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Microglial activation and tau propagate jointly across Braak stages.

Pascoal, Tharick A (author)
Benedet, Andrea L (author)
Ashton, Nicholas J. (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Kang, Min Su (author)
Therriault, Joseph (author)
Chamoun, Mira (author)
Savard, Melissa (author)
Lussier, Firoza Z (author)
Tissot, Cécile (author)
Karikari, Thomas (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Ottoy, Julie (author)
Mathotaarachchi, Sulantha (author)
Stevenson, Jenna (author)
Massarweh, Gassan (author)
Schöll, Michael, 1980 (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Wallenberg Centre for Molecular and Translational Medicine,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
de Leon, Mony J (author)
Soucy, Jean-Paul (author)
Edison, Paul (author)
Blennow, Kaj, 1958 (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Zetterberg, Henrik, 1973 (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Gauthier, Serge (author)
Rosa-Neto, Pedro (author)
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 (creator_code:org_t)
2021-08-26
2021
English.
In: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 27, s. 1592-1599
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Compelling experimental evidence suggests that microglial activation is involved in the spread of tau tangles over the neocortex in Alzheimer's disease (AD). We tested the hypothesis that the spatial propagation of microglial activation and tau accumulation colocalize in a Braak-like pattern in the living human brain. We studied 130 individuals across the aging and AD clinical spectrum with positron emission tomography brain imaging for microglial activation ([11C]PBR28), amyloid-β (Aβ) ([18F]AZD4694) and tau ([18F]MK-6240) pathologies. We further assessed microglial triggering receptor expressed on myeloid cells 2 (TREM2) cerebrospinal fluid (CSF) concentrations and brain gene expression patterns. We found that [11C]PBR28 correlated with CSF soluble TREM2 and showed regional distribution resembling TREM2 gene expression. Network analysis revealed that microglial activation and tau correlated hierarchically with each other following Braak-like stages. Regression analysis revealed that the longitudinal tau propagation pathways depended on the baseline microglia network rather than the tau network circuits. The co-occurrence of Aβ, tau and microglia abnormalities was the strongest predictor of cognitive impairment in our study population. Our findings support a model where an interaction between Aβ and activated microglia sets the pace for tau spread across Braak stages.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

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