title: Altered functional connectivity in asymptomatic MAPT subjects: a comparison to bvFTD.
abstract: OBJECTIVE
  To determine whether functional connectivity is altered in subjects with mutations in the microtubule associated protein tau (MAPT) gene who were asymptomatic but were destined to develop dementia, and to compare these findings to those in subjects with behavioral variant frontotemporal dementia (bvFTD).
  
  
  METHODS
  In this case-control study, we identified 8 asymptomatic subjects with mutations in MAPT and 8 controls who screened negative for mutations in MAPT. Twenty-one subjects with a clinical diagnosis of bvFTD were also identified and matched to 21 controls. All subjects had resting-state fMRI. In-phase functional connectivity was assessed between a precuneus seed in the default mode network (DMN) and a fronto-insular cortex seed in the salience network, and the rest of the brain. Atlas-based parcellation was used to assess functional connectivity and gray matter volume across specific regions of interest.
  
  
  RESULTS
  The asymptomatic MAPT subjects and subjects with bvFTD showed altered functional connectivity in the DMN, with reduced in-phase connectivity in lateral temporal lobes and medial prefrontal cortex, compared to controls. Increased in-phase connectivity was also observed in both groups in the medial parietal lobe. Only the bvFTD group showed altered functional connectivity in the salience network, with reduced connectivity in the fronto-insular cortex and anterior cingulate. Gray matter loss was observed across temporal, frontal, and parietal regions in bvFTD, but not in the asymptomatic MAPT subjects.
  
  
  CONCLUSIONS
  Functional connectivity in the DMN is altered in MAPT subjects before the occurrence of both atrophy and clinical symptoms, suggesting that changes in functional connectivity are early features of the disease.
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA. Whitwell.jennifer@mayo.edu
authors.forename: J L
authors.initials: JL
authors.lastname: Whitwell
authors.forename: K A
authors.initials: KA
authors.lastname: Josephs
authors.forename: R
authors.initials: R
authors.lastname: Avula
authors.forename: N
authors.initials: N
authors.lastname: Tosakulwong
authors.forename: S D
authors.initials: SD
authors.lastname: Weigand
authors.forename: M L
authors.initials: ML
authors.lastname: Senjem
authors.forename: P
authors.initials: P
authors.lastname: Vemuri
authors.forename: D T
authors.initials: DT
authors.lastname: Jones
authors.forename: J L
authors.initials: JL
authors.lastname: Gunter
authors.forename: M
authors.initials: M
authors.lastname: Baker
authors.forename: Z K
authors.initials: ZK
authors.lastname: Wszolek
authors.forename: D S
authors.initials: DS
authors.lastname: Knopman
authors.forename: R
authors.initials: R
authors.lastname: Rademakers
authors.forename: R C
authors.initials: RC
authors.lastname: Petersen
authors.forename: B F
authors.initials: BF
authors.lastname: Boeve
authors.forename: C R
authors.initials: CR
authors.lastname: Jack
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000502:physiology* / Q000503:physiopathology; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009415:Nerve Net / Q000502:physiology* / Q000503:physiopathology; D012919:Social Behavior; D055815:Young Adult; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins