Brain atrophy in healthy aging is related to CSF levels of Aβ1-42

Abstract

Reduced levels of beta-amyloid(1-42) (Abeta1-42) and increased levels of tau proteins in the cerebrospinal fluid (CSF) are found in Alzheimer's disease (AD), likely reflecting Abeta deposition in plaques and neuronal and axonal damage. It is not known whether these biomarkers are associated with brain atrophy also in healthy aging. We tested the relationship between CSF levels of Abeta1-42 and tau (total tau and tau phosphorylated at threonine 181) proteins and 1-year brain atrophy in 71 cognitively normal elderly individuals. Results showed that under a certain threshold value, levels of Abeta1-42 correlated highly with 1-year change in a wide range of brain areas. The strongest relationships were not found in the regions most vulnerable early in AD. Above the threshold level, Abeta1-42 was not related to brain changes, but significant volume reductions as well as ventricular expansion were still seen. It is concluded that Abeta1-42 correlates with brain atrophy and ventricular expansion in a subgroup of cognitively normal elderly individuals but that reductions independent of CSF levels of Abeta1-42 is common. Further research and follow-up examinations over several years are needed to test whether degenerative pathology will eventually develop in the group of cognitively normal elderly individuals with low levels of Abeta1-42.

Figure 1.

Nonlinear relationships between Aβ1-42 and volume reductions for cortical ROIs. A nonparametric local smoothing technique (the smoothing spline) was used to depict nonlinear relationships (red lines) for the 71 participants. A relationship between Aβ1-42 and percentage change was found only when the concentration of Aβ1-42 in the CSF was below ≈ 175 pg/mL.

Figure 2.

Nonlinear relationships between Aβ1-42 and volumetric reductions of subcortical ROIs and ventricular expansion. A nonparametric local smoothing technique (the smoothing spline) was used to depict nonlinear relationships (red lines) for the 71 participants.

Figure 3.

Cortical reductions in the high- and the low-Aβ1-42 groups. Based on the break point of the smoothing spline graphs (see Figs 1 and 2), a high-Aβ1-42 group and a low-Aβ1-42 group were defined. Atrophy was calculated as percentage change in cortex point by point across the brain surface. The reductions are generally larger in the low- than in the high-Aβ1-42 group.

Figure 4.

Correlations between Aβ1-42 and annual cortical change. Correlations between cortical change point by point across the brain surface and Aβ1-42 were calculated, color coded, and displayed as an overlay on the template brain. This was done for the high- and the low-Aβ1-42 groups separately. The lower P value threshold is equal to a false discovery rate of <0.05 (corrected for multiple comparisons).