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Beta-amyloid burden is not associated with rates of brain atrophy.

ABSTRACT: To test the hypothesis that beta-amyloid (Abeta) burden is associated with rates of brain atrophy.Forty-five subjects who had been prospectively studied, died, and had an autopsy diagnosis of low, intermediate, or high probability of Alzheimer's disease who had two volumetric head magnetic resonance imaging scans were identified. Compact and total (compact + diffuse) Abeta burden was measured using a computerized image analyzer with software program to detect the proportion of gray matter occupied by Abeta. Visual ratings of Abeta burden were also performed. The boundary shift integral was used to calculate change over time in whole-brain and ventricular volume. All boundary shift integral results were annualized by adjusting for scan interval. Demographics, cognitive measures, clinical diagnoses, apolipoprotein E genotype, neurofibrillary tangle (NFT) pathology, and vascular lesion burden were determined.There was no correlation between compact or total Abeta burden, or visual Abeta ratings, and rates of brain loss or ventricular expansion in all subjects. However, significant correlations were observed between rates of brain loss and age, Braak NFT stage, and change over time in cognitive measures. These features also correlated with rates of ventricular expansion. The rates of brain loss and ventricular expansion were greater in demented compared with nondemented subjects.These findings suggest that rate of brain volume loss is not determined by the amount of insoluble Abeta in the gray matter.

SUBMITTER: Josephs KA

PROVIDER: S-EPMC2735194 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

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Beta-amyloid burden is not associated with rates of brain atrophy.

Josephs Keith A KA Whitwell Jennifer L JL Ahmed Zeshan Z Shiung Maria M MM Weigand Stephen D SD Knopman David S DS Boeve Bradley F BF Parisi Joseph E JE Petersen Ronald C RC Dickson Dennis W DW Jack Clifford R CR

Annals of neurology 20080201 2

<h4>Objective</h4>To test the hypothesis that beta-amyloid (Abeta) burden is associated with rates of brain atrophy.<h4>Methods</h4>Forty-five subjects who had been prospectively studied, died, and had an autopsy diagnosis of low, intermediate, or high probability of Alzheimer's disease who had two volumetric head magnetic resonance imaging scans were identified. Compact and total (compact + diffuse) Abeta burden was measured using a computerized image analyzer with software program to detect th ...[more]

PMID: 17894374

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Project description:IntroductionAlzheimer's disease (AD) is characterized by the accumulation of β-amyloid (Aβ) associated with brain atrophy and cognitive decline. The functional form to model the association between Aβ and regional brain atrophy has not been well defined. To determine the relationship between Aβ and atrophy, we compared the performance of the usual dichotomization of cerebrospinal fluid (CSF) Aβ to identify subjects as Aβ+ and Aβ- with a trilinear spline model of CSF Aβ.MethodsOne hundred and eighty-three subjects with mild cognitive impairment and 108 cognitively normal controls with baseline CSF Aβ and up to 4 years of longitudinal magnetic resonance imaging data from the Alzheimer's Disease Neuroimaging Initiative were analyzed using mixed-effects regression. Piecewise-linear splines were used to evaluate the nonlinear nature of the association between CSF Aβ and regional atrophy and to identify points of acceleration of atrophy with respect to Aβ. Several parameterizations of CSF Aβ were compared using likelihood ratio tests and the Akaike information criterion. Periods of acceleration of atrophy in which subjects transition from CSF Aβ negativity to CSF Aβ positivity were estimated from the spline models and tested for significance.ResultsSpline models resulted in better fits for many temporal and parietal regions compared with the dichotomous models. The trilinear model showed that periods of acceleration of atrophy varied greatly by region with early changes seen in the insula, amygdala, precuneus, hippocampus, and other temporal regions, occurring before the clinical threshold for CSF Aβ positivity.DiscussionThe use of piecewise-linear splines provides an improved model of the nonlinear association between CSF Aβ and regional atrophy in regions implicated in the progression of AD. The important biological finding of this work is that some brain regions show periods of accelerated volume loss well before the CSF Aβ42 threshold. This implies that signs of brain atrophy develop before the current conventional definition of "preclinical AD".

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Beta-amyloid burden is not associated with rates of brain atrophy.

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Beta-amyloid burden is not associated with rates of brain atrophy.

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