Detection of β-amyloid positivity in Alzheimer’s Disease Neuroimaging Initiative participants with demographics, cognition, MRI and plasma biomarkers
Duygu Tosun,Duygu Tosun,Dallas P. Veitch,Paul S. Aisen,Clifford R. Jack,William J. Jagust,Ronald C. Petersen,Andrew J. Saykin,James G. Bollinger,Vitaliy Ovod,Kwasi G. Mawuenyega,Randall J. Bateman,Leslie M. Shaw,John Q. Trojanowski,Kaj Blennow,Kaj Blennow,Henrik Zetterberg,Michael W. Weiner,Michael W. Weiner +18 more
- Vol. 3, Iss: 2
TLDR
In this paper, the authors used multidisciplinary data from cognitively unimpaired participants and participants with mild cognitive impairment recruited by the multisite biomarker study of Alzheimer's Disease Neuroimaging Initiative, and found that when combined with clinical information, such as demographic data, APOE genotype, cognitive assessments and MRI can assist plasma biomarkers in detecting β-amyloid-positivity.Abstract:
In vivo gold standard for the ante-mortem assessment of brain β-amyloid pathology is currently β-amyloid positron emission tomography or cerebrospinal fluid measures of β-amyloid42 or the β-amyloid42/β-amyloid40 ratio The widespread acceptance of a biomarker classification scheme for the Alzheimer's disease continuum has ignited interest in more affordable and accessible approaches to detect Alzheimer's disease β-amyloid pathology, a process that often slows down the recruitment into, and adds to the cost of, clinical trials Recently, there has been considerable excitement concerning the value of blood biomarkers Leveraging multidisciplinary data from cognitively unimpaired participants and participants with mild cognitive impairment recruited by the multisite biomarker study of Alzheimer's Disease Neuroimaging Initiative, here we assessed to what extent plasma β-amyloid42/β-amyloid40, neurofilament light and phosphorylated-tau at threonine-181 biomarkers detect the presence of β-amyloid pathology, and to what extent the addition of clinical information such as demographic data, APOE genotype, cognitive assessments and MRI can assist plasma biomarkers in detecting β-amyloid-positivity Our results confirm plasma β-amyloid42/β-amyloid40 as a robust biomarker of brain β-amyloid-positivity (area under curve, 080-087) Plasma phosphorylated-tau at threonine-181 detected β-amyloid-positivity only in the cognitively impaired with a moderate area under curve of 067, whereas plasma neurofilament light did not detect β-amyloid-positivity in either group of participants Clinical information as well as MRI-score independently detected positron emission tomography β-amyloid-positivity in both cognitively unimpaired and impaired (area under curve, 069-081) Clinical information, particularly APOE e4 status, enhanced the performance of plasma biomarkers in the detection of positron emission tomography β-amyloid-positivity by 006-014 units of area under curve for cognitively unimpaired, and by 021-025 units for cognitively impaired; and further enhancement of these models with an MRI-score of β-amyloid-positivity yielded an additional improvement of 004-011 units of area under curve for cognitively unimpaired and 005-009 units for cognitively impaired Taken together, these multi-disciplinary results suggest that when combined with clinical information, plasma phosphorylated-tau at threonine-181 and neurofilament light biomarkers, and an MRI-score could effectively identify β-amyloid+ cognitively unimpaired and impaired (area under curve, 080-090) Yet, when the MRI-score is considered in combination with clinical information, plasma phosphorylated-tau at threonine-181 and plasma neurofilament light have minimal added value for detecting β-amyloid-positivity Our systematic comparison of β-amyloid-positivity detection models identified effective combinations of demographics, APOE, global cognition, MRI and plasma biomarkers Promising minimally invasive and low-cost predictors such as plasma biomarkers of β-amyloid42/β-amyloid40 may be improved by age and APOE genotyperead more
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Revisiting the grammar of Tau aggregation and pathology formation: how new insights from brain pathology are shaping how we study and target Tauopathies
TL;DR: In this paper , the authors discuss the importance of adopting new experimental approaches that embrace the complexity of Tau aggregation and pathology as an important first step towards developing mechanism-and structure-based therapies that account for the pathological and clinical heterogeneity of Alzheimer's disease and Tauopathies.
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Selective reduction of astrocyte apoE3 and apoE4 strongly reduces Aβ accumulation and plaque-related pathology in a mouse model of amyloidosis
TL;DR: In this paper , a tamoxifen-inducible APOE removal from astrocytes was shown to significantly reduce the accumulation of Aβ peptide into amyloid plaques.
Journal ArticleDOI
Blood biomarkers for the diagnosis of amnestic mild cognitive impairment and Alzheimer's disease: A systematic review and meta-analysis.
Yi Qu,Ya-Hui Ma,Yu-Yuan Huang,Ya-Nan Ou,Xue-Ning Shen,Shi-Dong Chen,Qiang Dong,Lan Tan,Jin-Tai Yu +8 more
TL;DR: Wang et al. as discussed by the authors evaluated the effects of blood-based biomarkers of Alzheimer's disease on blood, and systematical searched Embase, PubMed and Cochrane for eligible studies, which demonstrated T-tau (average ratio: 1.25-1.62) increased, and AβPPr (0.65-0.88) decreased from controls to amnestic mild cognitive impairment (aMCI) to AD.
Journal ArticleDOI
Using the Alzheimer's Disease Neuroimaging Initiative to improve early detection, diagnosis, and treatment of Alzheimer's disease.
Dallas P. Veitch,Michael W. Weiner,Paul S. Aisen,Laurel A. Beckett,Charles DeCarli,Robert C. Green,Danielle J Harvey,Clifford R. Jack,William J. Jagust,Susan M. Landau,John C. Morris,Ozioma C. Okonkwo,Richard J. Perrin,Ronald C. Petersen,Monica Rivera-Mindt,Andrew J. Saykin,Leslie M. Shaw,Arthur W. Toga,Duygu Tosun,John Q. Trojanowski,Alzheimer’s Disease Neuroimaging Initiative +20 more
TL;DR: The Alzheimer's Disease Neuroimaging Initiative (ADNI) has accumulated 15 years of clinical, neuroimaging, cognitive, bio-fluid biomarker and genetic data, and biofluid samples available to researchers, resulting in more than 3500 publications as discussed by the authors.
Journal ArticleDOI
Selective reduction of astrocyte apoE3 and apoE4 strongly reduces Aβ accumulation and plaque-related pathology in a mouse model of amyloidosis
TL;DR: In this paper , a tamoxifen-inducible APOE removal from astrocytes was shown to significantly reduce the accumulation of Aβ peptide into amyloid plaques.
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