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. 2015 Aug;36(8):2340-7.
doi: 10.1016/j.neurobiolaging.2015.04.011. Epub 2015 Apr 25.

Cerebrospinal fluid biomarkers and cerebral atrophy in distinct clinical variants of probable Alzheimer's disease

Rik Ossenkoppele  1 , Niklas Mattsson  2 , Charlotte E Teunissen  3 , Frederik Barkhof  4 , Yolande Pijnenburg  5 , Philip Scheltens  5 , Wiesje M van der Flier  6 , Gil D Rabinovici  7
Affiliations

Cerebrospinal fluid biomarkers and cerebral atrophy in distinct clinical variants of probable Alzheimer's disease

Rik Ossenkoppele et al. Neurobiol Aging. 2015 Aug.

Abstract

Different clinical variants of probable Alzheimer's disease (AD) share underlying plaques and tangles but show distinct atrophy patterns. We included 52 posterior cortical atrophy, 29 logopenic variant primary progressive aphasia, 53 early-onset and 42 late-onset AD patients, selected for abnormal cerebrospinal fluid (CSF)-amyloid-beta42, with CSF and magnetic resonance imaging data available. Bootstrapping revealed no differences in the prevalence of abnormal CSF total-tau and phosphorylated-tau between probable AD variants (range total-tau: 84.9%-92.3%, phosphorylated-tau: 79.2%-93.1%, p > 0.05). Voxelwise linear regressions showed various relationships between lower CSF-Aβ42 and syndrome-specific atrophy, involving precuneus, posterior cingulate, and medial temporal lobe in early-onset AD, occipital cortex and middle temporal gyrus in posterior cortical atrophy; anterior cingulate, insular cortex and precentral gyrus (left > right) in logopenic variant primary progressive aphasia; and medial temporal lobe, thalamus, and temporal pole in late-onset AD (all at p < 0.001 uncorrected). In contrast, CSF-tau was not related to gray matter atrophy in any group. Our findings suggest that lower CSF-amyloid-beta42 - and not increased total-tau and phosphorylated-tau - relates to reduced gray matter volumes, mostly in regions that are typically atrophied in distinct clinical variants of probable AD.

Keywords: Alzheimer's disease; Amyloid; Atrophy; Cerebrospinal fluid; Magnetic resonance imaging; Tau.

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Figures

FIGURE 1
FIGURE 1
Boxplots for CSF total tau (A) and phosphorylated tau (B) levels (ng/L) for each AD variant. ANOVA with post-hoc Bonferroni tests revealed no differences between groups.
FIGURE 2
FIGURE 2
Voxelwise linear regression analyses between CSF Aβ42 and gray matter volume on MRI in early-onset AD (A), posterior cortical atrophy (B), logopenic variant primary progressive aphasia (C) and late-onset AD (D). T-maps are superimposed on a brain template implemented in Caret software, ranging from 2 to 5 for visualization purposes (T values of 3.27 for EOAD, 3.28 for PCA, 3.48 for lvPPA and 3.33 for LOAD correspond to the p<0.001 threshold; In the text only the significant regions have been reported).
FIGURE 3
FIGURE 3
Scatterplots for each probable AD variant of CSF Aβ42 and gray matter probability in the cluster with the greatest T-value: Posterior cingulate cortex for EOAD (A), lateral occipital cortex for PCA (B), precentral gyrus for lvPPA (C), and medial temporal lobe for LOAD (D).
See this image and copyright information in PMC

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References

    1. Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers dement. 2011;7:270–279. - PMC - PubMed
    1. Ashburner J. A fast diffeomorphic image registration algorithm. NeuroImage. 2007;38:95–113. - PubMed
    1. Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, Marcus DS, Cairns NJ, Xie X, Blazey TM, Holtzman DM, Santacruz A, Buckles V, Oliver A, Moulder K, Aisen PS, Ghetti B, Klunk WE, McDade E, Martins RN, Masters CL, Mayeux R, Ringman JM, Rossor MN, Schofield PR, Sperling RA, Salloway S, Morris JC Dominantly Inherited Alzheimer, N. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. New Engl J Med. 2012;367:795–804. - PMC - PubMed
    1. Baumann TP, Duyar H, Sollberger M, Kuhle J, Regeniter A, Gomez-Mancilla B, Schmidtke K, Monsch AU. CSF-tau and CSF-Abeta (1–42) in posterior cortical atrophy. Dement geriatr cog dis. 2010;29:530–533. - PubMed
    1. Benson DF, Davis RJ, Snyder BD. Posterior cortical atrophy. Arch neurol. 1988;45:789–793. - PubMed

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