Amyloid plaques disrupt resting state default mode network connectivity in cognitively normal elderly.
BACKGROUND
Important functional connections within the default mode network (DMN) are disrupted in Alzheimer's disease (AD), likely from amyloid-beta (Abeta) plaque-associated neuronal toxicity. Here, we sought to determine if pathological effects of Abeta amyloid plaques could be seen, even in the absence of a task, by examining functional connectivity in cognitively normal participants with and without preclinical amyloid deposition.


METHODS
Participants with Alzheimer's disease (AD) (n = 35) were compared with 68 cognitively normal participants who were further subdivided by positron emission tomography (PET) Pittsburgh Compound-B (PIB) imaging into those without evidence of brain amyloid (PIB-) and those with brain amyloid (PIB+) deposition.


RESULTS
Resting state functional magnetic resonance imaging (fMRI) demonstrated that, compared with the PIB- group, the PIB+ group differed significantly in functional connectivity of the precuneus to hippocampus, parahippocampus, anterior cingulate, dorsal cingulate, gyrus rectus, superior precuneus, and visual cortex. These differences were in the same regions and in the same direction as differences found in the AD group.


CONCLUSIONS
Thus, before any manifestations of cognitive or behavioral changes, there were differences in resting state connectivity in cognitively normal subjects with brain amyloid deposition, suggesting that early manifestation of Abeta toxicity can be detected using resting state fMRI.
Sheline
Yvette I
YI
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA. yvette@npg.wustl.edu
Raichle
Marcus E
ME
Snyder
Abraham Z
AZ
Morris
John C
JC
Head
Denise
D
Wang
Suzhi
S
Mintun
Mark A
MA
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology*; D001931:Brain Mapping / Q000379:methods; D005260:Female; D015577:Geriatric Assessment; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009415:Nerve Net / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology; D010100:Oxygen / Q000097:blood; D049268:Positron-Emission Tomography / Q000379:methods; D011569:Psychiatric Status Rating Scales; D012146:Rest / Q000502:physiology*; D013223:Statistics as Topic; D013844:Thiazoles
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D013844:Thiazoles; D010100:Oxygen