Despite these limitations, the present findings point to several intriguing extensions for follow-up. First, GWAS of longitudinal change in florbetapir PET Aβ burden is likely to elucidate additional genes modulating the rate of progression of AD neuropathology. Complementary analytical strategies, including pathway- and epistasis-based approaches, may also reveal functional influences on Aβ deposition that are not easily observed through standard GWAS methodologies. In addition, whole genome sequencing will dramatically enhance the granularity of coverage for GWAS-implicated loci and could be particularly valuable for discovering additional novel loci, rare variants, copy number variants, and DNA regulatory elements. Finally, the approval for widespread use of both florbetapir PET imaging and butyrylcholinesterase inhibitors creates a unique opportunity to prospectively assess the effects of these drugs on Aβ deposition over time, particularly among individuals at early stages in the AD spectrum where clinical efficacy would likely be most valuable.
