Plasma Exosomal miRNAs in Persons with and without Alzheimer Disease: Altered Expression and Prospects for Biomarkers

PLoS ONE, Journal Year: 2015, Volume and Issue: 10(10), P. e0139233 - e0139233

Published: Oct. 1, 2015

To assess the value of exosomal miRNAs as biomarkers for Alzheimer disease (AD), expression microRNAs was measured in a plasma fraction enriched exosomes by differential centrifugation, using Illumina deep sequencing. Samples from 35 persons with clinical diagnosis AD dementia were compared to age and sex matched controls. Although these samples contained less than 0.1 microgram total RNA, sequencing gave reliable informative results. Twenty showed significant differences group initial screening (miR-23b-3p, miR-24-3p, miR-29b-3p, miR-125b-5p, miR-138-5p, miR-139-5p, miR-141-3p, miR-150-5p, miR-152-3p, miR-185-5p, miR-338-3p, miR-342-3p, miR-342-5p, miR-548at-5p, miR-659-5p, miR-3065-5p, miR-3613-3p, miR-3916, miR-4772-3p, miR-5001-3p), many which satisfied additional biological statistical criteria, among panel seven highly machine learning model predicting status individual 83–89% accuracy. This performance is not due over-fitting, because a) we used separate training testing, b) similar achieved when tested on technical replicate data. Perhaps most interesting single miRNA expressed at about 60% control levels, correlated several other that significantly down-regulated AD, c) also reported be two previous studies. The findings warrant replication follow-up larger cohort patients controls who have been carefully characterized terms cognitive imaging data, (e.g., CSF amyloid tau levels) risk factors apoE4 status), are sampled repeatedly over time. Integrating data likely provide robust disease.

Language: Английский

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Amyloid β-based therapy for Alzheimer’s disease: challenges, successes and future

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: June 30, 2023

Abstract Amyloid β protein (Aβ) is the main component of neuritic plaques in Alzheimer’s disease (AD), and its accumulation has been considered as molecular driver pathogenesis progression. Aβ prime target for development AD therapy. However, repeated failures Aβ-targeted clinical trials have cast considerable doubt on amyloid cascade hypothesis whether drug followed correct course. recent successes targeted assuaged those doubts. In this review, we discussed evolution over last 30 years summarized application diagnosis modification. particular, extensively pitfalls, promises important unanswered questions regarding current anti-Aβ therapy, well strategies further study more feasible approaches optimization prevention treatment.

Language: Английский

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Imaging tau and amyloid-β proteinopathies in Alzheimer disease and other conditions

Nature Reviews Neurology, Journal Year: 2018, Volume and Issue: 14(4), P. 225 - 236

Published: Feb. 16, 2018

Language: Английский

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Neurofilament Light Chain in Blood and CSF as Marker of Disease Progression in Mouse Models and in Neurodegenerative Diseases

Neuron, Journal Year: 2016, Volume and Issue: 91(1), P. 56 - 66

Published: June 11, 2016

Language: Английский

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Age, Sex, andAPOEε4 Effects on Memory, Brain Structure, and β-Amyloid Across the Adult Life Span

JAMA Neurology, Journal Year: 2015, Volume and Issue: 72(5), P. 511 - 511

Published: March 16, 2015

Typical cognitive aging may be defined as age-associated changes in performance individuals who remain free of dementia. Ideally, the full adult age spectrum should included to assess brain imaging findings associated with typical aging.To compare age, sex, and APOE ε4 effects on memory, structure (adjusted hippocampal volume [HVa]), amyloid positron emission tomography (PET) cognitively normal aged 30 95 years old.Cross-sectional observational study (March 2006 October 2014) at an academic medical center. We studied 1246 individuals, including 1209 participants 50 old enrolled a population-based 37 self-selected volunteers 49 old.Memory, HVa, PET.Overall, memory worsened from through 90s. The HVa gradually mid-60s more steeply beyond that age. median PET was low until 70 increased thereafter. Memory worse men than women overall (P < .001) specifically 40 years. lower 60 There no sex difference any Within each were not different by status From onward, carriers had significantly greater noncarriers. However, ages which 10% population positive 57 for 64 noncarriers.Male is among while not. In contrast, (from onward), Worsening occur earlier abnormal PET. Therefore, neuropathological processes other β-amyloidosis must underlie declines function middle Our are consistent model late-onset Alzheimer disease arises later life background preexisting structural decline β-amyloid deposits.

Language: Английский

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