Relationship between plasma analytes and SPARE-AD defined brain atrophy patterns in ADNI

Abstract

Different inflammatory and metabolic pathways have been associated with Alzheimeŕs disease (AD). However, only recently multi-analyte panels to study a large number of molecules in well characterized cohorts have been made available. These panels could help identify molecules that point to the affected pathways. We studied the relationship between a panel of plasma biomarkers (Human DiscoveryMAP) and presence of AD-like brain atrophy patterns defined by a previously published index (SPARE-AD) at baseline in subjects of the ADNI cohort. 818 subjects had MRI-derived SPARE-AD scores, of these subjects 69% had plasma biomarkers and 51% had CSF tau and Aβ measurements. Significant analyte-SPARE-AD and analytes correlations were studied in adjusted models. Plasma cortisol and chromogranin A showed a significant association that did not remain significant in the CSF signature adjusted model. Plasma macrophage inhibitory protein-1α and insulin-like growth factor binding protein 2 showed a significant association with brain atrophy in the adjusted model. Cortisol levels showed an inverse association with tests measuring processing speed. Our results indicate that stress and insulin responses and cytokines associated with recruitment of inflammatory cells in MCI-AD are associated with its characteristic AD-like brain atrophy pattern and correlate with clinical changes or CSF biomarkers.

Figure 1. SPARE AD values in the different groups according to clinical diagnosis (CN, MCI, AD) and CSF signature (N-CSF: non AD-like CSF signature; P-CSF: pathological AD CSF signature).

Figure 2. Scatterplot showing log-transformed total-tau/Aβ₄₂ ratio and power-transformed SPARE-AD (A) and power transformed SPARE-AD and ADAS-Cog score (B).

The marginal box plots on x-axis represent the distribution of the power transformed SPARE-AD and the marginal box-plots on the y-axis represent the t-tau/Aβ₄₂ ratio (A) and ADAS-Cog (B) values.

Figure 3. Regression of cortisol without adjustment (A), with adjustment for age (B) and with adjustment for age and clinical diagnosis (C), against regional grey matter (GM) volumes.

The color scale represents in blue a decrease in GM volumes associated to a increase levels of the biomarker in plasma. White matter changes (in red) indicate abnormal brain tissue, commonly associated with leukoaraiosis.

Figure 4. Regression of MIP-1α without (A), with adjustment for age (B) and with adjustment for age and clinical diagnosis (C), against grey matter (GM) volumes.

The color scale represents in blue a decrease in GM volumes associated to increased levels of the biomarker in plasma. White matter changes (in red) indicate abnormal periventricular brain tissue, commonly associated with leukoaraiosis.