Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2018 Apr 24;115(17):4483-4488.
doi: 10.1073/pnas.1721694115. Epub 2018 Apr 9.

β-Amyloid Accumulation in the Human Brain After One Night of Sleep Deprivation

Affiliations
Free PMC article
Clinical Trial

β-Amyloid Accumulation in the Human Brain After One Night of Sleep Deprivation

Ehsan Shokri-Kojori et al. Proc Natl Acad Sci U S A. .
Free PMC article

Abstract

The effects of acute sleep deprivation on β-amyloid (Aβ) clearance in the human brain have not been documented. Here we used PET and 18F-florbetaben to measure brain Aβ burden (ABB) in 20 healthy controls tested after a night of rested sleep (baseline) and after a night of sleep deprivation. We show that one night of sleep deprivation, relative to baseline, resulted in a significant increase in Aβ burden in the right hippocampus and thalamus. These increases were associated with mood worsening following sleep deprivation, but were not related to the genetic risk (APOE genotype) for Alzheimer's disease. Additionally, baseline ABB in a range of subcortical regions and the precuneus was inversely associated with reported night sleep hours. APOE genotyping was also linked to subcortical ABB, suggesting that different Alzheimer's disease risk factors might independently affect ABB in nearby brain regions. In summary, our findings show adverse effects of one-night sleep deprivation on brain ABB and expand on prior findings of higher Aβ accumulation with chronic less sleep.

Keywords: Alzheimer’s disease; beta amyloid; glymphatic system; hippocampus; sleep.

Conflict of interest statement

Conflict of interest statement: S.D.S. was an employee of Piramal Pharma Inc., which partly supported the radiotracer for this study.

Figures

Fig. 1.
Fig. 1.
Effects of one-night SD on ABB. (A) Voxelwise paired t test between RW and SD conditions highlighting the hippocampus as well as other subcortical structures (PFWE < 0.05, cluster-size corrected) (Table S1). (B) Subject-level changes in FBB SUVr (in the red cluster identified in A) from RW to SD. There was no significant effect of gender, or gender × sleep interaction (P > 0.15). (C) Association between changes in mood from RW to SD and changes in the FBB SUVr for the cluster identified in A. Mood change was quantified using the principal component of the changes in self-report measures from RW to SD, which accounted for 35.5% of the variance. Self-report measures of alert, friendly, happy, social, and energetic significantly decreased, and measures of tired and difficulty staying awake significantly increased from RW to SD (P < 0.001, two-tailed) (see also Fig. S1). (D) Average FBB SUVr in a priori hippocampus ROIs across subjects. Error bars show standard deviation (Methods).
Fig. 2.
Fig. 2.
Relationship between SH, APOE genotype, and ABB. (A) Regression of FBB SUVr (indexing ABB) for the red cluster shown in Fig. 1A at RW against SH. (B) Three-dimensional rendering of the areas showing an association between higher FBB SUVr at RW and lower SH (red clusters, PFWE < 0.05, cluster-size corrected) (Table S3), as well as areas showing an association between higher FBB SUVr and higher APOE-based genetic risk for AD (quantified as log of ORAD) (green clusters, PFWE < 0.05, cluster-size corrected, except the right-sided subcortical cluster, which was cluster size-corrected at qFDR < 0.05) (Table S4). The subcortical clusters related to SH and ORAD had minimal spatial overlap (18 voxels, <3%) (Tables S3 and S4). Notably, FBB SUVr within the SH-related subcortical clusters (red, B) was not associated with ORAD (P = 0.25) and FBB SUVr within the ORAD-related subcortical clusters (green, B) was not associated with SH (P = 0.2).

Similar articles

See all similar articles

Cited by 55 articles

See all "Cited by" articles

References

    1. Nedergaard M. Neuroscience. Garbage truck of the brain. Science. 2013;340:1529–1530. - PMC - PubMed
    1. Mestre H, Kostrikov S, Mehta RI, Nedergaard M. Perivascular spaces, glymphatic dysfunction, and small vessel disease. Clin Sci (Lond) 2017;131:2257–2274. - PMC - PubMed
    1. Xie L, et al. Sleep drives metabolite clearance from the adult brain. Science. 2013;342:373–377. - PMC - PubMed
    1. Kang J-E, et al. Amyloid-β dynamics are regulated by orexin and the sleep-wake cycle. Science. 2009;326:1005–1007. - PMC - PubMed
    1. Tabuchi M, et al. Sleep interacts with aβ to modulate intrinsic neuronal excitability. Curr Biol. 2015;25:702–712. - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources

Feedback