Sequence of Alzheimer disease biomarker changes in cognitively normal adults: A cross-sectional study
| Autor: | Parinaz Massoumzadeh, Randall J. Bateman, John C. Morris, Colin L. Masters, Hiroshi Mori, Eric McDade, Peter R. Schofield, Carlos Cruchaga, Mathias Jucker, Richard J. Perrin, Tammie L.S. Benzinger, Jasmeer P. Chhatwal, Jonathan Vöglein, Jason Hassenstab, Elizabeth A. Grant, Chengjie Xiong, Neill R. Graff-Radford, Jingqin Luo, Marilyn S. Albert, Folasade Agboola, Anne M. Fagan, Bernardino Ghetti, Sterling C. Johnson |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology Male physiopathology [Cognitive Dysfunction] pathology [Cognitive Dysfunction] diagnostic imaging [Cognitive Dysfunction] 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole Hippocampus cerebrospinal fluid [Amyloid beta-Peptides] chemistry.chemical_compound pathology [Alzheimer Disease] metabolism [Cognitive Dysfunction] 0302 clinical medicine diagnostic imaging [Cerebral Cortex] Cognitive decline skin and connective tissue diseases Cerebral Cortex Aged 80 and over diagnostic imaging [Hippocampus] Aniline Compounds medicine.diagnostic_test Age Factors Middle Aged amyloid beta-protein (1-42) Magnetic Resonance Imaging Biomarker (medicine) Female Alzheimer's disease metabolism [Alzheimer Disease] metabolism [Biomarkers] Adult medicine.medical_specialty Adolescent metabolism [Amyloid beta-Peptides] Prodromal Symptoms Standardized uptake value MAPT protein human tau Proteins Neuropathology physiopathology [Alzheimer Disease] Article 03 medical and health sciences Young Adult Alzheimer Disease Internal medicine medicine Humans Cognitive Dysfunction ddc:610 cerebrospinal fluid [Peptide Fragments] Aged Amyloid beta-Peptides business.industry Magnetic resonance imaging amyloid beta-protein (1-40) medicine.disease Peptide Fragments Thiazoles 030104 developmental biology Cross-Sectional Studies pathology [Hippocampus] chemistry cerebrospinal fluid [tau Proteins] Positron-Emission Tomography pathology [Cerebral Cortex] sense organs Neurology (clinical) business Pittsburgh compound B diagnostic imaging [Alzheimer Disease] 030217 neurology & neurosurgery Biomarkers |
| Zdroj: | Neurology 95(23), e3104-e3116 (2020). doi:10.1212/WNL.0000000000010747 Neurology |
| Popis: | ObjectiveTo determine the ordering of changes in Alzheimer disease (AD) biomarkers among cognitively normal individuals.MethodsCross-sectional data, including CSF analytes, molecular imaging of cerebral fibrillar β-amyloid (Aβ) with PET using the [11C] benzothiazole tracer Pittsburgh compound B (PiB), MRI-based brain structures, and clinical/cognitive outcomes harmonized from 8 studies, collectively involving 3,284 cognitively normal individuals 18 to 101 years of age, were analyzed. The age at which each marker exhibited an accelerated change (called the change point) was estimated and compared across the markers.ResultsAccelerated changes in CSF Aβ1-42 (Aβ42) occurred at 48.28 years of age and in Aβ42/Aβ40 ratio at 46.02 years, followed by PiB mean cortical standardized uptake value ratio (SUVR) with a change point at 54.47 years. CSF total tau (Tau) and tau phosphorylated at threonine 181 (Ptau) had a change point at ≈60 years, similar to those for MRI hippocampal volume and cortical thickness. The change point for a cognitive composite occurred at 62.41 years. The change points for CSF Aβ42 and Aβ42/Aβ40 ratio, albeit not significantly different from that for PiB SUVR, occurred significantly earlier than that for CSF Tau, Ptau, MRI markers, and the cognitive composite. Adjusted analyses confirmed that accelerated changes in CSF Tau, Ptau, MRI markers, and the cognitive composite occurred at ages not significantly different from each other.ConclusionsOur findings support the hypothesized early changes of amyloid in preclinical AD and suggest that changes in neuronal injury and neurodegeneration markers occur close in time to cognitive decline. |
| Databáze: | OpenAIRE |
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