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Blood Markers in Healthy-Aged Nonagenarians: A Combination of High Telomere Length and Low Amyloidβ Are Strongly Associated With Healthy Aging in the Oldest Old

Published on Nov 28, 2018in Frontiers in Aging Neuroscience 3.63
· DOI :10.3389/fnagi.2018.00380
Gorka Fernández-Eulate , Ainhoa Alberro2
Estimated H-index: 2
+ 19 AuthorsAdolfo López de Munain33
Estimated H-index: 33
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Abstract
Many factors may converge in healthy ageing in the oldest old, but their association and predictive power on healthy o functionally impaired ageing has yet to be demonstrated. By detecting healthy ageing and in turn, poor ageing, we could take action to prevent chronic diseases associated with age. We conducted a pilot study comparing results of a set of markers (peripheral blood mononuclear cell telomere length or PBMC, circulating Aβ peptides, anti-Aβ antibodies, and ApoE status) previously associated with poor ageing or cognitive deterioration, and their combinations, in a cohort of “neurologically healthy” (both motor and cognitive) nonagenarians (n=20) and functionally impaired, institutionalized nonagenarians (n=38) recruited between 2014 and 2015. We recruited 58 nonagenarians (41 women, 70.7%; mean age: 92.37 years in the neurologically healthy group vs 94.13 years in the functionally impaired group). Healthy nonagenarians had significantly higher mean PBMC telomere lengths (mean=7, p=0.001), this being inversely correlated with functional impairment, and lower circulating Aβ40 (total in plasma fraction or TP and free in plasma fraction or FP), Aβ42 (TP and FP) and Aβ17 (FP) levels (FP40 131.35, p=0.004; TP40 299.10, p=0.007; FP42 6.29, p=0.009; TP42 22.53, p=0.019; FP17 1.32 p=0.001; TP17 4.47, p=0.3), after adjusting by age. Although healthy nonagenarians had higher anti-Aβ40 antibodies levels (net adsorbed signal or NAS +/- SD: 0.211 +/- 0.107), the number of participants that pass the threshold (NAS>3) to be considered as positive did not show such a strong association. There was no association with ApoE status. Additionally, we propose a “Composite Neurologically Healthy Ageing Score” combining TP40 and mean telomere length, the strongest correlation of measured biomarkers with neurologically healthy status in nonagenarians (AUC=0.904).
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References64
Newest
Published on Dec 1, 2018in Alzheimer's Research & Therapy
Ana-María Lacosta3
Estimated H-index: 3
,
María Pascual-Lucas2
Estimated H-index: 2
+ 17 AuthorsInmaculada Monleón11
Estimated H-index: 11
Background Immunotherapy targeting the amyloid-β (Aβ) peptide is a promising strategy for the treatment of Alzheimer’s disease (AD); however, none of the active or passive vaccines tested have been demonstrated to be effective to date. We have developed the first active vaccine against the C-terminal end of Aβ40, ABvac40, and assessed its safety and tolerability in a phase I clinical trial.
5 Citations Source Cite
Published on Feb 1, 2018in Biological Psychiatry 11.50
Christopher H. van Dyck45
Estimated H-index: 45
(Yale University)
Abstract The majority of putative disease-modifying treatments in development for Alzheimer’s disease are directed against the amyloid-β (Aβ) peptide. Among the anti-Aβ therapeutic approaches, the most extensively developed is immunotherapy—specifically, passive immunization through administration of exogenous monoclonal antibodies (mAbs). Although testing of mAbs has been fraught with failure and confusing results, the experience gained from these trials has provided important clues for better ...
43 Citations Source Cite
Published on Feb 1, 2018in Movement Disorders 8.06
Jennifer G. Goldman28
Estimated H-index: 28
,
Howard F. Andrews52
Estimated H-index: 52
+ 17 AuthorsPaul Tuite33
Estimated H-index: 33
Objective: Examine relationships among neurodegenerative biomarkers and PD motor and nonmotor symptoms. Background: CSF alpha-synuclein is decreased in PD versus healthy controls, but whether plasma and saliva alpha-synuclein differentiate these groups is controversial. Correlations of alpha-synuclein among biofluids (CSF, plasma, saliva) or biomarkers (eg, beta-amyloid, tau [total, phosphorylated]) are not fully understood. The relationships of these biomarkers with PD clinical features remain ...
22 Citations Source Cite
Published on Feb 1, 2018in Nature 43.07
Akinori Nakamura42
Estimated H-index: 42
,
Naoki Kaneko5
Estimated H-index: 5
+ 17 AuthorsChristopher C. Rowe72
Estimated H-index: 72
Measurement of human plasma amyloid-β biomarkers using immunoprecipitation coupled with mass spectrometry reliably predicts individual brain amyloid-β status and has potential clinical utility.
