Cholesterol and LDL Relate to Neuritic Plaques and to APOE4 Presence but Not to Neurofibrillary Tangles

Elevated serum total cholesterol (TC) has been considered a risk factor for Alzheimer's disease (AD), but conflicting results have confused understanding of the relationships of serum lipids to the presence of AD in the elderly. Methods: To clarify these issues, we evaluated correlations of admission TC, low-density (LDL) and high-density (HDL) cholesterol directly with the densities of Alzheimer hallmarks--neuritic plaques (NP) and neurofibrillary tangles (NFT)--in nursing home residents (n=281). Results: Significant positive associations of TC and LDL with NP densities were found in both the neocortex (TC: r=0.151, p=0.013 and LDL: r=0.190, p=0.005) and the hippocampal/entorhinal (allocortical) region (TC: r=0.182, p=0.002 and LDL: r=0.203, p=0.003). Associations of HDL with NP were less strong but also significant. In contrast, after adjustment for confounders, no correlations of NFT with any lipid were significant.When subjects with any non-AD neuropathology (largely vascular) were excluded, the TC-plaque and LDL-plaque associations for the remaining “Pure AD” subgroup were consistently stronger than for the full sample. The TC- and LDL-plaque correlations were also stronger for the subgroup of 87 subjects with an APOE ε4 allele. Conclusions: The findings indicate that serum TC and LDL levels clearly relate to densities of NP, but not to densities of NFT. The stronger associations found in the subgroup that excluded all subjects with non-AD neuropathology suggest that cerebrovascular involvement does not explain these lipid-plaque relationships. Since the associations of TC/LDL with NP were particularly stronger in ε4 carriers, varying prevalence of this allele may explain some discrepancies among prior studies.