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

NEUROBIOLOGY OF AGING

卷:36

Article

Ossenkoppele, Rik^1,2,3,4,5  Mattsson, Niklas^6,7  Teunissen, Charlotte E.⁸  Barkhof, Frederik⁵  Pijnenburg, Yolande^3,4  Scheltens, Philip^3,4  van der Flier, Wiesje M.^3,4,9  Rabinovici, Gil D.^1,2 

[1] Univ Calif San Francisco, Memory & Aging Ctr, Dept Neurol, San Francisco, CA 94158 USA

[2] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA

[3] Vrije Univ Amsterdam Med Ctr, Dept Neurol, Amsterdam, Netherlands

[4] Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands

[5] Vrije Univ Amsterdam Med Ctr, Dept Radiol & Nucl Med, Amsterdam, Netherlands

[6] Dept Vet Affairs Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA

[7] Univ Gothenburg, Inst Neurosci & Physiol, Lab Clin Neurochem, Gothenburg, Sweden

[8] Vrije Univ Amsterdam Med Ctr, Dept Clin Chem, Amsterdam, Netherlands

[9] Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands

关键词: Alzheimer's disease;    Cerebrospinal fluid;    Magnetic resonance imaging;    Amyloid;    Tau;    Atrophy;   

DOI  :  10.1016/j.neurobiolaging.2015.04.011

来源: Elsevier

【 摘 要 】

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) eamyloid-beta(42), 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-A beta(42) 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 eamyloid-beta(42) - 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. (C) 2015 Elsevier Inc. All rights reserved.

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