117 Citations Source Cite
Published on Sep 5, 2017in Neurology 8.69
Yen Ying Lim22
Estimated H-index: 22
,
Elizabeth C. Mormino33
Estimated H-index: 33
Objective: To clarify associations between APOE e4 allele and age on longitudinal rates of β-amyloid (Aβ) accumulation within Aβ+ and Aβ− older individuals without dementia. Methods: We analyzed 595 older adults without dementia classified cross-sectionally as Aβ− (n = 325) and Aβ+ (n = 270) using longitudinal florbetapir PET. The influence of age and APOE genotype on longitudinal accumulation of Aβ was examined with linear mixed models. Results: APOE e4 and older age were associated with higher...
19 Citations Source Cite
Published on Aug 1, 2017in Alzheimers & Dementia 14.42
Vitaliy Ovod10
Estimated H-index: 10
(WashU: Washington University in St. Louis),
Kara Ramsey1
Estimated H-index: 1
(WashU: Washington University in St. Louis)
+ 11 AuthorsJohn C. Morris141
Estimated H-index: 141
(WashU: Washington University in St. Louis)
Abstract Introduction Cerebrospinal fluid analysis and other measurements of amyloidosis, such as amyloid-binding positron emission tomography studies, are limited by cost and availability. There is a need for a more practical amyloid β (Aβ) biomarker for central nervous system amyloid deposition. Methods We adapted our previously reported stable isotope labeling kinetics protocol to analyze the turnover kinetics and concentrations of Aβ38, Aβ40, and Aβ42 in human plasma. Results Aβ isoforms hav...
57 Citations Source Cite
Published on May 2, 2017in Neurology 8.69
Norman Relkin44
Estimated H-index: 44
(Cornell University),
Ronald G. Thomas52
Estimated H-index: 52
(UCSD: University of California, San Diego)
+ 11 AuthorsRema Raman45
Estimated H-index: 45
(SC: University of Southern California)
Objective: We tested biweekly infusions of IV immunoglobulin (IVIg) as a possible treatment for mild to moderate Alzheimer disease (AD) dementia. Methods: In a phase 3, double-blind, placebo-controlled trial, we randomly assigned 390 participants with mild to moderate AD to receive placebo (low-dose albumin) or IVIg (Gammagard Liquid; Baxalta, Bannockburn, IL) administered IV at doses of 0.2 or 0.4 g/kg every 2 weeks for 18 months. The primary cognitive outcome was change from baseline to 18 mon...
31 Citations Source Cite
Published on Feb 1, 2017in Journal of Neurology, Neurosurgery, and Psychiatry 8.27
Shawn Kile2
Estimated H-index: 2
,
William J. Au2
Estimated H-index: 2
+ 5 AuthorsAzad Ghassemi1
Estimated H-index: 1
Objective To determine the effect of intravenous immunoglobulin (IVIG) on brain atrophy and cognitive function in mild cognitive impairment (MCI) due to Alzheimer9s disease (AD). Methods 50 participant 50–84 years of age with amnestic MCI were administered 0.4 g/kg 10% IVIG or 0.9% saline every 2 weeks for a total of 5 infusions (2 g/kg total dose) in a randomised double-blinded design. MRI brain was completed at baseline, 12 and 24 months. Cognitive testing was completed at baseline and every 4...
18 Citations Source Cite
Published on Jan 1, 2017in Molecular Psychiatry 11.97
André Lacour11
Estimated H-index: 11
,
Anna Espinosa4
Estimated H-index: 4
+ 36 AuthorsAna Mauleón13
Estimated H-index: 13
Genome-wide significant risk factors for Alzheimer’s disease: role in progression to dementia due to Alzheimer's disease among subjects with mild cognitive impairment
31 Citations Source Cite
Published on Jan 1, 2017in International Review of Neurobiology 2.55
Iskandar Johar3
Estimated H-index: 3
('KCL': King's College London),
Brit Mollenhauer45
Estimated H-index: 45
(GAU: University of Göttingen),
Dag Aarsland88
Estimated H-index: 88
('KCL': King's College London)
Abstract Among the nonmotor symptoms in Parkinson's disease (PD), cognitive impairment is one of the most common and devastating. Over recent years, mild cognitive impairment (MCI) has become a recognized feature of PD (PD-MCI). The underlying mechanisms which influence onset, rate of decline, and conversion to dementia (PDD) are largely unknown. Adding to this uncertainty is the heterogeneity of cognitive domains affected. Currently there are no disease-modifying treatments that can slow or rev...
9 Citations Source Cite
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Published on Jun 1, 2019in Ageing Research Reviews 10.39
Aline Carla Araújo Carvalho (UFS: Universidade Federal de Sergipe), Mário Luis Tavares Mendes (UFS: Universidade Federal de Sergipe)+ 3 AuthorsPaulo Ricardo Saquete Martins-Filho11
Estimated H-index: 11
(UFS: Universidade Federal de Sergipe)
Abstract Telomere shortening has been proposed as a potentially useful biomarker of human ageing and age-related morbidity and mortality. We performed a systematic review and meta-analysis to summarize results from individual studies on the telomere length according to the frailty status and frailty index in older adults. We searched the PubMed, SCOPUS and Web of Science databases to identify studies that evaluated the telomere length in frail and non-frail older adults and the relationship betw...
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