  
Imaging Biomarkers

scholarly journals Predictors of rapid cognitive decline in Alzheimer's disease: results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing

2011 ◽  
Vol 24 (2) ◽  
pp. 197-204 ◽  
Author(s):  
Alessandro Sona ◽  
Ping Zhang ◽  
David Ames ◽  
Ashley I. Bush ◽  
Nicola T. Lautenschlager ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Rating Scale ◽  
Cognitive Status ◽  
Imaging Biomarkers ◽  
Clinical Dementia Rating ◽  
Factors Associated ◽  
Biological Variables ◽  
Rapid Cognitive Decline

ABSTRACTBackground: The AIBL study, which commenced in November 2006, is a two-center prospective study of a cohort of 1112 volunteers aged 60+. The cohort includes 211 patients meeting NINCDS-ADRDA criteria for Alzheimer's disease (AD) (180 probable and 31 possible). We aimed to identify factors associated with rapid cognitive decline over 18 months in this cohort of AD patients.Methods: We defined rapid cognitive decline as a drop of 6 points or more on the Mini-Mental State Examination (MMSE) between baseline and 18-month follow-up. Analyses were also conducted with a threshold of 4, 5, 7 and 8 points, as well as with and without subjects who had died or were too severely affected to be interviewed at 18 months and after, both including and excluding subjects whose AD diagnosis was “possible” AD. We sought correlations between rapid cognitive decline and demographic, clinical and biological variables.Results: Of the 211 AD patients recruited at baseline, we had available data for 156 (73.9%) patients at 18 months. Fifty-one patients were considered rapid cognitive decliners (32.7%). A higher Clinical Dementia Rating scale (CDR) and higher CDR “sum of boxes” score at baseline were the major predictors of rapid cognitive decline in this population. Furthermore, using logistic regression model analysis, patients treated with a cholinesterase inhibitor (CheI) had a higher risk of being rapid cognitive decliners, as did males and those of younger age.Conclusions: Almost one third of patients satisfying established research criteria for AD experienced rapid cognitive decline. Worse baseline functional and cognitive status and treatment with a CheI were the major factors associated with rapid cognitive decline over 18 months in this population.

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