Heart fatty acid binding protein and Aβ-associated Alzheimer's neurodegeneration - PubMed (original) (raw)

Heart fatty acid binding protein and Aβ-associated Alzheimer's neurodegeneration

Rahul S Desikan et al. Mol Neurodegener. 2013.

Abstract

Background: Epidemiological and molecular findings suggest a relationship between Alzheimer's disease (AD) and dyslipidemia, although the nature of this association is not well understood.

Results: Using linear mixed effects models, we investigated the relationship between CSF levels of heart fatty acid binding protein (HFABP), a lipid binding protein involved with fatty acid metabolism and lipid transport, amyloid-β (Aβ), phospho-tau, and longitudinal MRI-based measures of brain atrophy among 295 non-demented and demented older individuals. Across all participants, we found a significant association of CSF HFABP with longitudinal atrophy of the entorhinal cortex and other AD-vulnerable neuroanatomic regions. However, we found that the relationship between CSF HABP and brain atrophy was significant only among those with low CSF Aβ1-42 and occurred irrespective of phospho-tau181p status.

Conclusions: Our findings indicate that Aβ-associated volume loss occurs in the presence of elevated HFABP irrespective of phospho-tau. This implicates a potentially important role for fatty acid binding proteins in Alzheimer's disease neurodegeneration.

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Figures

Figure 1

Figure 1

Three-dimensional representations of the neuroanatomic regions examined in the current study (only one hemisphere is shown). All of the examined neocortical regions are illustrated in the lateral and medial views of the gray matter surface (top row). The two non-neocortical regions (i.e., the hippocampus and amygdala) are illustrated in the coronal view of a T1-weighted MRI image (bottom row). Regions illustrated in red constitute the 'AD-vulnerable ROI’ (for further details please see manuscript text).

Figure 2

Figure 2

(A) Spaghetti plots illustrating atrophy of the entorhinal cortex among all participants classified as low Aβ 1–42 and high HFABP (based on median value of FABP) (top left panel), low Aβ 1–42 and low HFABP (top right panel), high Aβ 1–42 and high FABP (bottom left panel), and high Aβ 1–42 and low FABP (bottom right panel). The red line indicates the mean atrophy rate for the four respective groups (i.e. low Aβ1–42 and high FABP, low Aβ1–42 and low FABP, high Aβ1–42 and high FABP and high Aβ1–42 and low FABP). As illustrated, the slopes of the red lines are significantly different depending on CSF Aβ1–42 status (please see text for further details). (B) Spaghetti plots illustrating atrophy of the entorhinal cortex among all participants classified as high p-tau181p and high HFABP (based on median value of FABP) (top left panel), high p-tau181p and low HFABP (top right panel), low p-tau181p and high FABP (bottom left panel), and low p-tau181p and low FABP (bottom right panel). The red line indicates the mean atrophy rate for the four respective groups (i.e. high p-tau181p and high FABP, high p-tau181p and low FABP, low p-tau181p and high FABP and low p-tau181p and low FABP). As illustrated, the slopes of the red lines are not significantly different depending on CSF p-tau181p status (please see text for further details).

Figure 3

Figure 3

Scatter plots demonstrating the relationship between baseline CSF levels of HFABP (quality-controlled, transformed values as described in reference 18) CSF p-tau 181p (top left), CSF ApoC III (top right), CSF ApoD (bottom left) and CSF ApoE (bottom right). The black line represents the best-fit regression line.

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