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

Abstract

Objective: To test the hypothesis that beta-amyloid (Abeta) burden is associated with rates of brain atrophy.

Methods: 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.

Results: 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.

Interpretation: These findings suggest that rate of brain volume loss is not determined by the amount of insoluble Abeta in the gray matter.

Figure 1

Examples of the different visual grading of Aβ burden including mild Aβ burden (A), moderate Aβ burden (B), and severe Aβ burden (C).

Figure 2

Box plots of proportion area occupied by Aβ. The horizontal lines of the boxes represent the 25^th, 50^th (median), and 75^th percentiles of the distributions. The vertical lines extending from the boxes stop at the most extreme data point within 1.5 inter-quartile ranges of the box. Points beyond this are individually identified. Ave = average across frontal (Fr) and occipital (Occip) regions.

Figure 3

Relationship between BSI volumes and numeric Braak stage or age. The open circles indicate demented subjects while the triangles indicate non-demented subjects. The partial correlation for the whole group from table 2 has been added for reference.