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Cognitively unimpai...
Cognitively unimpaired individuals with a low burden of A beta pathology have a distinct CSF biomarker profile
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Mila-Aloma, M. (author)
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Shekari, M. (author)
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Salvado, G. (author)
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Gispert, J. D. (author)
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Arenaza-Urquijo, E. M. (author)
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Operto, G. (author)
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Falcon, C. (author)
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Vilor-Tejedor, N. (author)
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Grau-Rivera, O. (author)
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Sala-Vila, A. (author)
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Sanchez-Benavides, G. (author)
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Gonzalez-de-Echavarri, J. M. (author)
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Minguillon, C. (author)
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Fauria, K. (author)
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Ninerola-Baizan, A. (author)
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Perissinotti, A. (author)
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Simon, M. (author)
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Kollmorgen, G. (author)
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Blennow, Kaj, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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Suarez-Calvet, M. (author)
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Molinuevo, J. L. (author)
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(creator_code:org_t)
- 2021-07-27
- 2021
- English.
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In: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 13:1
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https://alzres.biome...
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Abstract
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- Background: Understanding the changes that occur in the transitional stage between absent and overt amyloid-beta (A beta) pathology within the Alzheimer's continuum is crucial to develop therapeutic and preventive strategies. The objective of this study is to test whether cognitively unimpaired individuals with a low burden of A beta pathology have a distinct CSF, structural, and functional neuroimaging biomarker profile. Methods: Cross-sectional study of 318 middle-aged, cognitively unimpaired individuals from the ALFA+ cohort. We measured CSF A beta 42/40, phosphorylated tau (p-tau), total tau (t-tau), neurofilament light (NfL), neurogranin, sTREM2, YKL40, GFAP, IL6, S100B, and alpha-synuclein. Participants also underwent cognitive assessments, APOE genotyping, structural MRI, [F-18]-FDG, and [F-18]-flutemetamol PET. To ensure the robustness of our results, we used three definitions of low burden of A beta pathology: (1) positive CSF A beta 42/40 and < 30 Centiloids in A beta PET, (2) positive CSF A beta 42/40 and negative A beta PET visual read, and (3) 20-40 Centiloid range in A beta PET. We tested CSF and neuroimaging biomarker differences between the low burden group and the corresponding A beta-negative group, adjusted by age and sex. Results: The prevalence and demographic characteristics of the low burden group differed between the three definitions. CSF p-tau and t-tau were increased in the low burden group compared to the A beta-negative in all definitions. CSF neurogranin was increased in the low burden group definitions 1 and 3, while CSF NfL was only increased in the low burden group definition 1. None of the defined low burden groups showed signs of atrophy or glucose hypometabolism. Instead, we found slight increases in cortical thickness and metabolism in definition 2. Conclusions: There are biologically meaningful A beta-downstream effects in individuals with a low burden of A beta pathology, while structural and functional changes are still subtle or absent. These findings support considering individuals with a low burden of A beta pathology for clinical trials.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Preclinical
- Alzheimer's disease
- CSF
- Biomarkers
- Subthreshold
- Cognitively unimpaired
- fluid amyloid-beta
- alzheimers-disease
- neurodegeneration
- definition
- deposition
- Neurosciences & Neurology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Mila-Aloma, M.
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Shekari, M.
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Salvado, G.
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Gispert, J. D.
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Arenaza-Urquijo, ...
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Operto, G.
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show more...
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Falcon, C.
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Vilor-Tejedor, N ...
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Grau-Rivera, O.
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Sala-Vila, A.
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Sanchez-Benavide ...
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Gonzalez-de-Echa ...
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Minguillon, C.
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Fauria, K.
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Ninerola-Baizan, ...
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Perissinotti, A.
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Simon, M.
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Kollmorgen, G.
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Zetterberg, Henr ...
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Blennow, Kaj, 19 ...
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Suarez-Calvet, M ...
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Molinuevo, J. L.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Alzheimers Resea ...
- By the university
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University of Gothenburg