Journal
NEUROBIOLOGY OF AGING
Volume 70, Issue -, Pages 160-169Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2018.06.016
Keywords
Alzheimer's disease; Functional MRI; Hyperexcitability; Hippocampus; Tau; Amyloid beta peptide
Categories
Funding
- Intramural Research Programs of the National Institute on Aging (NIA)
- National Institute on Drug Abuse (NIDA)
- Intramural Research Programs of the National Institute on Aging
- National Institute on Drug Abuse
Ask authors/readers for more resources
Alzheimer's disease (AD) is characterized by progressive cognitive impairment and by extensive neuronal loss associated with extracellular amyloid beta-peptide (A beta) plaques and intraneuronal tau pathology in temporal and parietal lobes. AD patients are at increased risk for epileptic seizures, and data from experimental models of AD suggest that aberrant neuronal network activity occurs early in the disease process before cognitive deficits and neuronal degeneration. The contributions of A beta and/or tau pathologies to dysregulation of neuronal network activity are unclear. Using a transgenic mouse model of AD (3 x TgAD mice) in which there occurs differential age-dependent development of tau and Ab plaque pathologies, we applied analysis of resting state functional magnetic resonance imaging regional homogeneity, a measure of local synchronous activity, to discriminate the effects of Ab and tau on neuronal network activity throughout the brain. Compared to age-matched wild-type mice, 6- to 8-month-old 3 x TgAD mice exhibited increased regional homogeneity in the hippocampus and parietal and temporal cortices, regions with tau pathology but not A beta pathology at this age. By 18-24 months of age, 3 x TgAD mice exhibited extensive tau and A beta pathologies involving the hippocampus and multiple functionally related brain regions, with a spatial expansion of increased local synchronous activity to include those regions. Our findings demonstrate that age-related brain regional hypersynchronous activity is associated with early tau pathology in a mouse model, consistent with a role for early tau pathology in the neuronal circuit hyperexcitability that is believed to precede and contribute to neuronal degeneration in AD. Published by Elsevier Inc.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available