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Reduced repetition suppression in aging is driven by tau-related hyperactivity in medial temporal lobe

Adams, Jenna N. (author)
University of California, Berkeley
Maass, Anne (author)
German Center for Neurodegenerative Diseases (DZNE), Bonn,University of California, Berkeley
Berron, David (author)
Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,German Center for Neurodegenerative Diseases (DZNE), Bonn
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Harrison, Theresa M. (author)
University of California, Berkeley
Baker, Suzanne L. (author)
Lawrence Berkeley National Laboratory
Thomas, Wesley P. (author)
Lawrence Berkeley National Laboratory
Stanfill, Morgan (author)
University of California, Berkeley
Jagust, William J. (author)
University of California, Berkeley,Lawrence Berkeley National Laboratory
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 (creator_code:org_t)
2021
2021
English 15 s.
In: The Journal of Neuroscience. - 0270-6474. ; 41:17, s. 3917-3931
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Tau deposition begins in the medial temporal lobe (MTL) in aging and Alzheimer's disease (AD), and MTL neural dysfunction is commonly observed in these groups. However, the association between tau and MTL neural activity has not been fully characterized. We investigated the effects of tau on repetition suppression, the reduction of activity for repeated stimulus presentations compared to novel stimuli. We used task-based functional MRI (fMRI) to assess MTL subregional activity in 21 young adults (YA) and 45 cognitively normal human older adults (OA; total sample: 37 females, 29 males). AD pathology was measured with position emission tomography (PET), using 18F-Flortaucipir for tau and 11C-Pittsburgh compound B (PiB) for amyloid-b (Ab). The MTL was segmented into six subregions using high-resolution structural images. We compared the effects of low tau pathology, restricted to entorhinal cortex and hippocampus (Tau- OA), to high tau pathology, also occurring in temporal and limbic regions (Tau1 OA). Low levels of tau (Tau- OA vs YA) were associated with reduced repetition suppression activity specifically in anterolateral entorhinal cortex (alEC) and hippocampus, the first regions to accumulate tau. High tau pathology (Tau1 vs Tau- OA) was associated with widespread reductions in repetition suppression across MTL. Further analyses indicated that reduced repetition suppression was driven by hyperactivity to repeated stimuli, rather than decreased activity to novel stimuli. Increased activation was associated with entorhinal tau, but not Ab. These findings reveal a link between tau deposition and neural dysfunction in MTL, in which tau-related hyperactivity prevents deactivation to repeated stimuli, leading to reduced repetition suppression.

Subject headings

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

Keyword

Aging
Alzheimer's disease
FMRI
PET
Repetition suppression
Tau

Publication and Content Type

art (subject category)
ref (subject category)

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