Movatterモバイル変換

[0]ホーム
URL:

Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

Silverchair Information Systems full text link Silverchair Information Systems Free PMC article
Full text links

Actions

.2015 Sep;25(9):2556-65.
doi: 10.1093/cercor/bhu055. Epub 2014 Mar 21.

The Roots of Alzheimer's Disease: Are High-Expanding Cortical Areas Preferentially Targeted?†

Affiliations

The Roots of Alzheimer's Disease: Are High-Expanding Cortical Areas Preferentially Targeted?†

Anders M Fjell et al. Cereb Cortex.2015 Sep.

Abstract

Alzheimer's disease (AD) is regarded a human-specific condition, and it has been suggested that brain regions highly expanded in humans compared with other primates are selectively targeted. We calculated shared and unique variance in the distribution of AD atrophy accounted for by cortical expansion between macaque and human, affiliation to the default mode network (DMN), ontogenetic development and normal aging. Cortical expansion was moderately related to atrophy, but a critical discrepancy was seen in the medial temporo-parietal episodic memory network. Identification of "hotspots" and "coldspots" of expansion across several primate species did not yield compelling evidence for the hypothesis that highly expanded regions are specifically targeted. Controlling for distribution of atrophy in aging substantially attenuated the expansion-AD relationship. A path model showed that all variables explained unique variance in AD atrophy but were generally mediated through aging. This supports a systems-vulnerability model, where critical networks are subject to various negative impacts, aging in particular, rather than being selectively targeted in AD. An alternative approach is suggested, focused on the interplay of the phylogenetically old and preserved medial temporal lobe areas with more highly expanded association cortices governed by different principles of plasticity and stability.

Keywords: Alzheimer's disease; aging; cerebral cortex; default mode network; evolution.

© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Regional distribution of atrophy and cortical expansion. (A) Meanannual atrophy in terms of volume reduction in AD,z-transformed toremove scaling effects. (B)z-transformed corticalexpansion between macaque and human. (C)z-transformed maps of atrophy in terms of volume reductions innormal aging. For all panels, red–yellow indicates higher than mean annualatrophy/cortical expansion, whereas blue–cyan indicates lower than meanatrophy/cortical expansion. Scales go from 2 (red–yellow) to −2 (blue–cyan). Thebrains are semi-inflated to allow better visualization of effects within sulci.
Figure 2.
Figure 2.
AD atrophy, cortical expansion and DMN. (A) Mean AD atrophy andexpansion (z-scores) were quantified within 34 cortical regions ofinterest to illustrate variability across regions. Thex-axisdenotes degree of cortical expansion from relatively lower (blue–cyan axis color) tohigher (red–yellow axis color). The transition point between blue and red axis colordenotes mean expansion across the surface. They-axis denotespercentage annual cortical volume decline in the AD patients. The color of the dotsindicates from which gross region of the brain they are taken. Although there is acorrelation between how much cortical expansion is seen within a region and theamount of AD atrophy, there are also regions not following this tendency, forexample, the medial temporal regions characterized by relatively low degree ofexpansion but high levels of atrophy in AD. (B) Thez-transformed cortical expansion and AD atrophy maps from Fig. 1 were thresholded at 0.5 <Z < −0.5. Areas of correlation were characterized byZ > 0.5 (green) orZ < −0.5 (yellow) forboth cortical expansion and AD, whereas areas of anti-correlation (pink) werecharacterized by combinations ofZ > 0.5 withZ< −0.5. The medial surface is slightly tilted to allow inspection of inferiortemporal and fusiform cortex. (C) A similar procedure was used toshow areas of high atrophy within DMN (green), low atrophy outside DMN (yellow), andhigh atrophy outside DMN (pink).
Figure 3.
Figure 3.
A conserved pattern of differential expansion across primate species. Corticalexpansion (z-scores) from comparisons between cortical area ofsmaller versus larger brained Simian primates. From left to right are shown marmosetversus capuchin, marmoset versus macaque, and macaque versus humans, as well as themean expansion across all species. General patterns of high and relatively lowexpansion are well preserved across species. The medial temporal cortex (lowerpanel) showed high degree of preservation across all comparisons (thresholded byz < −1).
Figure 4.
Figure 4.
Hotspots and coldspots of cortical expansion. Upper panel: the average expansionmaps across marmoset, capuchin, macaque, and human were thresholded atz > 1 orz < −1 to reveal regions ofconsistently high (“hotspots”—green-yellow) and consistently low(“coldspots”—blue-pink) cortical expansion through across primates. Lower panel:mean atrophy in AD was quantified within the 2 hotspot regions (H1 and H2) and the 2coldspot regions (C1 and C2). H1 and C1 showed elevated rate of atrophy, whereas C2showed reduced decline.
Figure 5.
Figure 5.
Default mode network (DMN) and cortical expansion. Upper panel: delineation of theDMN based on Yeo et al. (2011). Colorsdenote the probability for each vertex being a part of the DMN. The scale goes from0.15 (red) to 1 (yellow). Lower panel: atrophy and expansion from the maps in Fig. 1 were extracted for vertices insideversus outside DMN and plotted in terms ofz-scores. Atrophy andexpansion are larger for DMN vertices than vertices outside DMN. All contrasts weresignificant (P < 0.05, corrected).
Figure 6.
Figure 6.
Path model of shared and unique contributions to distribution of AD pathology. Apath diagram was constructed to show how the variance was distributed amongvariables. Arrows show relationships between any 2 variables in terms of independent(start of line) versus dependent (end of arrow); colors and thickness of linescorrespond to standardized partial path weights.
See this image and copyright information in PMC

References

    1. Addis DR, Pan L, Vu MA, Laiser N, Schacter DL. 2009. Constructive episodic simulation of the future and the past: distinct subsystems of a core brain network mediate imagining and remembering. Neuropsychologia. 47:2222–2238. - PubMed
    1. Aimone JB, Deng W, Gage FH. 2010. Adult neurogenesis: integrating theories and separating functions. Trends Cogn Sci. 14:325–337. - PMC - PubMed
    1. Andreasen NC, O'Leary DS, Cizadlo T, Arndt S, Rezai K, Watkins GL, Ponto LL, Hichwa RD. 1995. Remembering the past: two facets of episodic memory explored with positron emission tomography. Am J Psychiatry. 152:1576–1585. - PubMed
    1. Andrews-Hanna JR, Reidler JS, Sepulcre J, Poulin R, Buckner RL. 2010. Functional-anatomic fractionation of the brain's default network. Neuron. 65:550–562. - PMC - PubMed
    1. Bardet J, Essen DK, Feron C, Gouat P. 2007. Evaluation of the social bond: a new method tested inMus spicilegus. Comptes Rendus Biol. 330:837–843. - PubMed

MeSH terms

Grants and funding

LinkOut - more resources

Full text links
Silverchair Information Systems full text link Silverchair Information Systems Free PMC article
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

[8]ページ先頭
©2009-2026 Movatter.jp