Journal Article

DZNE-2020-06692

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Neurogenetic contributions to amyloid beta and tau spreading in the human cortex.

Sepulcre, J. (Corresponding author) ; Grothe, M. J.DZNE* ; d'Oleire Uquillas, F. ; Ortiz-Terán, L. ; Diez, I. ; Yang, H.-S. ; Jacobs, H. I. L. ; Hanseeuw, B. J. ; Li, Q. ; El-Fakhri, G. ; Sperling, R. A. ; Johnson, K. A.

2018
Nature America Inc. New York, NY

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Please use a persistent id in citations: doi:10.1038/s41591-018-0206-4

Abstract: Tau and amyloid beta (Aβ) proteins accumulate along neuronal circuits in Alzheimer's disease. Unraveling the genetic background for the regional vulnerability of these proteinopathies can help in understanding the mechanisms of pathology progression. To that end, we developed a novel graph theory approach and used it to investigate the intersection of longitudinal Aβ and tau positron emission tomography imaging of healthy adult individuals and the genetic transcriptome of the Allen Human Brain Atlas. We identified distinctive pathways for tau and Aβ accumulation, of which the tau pathways correlated with cognitive levels. We found that tau propagation and Aβ propagation patterns were associated with a common genetic profile related to lipid metabolism, in which APOE played a central role, whereas the tau-specific genetic profile was classified as 'axon related' and the Aβ profile as 'dendrite related'. This study reveals distinct genetic profiles that may confer vulnerability to tau and Aβ in vivo propagation in the human brain.

Keyword(s): Alzheimer Disease: diagnostic imaging (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Amyloid beta-Peptides: genetics (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Brain: diagnostic imaging (MeSH) ; Cerebral Cortex: diagnostic imaging (MeSH) ; Cerebral Cortex: pathology (MeSH) ; Female (MeSH) ; Humans (MeSH) ; Lipid Metabolism: genetics (MeSH) ; Male (MeSH) ; Positron-Emission Tomography (MeSH) ; Protein Aggregation, Pathological: diagnostic imaging (MeSH) ; Protein Aggregation, Pathological: genetics (MeSH) ; Protein Aggregation, Pathological: pathology (MeSH) ; Transcriptome: genetics (MeSH) ; tau Proteins: genetics (MeSH) ; tau Proteins: metabolism (MeSH) ; Amyloid beta-Peptides ; tau Proteins

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Contributing Institute(s):

1. Clinical Dementia Research (Rostock /Greifswald) (AG Teipel)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2018

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 80 ; JCR ; Nationallizenz ; SCOPUS ; Web of Science Core Collection

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