title: Amyloid accelerates tau propagation and toxicity in a model of early Alzheimer's disease.
abstract: BACKGROUND
  In early stages of Alzheimer's disease (AD), neurofibrillary tangles (NFT) are largely restricted to the entorhinal cortex and medial temporal lobe. At later stages, when clinical symptoms generally occur, NFT involve widespread limbic and association cortices. At this point in the disease, amyloid plaques are also abundantly distributed in the cortex. This observation from human neuropathological studies led us to pose two alternative hypotheses: that amyloid in the cortex is permissive for the spread of tangles from the medial temporal lobe, or that these are co-occurring but not causally related events simply reflecting progression of AD pathology.
  
  
  RESULTS
  We now directly test the hypothesis that cortical amyloid acts as an accelerant for spreading of tangles beyond the medial temporal lobe. We crossed rTgTauEC transgenic mice that demonstrate spread of tau from entorhinal cortex to other brain structures at advanced age with APP/PS1 mice, and examined mice with either NFTs, amyloid pathology, or both. We show that concurrent amyloid deposition in the cortex 1) leads to a dramatic increase in the speed of tau propagation and an extraordinary increase in the spread of tau to distal brain regions, and 2) significantly increases tau-induced neuronal loss.
  
  
  CONCLUSIONS
  These data strongly support the hypothesis that cortical amyloid accelerates the spread of tangles throughout the cortex and amplifies tangle-associated neural system failure in AD.
authors: Amy M
authors: AM
authors: Pooler
authors: Manuela
authors: M
authors: Polydoro
authors: Eduardo A
authors: EA
authors: Maury
authors: Samantha B
authors: SB
authors: Nicholls
authors: Snigdha M
authors: SM
authors: Reddy
authors: Susanne
authors: S
authors: Wegmann
authors: Christopher
authors: C
authors: William
authors: Lubna
authors: L
authors: Saqran
authors: Ozge
authors: O
authors: Cagsal-Getkin
authors: Rose
authors: R
authors: Pitstick
authors: David R
authors: DR
authors: Beier
authors: George A
authors: GA
authors: Carlson
authors: Tara L
authors: TL
authors: Spires-Jones
authors: Bradley T
authors: BT
authors: Hyman
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D013702:Temporal Lobe / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D000682:Amyloid; D016875:tau Proteins